pubs.acs.

org/joc

One-Pot Conversions of Olefins to Cyclic Carbonates and Secondary

Allylic and Homoallylic Amines to Cyclic Carbamates
Stephen G. Davies,* Ai M. Fletcher, Wataru Kurosawa, James A. Lee, Giovanna Poce,
Paul M. Roberts, James E. Thomson, and David M. Williamson
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road,
Oxford OX1 3TA, U.K.

steve.davies@chem.ox.ac.uk
Received August 20, 2010

Sequential treatment of a 1,2-disubstituted olefin with m-CPBA, Br3CCO2H, and DBU results in the
one-pot, stereospecific conversion of the olefin to the corresponding disubstituted cyclic carbonate
(1,3-dioxolan-2-one). The reaction proceeds via an initial epoxidation followed by SN2-type epoxide
ring opening by Br3CCO2H and subsequent base-promoted carbonate formation upon elimination
of bromoform. When a solution of a secondary allylic or homoallylic amine and Br3CCO2H
is sequentially treated with m-CPBA then DBU, the product of the reaction is a cyclic carbamate
(1,3-oxazolidin-2-one or 1,3-oxazinan-2-one).

Introduction gas into an epoxide ring has been developed into an efficient
synthetic route.4
Cyclic carbonates are useful intermediates within organic
As part of an ongoing research program directed toward
synthesis1 and are often employed as protecting groups for
the chemo- and diastereoselective functionalization of allylic
1,2-diols.2 Interest in their synthesis has increased recently as
and homoallylic amines at the olefin,5 we have previously
they have been employed as polar aprotic solvents for a
developed an ammonium-directed olefinic oxidation of allylic
variety of reactions and as electrolytes for lithium ion
batteries.3 Methods for their preparation often rely on the
treatment of a 1,2-diol with phosgene (or an equivalent),2 (4) Coates, G. W.; Moore, D. R. Angew. Chem., Int. Ed. 2004, 43, 6618.
although more recently the metal-catalyzed insertion of CO2 Zhou, C.-H.; Beltramini, J. N.; Fana, Y. X.; Lu, G. Q. Chem. Soc. Rev. 2008,
37, 527.
(5) For examples of chemo- and diastereoselective cyclopropanations of
(1) Clements, J. H. Ind. Eng. Chem. Res. 2003, 42, 663. allylic amines from this laboratory, see: (a) Davies, S. G.; Ling, K. B.;
(2) Shaikh, A.-A. G.; Sivaram, S. Chem. Rev. 1996, 96, 951. Roberts, P. M.; Russell, A. J.; Thomson, J. E. Chem. Commun. 2007, 4029.
(3) Sch€
affner, B.; Sch€affner, F.; Verevkin, S. P.; B€
orner, A. Chem. Rev. (b) Csatayov a, K.; Davies, S. G.; Lee, J. A.; Ling, K. B.; Roberts, P. M.;
2010, 110, 4554. Russell, A. J.; Thomson, J. E. Tetrahedron 2010, 66, 8420.

DOI: 10.1021/jo101614f Published on Web 10/18/2010 J. Org. Chem. 2010, 75, 7745–7756 7745
r 2010 American Chemical Society
JOC Article Davies et al.

SCHEME 1a SCHEME 3a

a
Reagents and conditions: (i) Cl3CCO2H, m-CPBA, CH2Cl2, rt, 21 h,
then NaHCO3 (0.1 M, aq); (ii) K2CO3, MeOH, rt, 16 h.

SCHEME 2a

a
Reagents and conditions: (i) Cl3CCO2H, m-CPBA, CH2Cl2, rt, 21 h, a
Reagents and conditions: (i) Cl3CCO2H, m-CPBA, CH2Cl2, rt, 21 h,
then NaHCO3 (0.1 M, aq). then NaHCO3 (0.1 M, aq); (ii) Et3N, CH2Cl2, rt, 2 h; (iii) acid, m-CPBA,
CH2Cl2, rt, 18 h, then base, 0 °C to rt, 2 h (see table).
and homoallylic amines6 to facilitate the synthesis of amino
diol units.7 For instance, treatment of 3-N,N-dibenzylami-
nocyclohex-1-ene 1 with Cl3CCO2H followed by m-CPBA (i.e., those employed for 1, 4, and 5), oxidation of 8 resulted
and basic aqueous workup using NaHCO3 gave trichlo- in a 56:35:9 mixture of the regioisomeric trichloroacetate
roacetate ester 2 in 95:5 dr and quantitative yield. Tran- esters 9 and 10 and diol 11, with no trace of the correspond-
sesterification of 2 upon treatment with K2CO3 in MeOH ing cyclic carbonate 12. The absence of any cyclization
gives amino diol 3 in 95:5 dr and quantitative yield7a suggested that the presence of the amine function within 4
(Scheme 1). and 5 may have been important in promoting carbonate
Upon application of this protocol to bis- and trisho- formation. Indeed, when the mixture of trichloroacetate
moallylic amines 4 and 5 we noted that cyclic carbonates 6 esters 9 and 10 (and diol 11) was treated with Et3N in
and 7 were produced as the major products, rather than the CH2Cl2, conversion of both 9 and 10 to carbonate 12
expected trichloroacetate esters (Scheme 2).8 We were sur- occurred, and 12 was isolated in 52% yield after purification.
prised to note that this result represents only the second This transformation was next developed into a one-pot
reported example of the formation of a 1,3-dioxolan-2-one procedure for the formation of carbonate 12 from olefin 8:
upon treatment of an R-trichloroacetoxy alcohol with base9 the optimal protocol involved the treatment of allylbenzene 8
(in contrast, treatment of an R-trichloroacetamido alcohol with m-CPBA followed by Br3CCO2H, followed finally by
with base to form a 1,3-oxazolidin-2-one has been well the introduction of excess DBU to the reaction flask (as both
documented).10 In this light, we proposed that the transfor- a base and sacrificial reducing agent to scavenge any remain-
mation could be developed into a one-pot protocol for the ing peracid).11 These conditions proved more efficacious in
conversion of an olefin to a cyclic carbonate and delineate promoting carbonate formation than when employing either
herein the results of our studies in this area. F3CCO2H or Cl3CCO2H as the acid and/or than when
employing Et3N as both the reducing agent and base. No
Results and Discussion trihaloacetate ester products were observed in any of these
optimization studies, presumably due to in situ hydrolysis
One-Pot Conversion of Olefins to Cyclic Carbonates. The upon aqueous workup (Scheme 3).
application of our oxidation protocol to allylbenzene 8 (as a The mechanism and course of the reaction was followed by
model substrate) was examined. Under our literature conditions7a 1
H NMR spectroscopic analysis. Addition of m-CPBA to
allylbenzene 8 in CDCl3 promoted complete conversion of
starting material to epoxide 13 after 3 h. Subsequent addition
(6) We also developed a protocol for the diastereoselective oxidation of
the corresponding tertiary amine N-oxides; see: Aciro, C.; Davies, S. G.; of Br3CCO2H produced a 65:35 mixture of tribromoacetate
Kurosawa, W.; Roberts, P. M.; Russell, A. J.; Thomson, J. E. Org. Lett. esters 14 and 15 in quantitative conversion. When the
2009, 11, 1333. oxidation reaction was repeated using m-CPBA in the pres-
(7) (a) Aciro, C.; Claridge, T. D. W.; Davies, S. G.; Roberts, P. M.;
Russell, A. J.; Thomson, J. E. Org. Biomol. Chem. 2008, 6, 3751. (b) Aciro, C.; ence of Br3CCO2H, however, a reaction time of 7 h was
Davies, S. G.; Roberts, P. M.; Russell, A. J.; Smith, A. D.; Thomson, J. E. required before complete consumption of starting material
Org. Biomol. Chem. 2008, 6, 3762. (c) Bond, C. W.; Cresswell, A. J.; Davies,
S. G.; Kurosawa, W.; Lee, J. A.; Fletcher, A. M.; Roberts, P. M.; Russell, (to give a 65:35 mixture of tribromoacetate esters 14 and 15),
A. J.; Smith, A. D.; Thomson, J. E. J. Org. Chem. 2009, 74, 6735. (d) Bagal, indicating that the epoxidation reaction occurs faster in
S. K.; Davies, S. G.; Lee, J. A.; Roberts, P. M.; Russell, A. J.; Scott, P. M.; the absence of Br3CCO2H, presumably due to competitive
Thomson, J. E. Org. Lett. 2010, 12, 136.
(8) Although carbonate 7 could be isolated in pure form (84% yield), an
analytical sample of 6 could not be obtained even after exhaustive flash (10) For instance, see: Oishi, T.; Ando, K.; Inomiya, K.; Sato, H.; Iida,
column chromatography due to the presence of residual unidentified impu- M.; Chida, N. Org. Lett. 2002, 4, 151. Sakaguchi, H.; Tokuyama, H.;
rities (∼10%). Fukuyama, T. Org. Lett. 2007, 9, 1635. Shih, T.-L.; Li, H.-Y.; Ke, M.-S.;
(9) Bailey, S.; Helliwell, M.; Teerawutgulrag, A.; Thomas, E. J. Org. Kuo, W.-S. Synth. Commun. 2008, 38, 4139.
Biomol. Chem. 2005, 3, 3654. (11) Wefelscheid, U. K.; Woodward, S. J. Org. Chem. 2009, 74, 2254.

7746 J. Org. Chem. Vol. 75, No. 22, 2010

Davies et al.
JOC Article
SCHEME 4a SCHEME 6a

a
Reagents and conditions: (i) Br3CCO2H, m-CPBA, CDCl3, rt, 3 or
7 h; (ii) DBU, 0 °C to rt, 2 h.

SCHEME 5a

a
Reagents and conditions: (i) Br3CCO2H, CDCl3, rt, 12 h; (ii) K2CO3,
MeOH rt, 2 h.

hydrogen bonding of the carboxylic acid to the peracid dis- a

Reagents and conditions: (i) Br3CCO2H, m-CPBA, CH2Cl2, rt, 18 h,
rupting the intramolecularly hydrogen-bonded, reactive confor- then DBU, 0 °C to rt, 2 h.
mer of the latter.12 Subsequent addition of DBU promoted
complete conversion to carbonate 12, establishing that carbon-
ate formation occurs only upon basic workup. The obser- The optimized reaction conditions were applied to a range
vation that a 65:35 mixture of tribromoacetate esters 14 and of mono- and disubstituted olefins bearing a variety of functional
15 is formed in both of these reactions suggests that either the groups. In these reactions, m-CPBA was added to a solution
intermediate epoxide 13 does not undergo regioselective ring of the olefin in CH2Cl2 followed by the addition of Br3CCO2H,
opening or regioselective ring opening occurs followed by an except in the cases of unsaturated amines 5, 33, and 42, in
equilibration process (Scheme 4). To determine which of these which Br3CCO2H must be added first to prevent competing
mechanistic scenarios was in operation, enantiopure tetra- N-oxidation.7a In each case, conversion to the corresponding
dec-1-ene oxide (R)-16 (commercially available) was treated carbonate was observed. Carbonate formation from (Z)-olefins
with Br3CCO2H in CDCl3, which resulted in a 65:35 mixture 30-33 resulted in the corresponding trans-configured carbon-
of tribromoacetate esters 17 and 18, respectively. Transes- ates 34-37, while (E)-olefins 38-42 gave the corresponding
terification of this mixture upon treatment with K2CO3 in cis-configured carbonates 43-47, as single diastereoisomers.
MeOH gave the common diol 19 in 65:35 er,13 demonstrating These stereochemical assignments could be made confidently
that the ring opening of epoxide 16 occurs in a nonregiose- on the basis of 1H NMR NOE analyses of 34-37 and 43-47:
lective manner and hence results in erosion of the stereo- cis-configured carbonates (1,3-dioxolan-2-ones) 43-47 gave
chemical integrity of the final product 19 (Scheme 5); the strong reciprocal enhancements between C(4)H and C(5)H
observation of a 65:35 mixture of tribromoacetate esters 14 and between the C(4)- and C(5)-substituents (generally two
and 15 from the epoxidation and ring opening of allylben- methylene groups), while in the trans-configured compounds
zene 8 is therefore most likely also due to nonregioselective 34-37 strong reciprocal enhancements were noted between
ring opening of the intermediate epoxide 13 rather than an C(4)H and the C(5)-substituent and between the C(4)-sub-
equilibration process. stituent and C(5)H. The results from these experiments establish
that carbonate formation is a stereospecific (rather than
(12) Poluektov, P. T.; Gonsovskaya, T. B.; Ponomarev, F. G.; Gusev,
stereoselective) process, as would be expected for a mecha-
Y. K. Polym. Sci. USSR 1973, 15, 686. Bach, R. D.; Dmitrenko, O.; Adam, nism of formation involving epoxidation of the olefin, SN2-
W.; Schambony, S. J. Am. Chem. Soc. 2003, 125, 924. type epoxide ring opening, and cyclization upon basification
(13) The enantiomeric excess of diol 19 was determined by Chiral HPLC
analysis of the corresponding mono-p-nitrobenzoate derivative. For full via attack of the free hydroxyl group on the tribromoacetate
details see the Supporting Information. ester followed by loss of bromoform (Scheme 6).
J. Org. Chem. Vol. 75, No. 22, 2010 7747
JOC Article Davies et al.

SCHEME 7a of secondary bis- and trishomoallylic amines 4 and 5 which

gave carbonates 6 and 7, respectively, as the major products.
To investigate these observations further, secondary homo-
allylic amine 57 was sequentially treated with Cl3CCO2H
and m-CPBA followed by workup with aqueous NaHCO3
(i.e., under the conditions initially employed for oxidation of
4 and 5). This resulted in a mixture of products which
included carbamate 59 and carbonate 60 and as the major
components in an approximate 12:88 ratio, respectively.15
Purification via flash column chromatography gave carba-
mate 59 in 21% isolated yield and an impure sample of
carbonate 60 in ∼58% yield (the major impurity in this
sample was carbamate 59). The isolated yield of carbamate
59 (21%) was significantly higher than the proportion in-
dicated by analysis of the crude reaction mixture, suggesting
that carbonate 60 may undergo rearrangement to carbamate
59 during chromatography.16 Consistent with this hypothesis,
a sample of 60 in CDCl3 was observed by 1H NMR spectros-
copic analysis to rearrange to 59 over time; the rate of the
rearrangement process increased markedly in the presence of
triethylamine (Scheme 8).
a
Reagents and conditions: (i) Br3CCO2H, m-CPBA, CH2Cl2, rt, 18 h, These results offer some insight into the mechanism of
then DBU, 0 °C to rt, 2 h. formation of carbamate 59 upon sequential treatment with
Br3CCO2H, m-CPBA, and DBU, which was further investi-
SCHEME 8a gated by monitoring the reaction by 1H NMR spectroscopy.
Thus, a solution of homoallylic amine 57 and Br3CCO2H in
CDCl3 was treated with m-CPBA, which resulted in the
formation of an 87:13 mixture of tribromoacetate esters 62
and 63, respectively, with complete consumption of starting
material noted within 3 h. The appearance and disappear-
ance of an intermediate species was also observed; this
intermediate was tentatively assigned as being epoxide 61.
Addition of DBU to the reaction mixture resulted in the
immediate (<5 min) formation of a mixture of carbonate 60
(ca. 10%) and carbamate 59 (ca. 90%); within a further 2 h,
the major species present was carbamate 59 (>95%). A
general reaction pathway may therefore be proposed. Initial
a
Reagents and conditions: (i) Cl3CCO2H, m-CPBA, CH2Cl2, rt, 21 h, epoxidation of homoallylic amine 57 gives epoxide 61. Ring
then NaHCO3 (0.1 M, aq); (ii) stand in CDCl3. opening via an SN2-type process gives rise to a mixture of
regioisomeric tribromoacetate esters 62 and 63. Addition of
One-Pot Conversion of Secondary Allylic and Homoallylic
DBU to the reaction mixture results in deprotonation of
Amines to Oxazolidinones and Oxazinanones. When this
ammoniums 62 and 63 to reveal the nucleophilic nitrogen
procedure was applied to secondary allylic and homoallylic
atom within. Attack of the free amino group at the carbonyl
amines 48 and 49, the corresponding carbamates (oxazolidi-
within the conjugate base of 63 leads directly to the corre-
none 50 and oxazinanone 51, respectively) were produced as
sponding six-ring carbamate 59, although attack of the
the major products. Similarly, oxidation of secondary allylic
hydroxyl group onto the carbonyl group results in formation
amines 52 and 56 gave the diastereoisomeric oxazolidinones
of the five-membered carbonate 60. Direct formation of
54 and 58, while oxidation of secondary homoallylic amines
carbamate 59 from the conjugate base of 62 (the major
53 and 57 gave the diastereoisomeric oxazinanones 55 and 59
product of the oxidation reaction) is not possible and therefore
in good isolated yield and as single diastereoisomers in each
presumably proceeds via the initial formation of carbonate
case (Scheme 7). The relative configurations within 58 and 59
60. Subsequent rearrangement of carbonate 60 to carbamate
were unambiguously established by single-crystal X-ray
59 is driven by formation of the more thermodynamically
analyses.14 Therefore, given the diastereoisomeric nature of
favorable product (Scheme 9). Rearrangement of carbonates
54 and 58, and of 55 and 59, the relative configurations within
6 and 7, derived from bis- and trishomoallylic amines 4 and 5
54 and 55 could confidently be assigned and are consistent
in this manner, is presumably disfavored (e.g., through kinetic
with the reaction proceeding via an anti-dihydroxylation
event with respect to the double bond in each case. (15) The ratio of carbamate 59 to carbonate 60 was found to vary upon
The formation of carbamate products in these reactions is several runs of this reaction, and a sample of carbonate 60 was not always
in contrast to our initial observations concerning the oxidation isolated upon purification: conversion to carbamate 59 during purification
was assumed to be complete in these cases.
(16) O- to N-acyl migration has been previously reported. For instance,
(14) Crystallographic data (excluding structure factors) have been depos- see: Yakura, T.; Yoshimoto, Y.; Ishida, C.; Mabuchi, S. Tetrahedron 2007,
ited with the Cambridge Crystallographic Data Centre as supplementary 63, 4429. Yu, D.-S.; Xu, W.-X.; Liu, L.-X.; Huang, P.-Q. Synlett 2008, 1189.
publication numbers CCDC 784948 (58) and CCDC 784949 (59). Gonzalez-Gomez, J. C.; Foubelo, F.; Yus, M. J. Org. Chem. 2009, 74, 2547.

7748 J. Org. Chem. Vol. 75, No. 22, 2010

Davies et al.
JOC Article
SCHEME 9

SCHEME 10

retardation) due to the requirement to form a seven- or eight- SCHEME 11a

membered ring, respectively, thus accounting for the differ-
ences in reactivity in the oxidation reactions of unsaturated
amines 4, 5, and 57 carried out with m-CPBA in the presence
of Cl3CCO2H followed by workup with aqueous NaHCO3.
Analogous observations were made when the reaction of
allylic amine 52 was monitored by 1H NMR spectroscopy.
Addition of m-CPBA to a solution of 52 and Br3CCO2H in
CDCl3 resulted in the formation of epoxide 64 and tribro-
moacetate ester 65 as a single regioisomer;7 within 2 h
complete consumption of starting material was noted, and
within a further 4 h ring opening of the intermediate epoxide
64 to give tribromoacetate ester 65 had also reached comple-
tion. The observation of a single regioisomeric tribromoace-
tate ester 65 in this reaction is consistent with ring opening of
the intermediate epoxide 64 occurring at the carbon atom a
Reagents and conditions: (i) Et2Zn, CH2l2, F3CCO2H, CH2Cl2, rt, 1 h.
distal to the protonated N-benzyl amino moiety,7 where its
destabilizing inductive electron-withdrawing influence on in which 1,3-allylic strain is minimized (Scheme 11).5b Given
the late transition state is less pronounced.17 Addition of the excellent levels of substrate control elicited in these systems,
DBU to the reaction mixture gave a mixture of products, it was envisaged that application of our oxidation method-
although after 2 h the only species present was carbamate 54, ology to chiral allylic amines such as 67 and 68 would result
consistent with the conversion of tribromoacetate ester 65 to in a diastereoselective version of this protocol that would be
carbamate 54 occurring via initial formation of carbonate 66 applicable to the preparation of enantiopure carbonates:18
(Scheme 10). the protonated amino group has the capacity to effect hydrogen-
Diastereoselective Synthesis of Carbonates from Chiral bonded delivery of the oxidant and promote ring opening of
Allylic Amines. We have recently shown that the substrate- the so-formed epoxide distal to itself.7
directed cyclopropanation of tertiary allylic amines 67 and Oxidation of 67 and 68 with m-CPBA in the presence of
68 (having a stereogenic center at the allylic position) pro- Cl3CCO2H at room temperature gave complete conversion
ceeds with very high levels of diastereoselectivity to give the to the corresponding epoxides 73 and 74 in >99:1 dr in both
corresponding syn-cyclopropanes 70 and 71, consistent with cases. The relative configuration within 74 was established
the directed reaction proceeding via transition state model 69
(18) The preparation of enantiopure tertiary allylic amines (with struc-
(17) Parker, R. E.; Isaacs, N. S. Chem. Rev. 1959, 59, 737. Addy, J. K.; tures similar to 67 and 68) from R-amino acids has been demonstrated; see:
Parker, R. E. J. Chem. Soc. 1963, 915. Barluenga, J.; Baranga~na, B.; Concell
on, J. M. J. Org. Chem. 1995, 60, 6696.

J. Org. Chem. Vol. 75, No. 22, 2010 7749

JOC Article Davies et al.

SCHEME 12a SCHEME 13a

a
Reagents and conditions: (i) Cl3CCO2H, m-CPBA, CH2Cl2, rt, 1 h
(R = Ph) or 21 h (R = iPr); (ii) Br3CCO2H, CDCl3, rt, 12 h; (iii) DBU, a
Reagents and conditions: (i) Br3CCO2H, m-CPBA, CH2Cl2, rt, 3 days,
CDCl3, 0 °C to rt, 1 h; (iv) Br3CCO2H, m-CPBA CH2Cl2, rt, 18 h, then then DBU, 0 °C to rt, 2 h.
DBU, 0 °C to rt, 2 h; (v) Cl3CCO2H, m-CPBA, CH2Cl2, 40 °C, 21 h;
(vi) K2CO3, MeOH, 60 °C 16 h. unambiguously established by single-crystal X-ray analysis;21
diol 77 was also prepared directly from allylic amine 67 upon
unambiguously by single-crystal X-ray analysis,19 and the treatment with m-CPBA in the presence of Cl3CCO2H at
relative configuration within 73 was assigned by analogy. 40 °C followed by transesterification (K2CO3/MeOH), con-
The stereochemical outcomes of these oxidation reactions sistent with a mechanism involving completely diastereose-
are therefore consistent with an ammonium-directed process lective epoxidation followed by completely regioselective
proceeding via transition state model 72 in which 1,3-allylic ring opening (Scheme 12).
strain is minimized. Treatment of a sample of epoxide 73 in It is noteworthy that even in the absence of significant 1,3-
CDCl3 with Br3CCO2H revealed quantitative conversion to allylic strain it is possible to obtain modest levels of diastereo-
tribromoacetate ester 75 as a single regio- and diastereo- selectivity within systems similar in structure to tertiary
isomer within 12 h. The connectivity within 75 was estab- allylic amines 67 and 68. For example, under optimized
lished by 1H NMR COSY and HMBC analyses. Subsequent conditions, sequential treatment of tertiary allylic amine 78
treatment of 75 with DBU gave quantitative conversion to with Br3CCO2H and m-CPBA at rt for 3 days followed by
carbonate 76 within 1 h. Interestingly, under analogous DBU gave a chromatographically inseparable 85:15 mixture
conditions, epoxide 74 showed a distinct recalcitrance to of carbonates 82 and 83,22 which were isolated in 77%
undergo ring opening upon treatment with Br3CCO2H, and combined yield. The relative configuration within the major
the use of more forcing conditions resulted only in starting diastereoisomeric carbonate 82 was assigned upon the as-
material degradation. In light of these results, application of sumption that the reaction proceeds by an analogous mech-
our previously optimized one-pot protocol for the formation anism to that delineated for 67, via epoxidation transition
of carbonates from allylic amines was investigated for 67, state model 79 that places the allylic C-H bond (i.e., C(1)H)
although this was found to give a 2:1 mixture of epoxide 73 of 78 coplanar with the olefinic C-H bond (i.e., C(3)H) to
(>99:1 dr) and carbonate 76 (>99:1 dr); when the reaction minimize allylic 1,3-strain (i.e., directly analogous to transi-
was repeated using 10 equiv of Br3CCO2H to promote the tion state model 72) to give the major epoxide diastereo-
ring-opening reaction, complete conversion to carbonate 76 isomer 80. Ring opening of the epoxide via an SN2-type
(>99:1 dr) was observed, and 76 was isolated in 90% yield as process at the carbon atom distal to the ammonium moiety
a single diastereoisomer whose relative configuration was
unambiguously assigned by single-crystal X-ray analysis;20 (21) Crystallographic data (excluding structure factors) have been depos-
this analysis also affirmed the regioselectivity of the epoxide ited with the Cambridge Crystallographic Data Centre as supplementary
ring-opening reaction [i.e., that formation of tribromoace- publication number CCDC 784952.
(22) The crude reaction mixture also contained an 85:15 mixture of diols
tate ester 75 from epoxide 73 occurs by preferential epoxide 84 and 85 (the ratio of carbonates 82 and 83 to diols 84 and 85 was 88:12);
ring opening distal to the ammonium moiety (as predicted) chromatography allowed isolation of the major diastereoisomeric diol 84 in
rather than via a process involving ring opening proximal to 7% yield and >99:1 dr, in addition to the 85:15 mixture of carbonates 82 and
83. The production of diols 84 and 85 in this reaction is presumably a result of
the ammonium moiety followed by migration of the tribro- competitive hydrolysis of the corresponding carbonates 82 and 83 or the
moacetate group]. Treatment of carbonate 76 with K2CO3 intermediate tribromoacetate esters. Treatment of an 85:15 mixture of
in MeOH gave diol 77 whose relative configuration was carbonates 82 and 83 with K2CO3 in MeOH gave an 85:15 mixture of diols
84 and 85.

(19) Crystallographic data (excluding structure factors) have been depos-

ited with the Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 784950.
(20) Crystallographic data (excluding structure factors) have been depos-
ited with the Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 784951.

7750 J. Org. Chem. Vol. 75, No. 22, 2010

Davies et al.
JOC Article
gives tribromoacetate ester 81, which undergoes elimination 0.1 M aq NaHCO3 (4  100 mL), dried, and concentrated in
of bromoform upon treatment with base to give carbonate 82 vacuo. Purification via flash column chromatography (eluent
as the major product (Scheme 13). EtOAc) gave 7 as a colorless oil (553 mg, 84%): νmax (film) 2937
(C-H), 1796 (CdO); δH (400 MHz, CDCl3) 1.36-1.45 (1H, m,
Conclusion C(20 )HA), 1.46-1.54 (1H, m, C(20 )HB), 1.54-1.61 (2H, m, C(30 )H2),
1.63-1.70 (1H, m, C(10 )HA), 1.71-1.82 (1H, m, C(10 )HB), 2.65
In conclusion, sequential treatment of a 1,2-disubstituted (2H, t, J 7.2, C(40 )H2), 3.79 (2H, s, NCH2Ph), 4.03 (1H, dd,
olefin with m-CPBA, Br3CCO2H, and DBU results in the J 8.3, 7.2, C(5)HA), 4.49 (1H, app t, J 8.3, C(5)HB), 4.63-4.71
one-pot, stereospecific conversion of the olefin to the corre- (1H, m, C(4)H), 7.23-7.35 (5H, m, Ph); δC (100 MHz, CDCl3)
sponding disubstituted cyclic carbonate (1,3-dioxolan-2- 22.2 (C(20 )), 29.0 (C(30 )), 33.7 (C(10 )), 48.5 (C(40 )), 53.5 (NCH2Ph),
69.3 (C(5)), 77.0 (C(4)), 127.3, 128.3, 128.5 (o,m,p-Ph), 139.1
one). The reaction proceeds via an initial epoxidation fol-
(i-Ph), 155.0 (C(2)); m/z (ESIþ) 250 ([M þ H]þ, 100%); HRMS
lowed by SN2-type epoxide ring opening by Br3CCO2H and (ESIþ) C14H20NO3þ requires 250.1438; found 250.1439.
subsequent base-promoted carbonate formation upon elim- Method B. Following general procedure 2, 5 (189 mg, 1.00
ination of bromoform. When a solution of a secondary mmol) in CH2Cl2 (6.7 mL) was treated with Br3CCO2H (1.48 g,
allylic or homoallylic amine and Br3CCO2H is sequentially 5.00 mmol) and m-CPBA (344 mg, 75%, 1.50 mmol) followed by
treated with m-CPBA then DBU, the product of the reaction DBU (2.0 mL). Purification via flash column chromatography
is a cyclic carbamate (1,3-oxazolidin-2-one or 1,3-oxazinan- (eluent EtOAc) gave 7 as a colorless oil (159 mg, 64%).
2-one). (RS)-4-Benzyl-1,3-dioxolan-2-one 12. Following general pro-
cedure 1, 8 (80.2 mg, 0.678 mmol) in CH2Cl2 (4.5 mL) was
Experimental Section treated with Br3CCO2H (1.00 g, 3.39 mmol) and m-CPBA (233 mg,
75%, 1.01 mmol) followed by DBU (1.0 mL). Purification via
General Experimental Details. m-CPBA was supplied as a flash column chromatography (eluent 40-60 °C petrol/EtOAc,
70-77% slurry in water and titrated according to the procedure 4:1) gave 12 as a colorless oil (101 mg, 84%):24 δH (400 MHz,
of Swern23 immediately before use. Water was purified by an CDCl3) 2.99 (1H, dd, J 14.0, 6.5, CHACHBPh), 3.15 (1H, dd,
Elix UV-10 system. Organic solvents were used as supplied J 14.0, 6.1, CHACHBPh), 4.17 (1H, dd, J 8.5, 6.8, C(5)HA), 4.44
(analytical or HPLC grade) without prior purification. Organic (1H, dd, J 8.5, 7.9, C(5)HB), 4.90-4.97 (1H, m, C(4)H),
layers were dried over MgSO4. Thin layer chromatography was 7.21-7.38 (5H, m, Ph).
performed on aluminum plates coated with 60 F254 silica. Plates Tetradecane-1,2-diol 19. Br3CCO2H (147 mg, 0.50 mmol) was
were visualized using UV light (254 nm), iodine, 1% aqueous added to a solution of (R)-1,2-epoxytetradecane 16 (21 mg, 0.10
KMnO4, or 10% ethanolic phosphomolybdic acid. Flash col- mmol) in CDCl3 (0.6 mL). The reaction was monitored by 1H
umn chromatography was performed either on Kieselgel 60 NMR analysis for 12 h. The reaction mixture was then diluted
silica on a glass column or on an automated flash column with CH2Cl2 (10 mL) and washed with satd aq Na2SO3 (10 mL),
chromatography platform. followed by satd aq NH4Cl (10 mL). The organic layer was dried
Melting points are uncorrected. IR spectra were recorded as and concentrated in vacuo. The residue was dissolved in MeOH
either a thin film on NaCl plates (film) or a KBr disk (KBr), as (2.0 mL). K2CO3 (138 mg, 1.0 mmol) was added, and the
stated. Selected characteristic peaks are reported in cm-1. NMR mixture was stirred at rt for 16 h and then concentrated in
spectra were recorded in the deuterated solvent stated. The field vacuo. The residue was dissolved in CH2Cl2 (10 mL) and washed
was locked by external referencing to the relevant deuteron with satd aq NaHCO3 (10 mL) and brine (10 mL). The organic
resonance. 1H-1H COSY and 1H-13C HMQC analyses were layer was dried and concentrated in vacuo to give 19 as white
used to establish atom connectivity. solid (20.0 mg, 87%, 65:35 er):25 mp 60-62 °C {lit.25 mp 62-
General Procedure 1 for Oxidation of Olefins. m-CPBA was 64 °C}; δH (400 MHz, CDCl3) 0.88 (3H, t, J 7.0, CH3), 1.19-
added to a stirred solution of olefin in CH2Cl2, and the resultant 1.45 (22H, m, CH2), 3.25-3.35 (1H, m, C(1)HA), 3.65-3.78
mixture was stirred at rt for 10 min. Br3CCO2H was added in one (2H, m, C(1)HB, C(2)H).
portion, and the reaction mixture was stirred at rt for 18 h. DBU The enantiomeric excess of 19 was determined by Chiral
was added at 0 °C, and the resultant mixture was stirred at rt for HPLC of the corresponding mono-p-nitrobenzoate derivative,
2 h. Satd aq NaHCO3 and CH2Cl2 were added, and the layers were giving resolution of both enantiomers: OD-H Daicel chiral
separated. The organic layer was washed with satd aq NaHCO3 column, flow rate 1.5 mL/min (iso-propanol/hexane 3:97), (S)-
and brine and then dried, filtered, and concentrated in vacuo. enantiomer tR = 17.1 min and (R)-enantiomer tR = 22.7 min.
General Procedure 2 for Oxidation of Unsaturated Amines. Data for 2-hydroxytetradecyl 4-nitrobenzoate: p-Nitroben-
Br3CCO2H was added to a stirred solution of olefin in CH2Cl2, zoyl chloride (80 mg, 0.43 mmol) was added to a solution of diol
and the resultant mixture was stirred at rt for 10 min. m-CPBA 19 (20 mg, 0.09 mmol) in pyridine (1.0 mL) and CH2Cl2 (1.0
was added in one portion, and the reaction mixture was stirred mL). The reaction mixture was stirred at rt for 8 h, diluted with
at rt for 18 h. DBU was added at 0 °C, and the resultant mixture CH2Cl2 (10 mL), and washed with satd aq CuSO4 (10 mL) and
was stirred at rt for 2 h. Satd aq NaHCO3 and CH2Cl2 were brine (10 mL). Purification via flash column chromatography
added, and the layers were separated. The organic layer was (eluent 40-60 °C petrol/EtOAc 8:1) gave 2-hydroxytetradecyl
washed with satd aq NaHCO3 and brine and then dried, filtered, 4-nitrobenzoate as a white solid (17 mg, 53%): mp 63-65 °C;
and concentrated in vacuo. νmax (KBr) 3475 (O-H), 2955 (C-H), 1697 (CdO), 1543; δH
(RS)-4-(40 -N-Benzylaminobutyl)-1,3-dioxolan-2-one 7. Method (400 MHz, CDCl3) 0.88 (3H, t, J 7.0, CH3), 1.19-1.38 (20H, m,
A. Cl3CCO2H (2.13 g, 13.2 mmol) was added to 5 (500 mg, CH2), 1.57-1.59 (2H, m, C(3)H2), 4.01-4.02 (1H, m, C(2)H),
2.64 mmol) in CH2Cl2 (5 mL) at rt, and the solution was stirred 4.28 (1H, dd, J 11.5, 7.1, C(1)HA), 4.43 (1H, dd, J 11.5, 3.0,
for 30 min. m-CPBA (985 mg, 75%, 4.22 mmol) was added, and C(1)HB), 8.22 (2H, d, J 8.8, Ar), 8.30 (2H, d, J 8.8, Ar); δC (100
the resultant solution was stirred at rt for 21 h. The mixture was MHz, CDCl3) 14.1 (C(14)), 22.6, 25.4, 29.1, 29.3, 29.5, 29.6,
then diluted with CH2Cl2 (100 mL) and washed with satd aq 29.7, 31.9, 33.5 (C(3)-C(13)), 69.9 (C(2)), 70.0 (C(1)), 123.6,
Na2SO3 (100 mL portions) until starch-iodide paper indicated that
no m-CPBA was present. The organic layer was then washed with
(24) Paddock, R. L.; Hiyama, Y.; McKay, J. M.; Nguyen, S. T. Tetra-
hedron Lett. 2004, 45, 2023.
(23) Swern, D. Org. React. 1953, VII, 392. (25) Kawashima, M.; Horikawa, Y. Biotechnol. Lett. 1993, 15, 1039.

J. Org. Chem. Vol. 75, No. 22, 2010 7751

JOC Article Davies et al.

130.8, 135.3 (o,m,p-Ar), 150.6 (i-Ar), 164.8 (CdO); m/z (ESIþ) 76.7 (C(40 )), 155.0 (C(20 )), 173.6 (C(1)); m/z (ESIþ) 225 ([M þ
402 ([M þ Na]þ, 90%); HRMS (ESIþ) C21H33NNaO5þ ([M þ Na]þ, 100%); HRMS (ESIþ) C9H14NaO5þ ([M þ Na]þ) requires
Na]þ) requires 402.2251; found 402.2252. 225.0733; found 225.0732.
(RS)-4-Phenyl-1,3-dioxolan-2-one 25. Following general (RS,RS)-4-Butyl-5-methyl-1,3-dioxolan-2-one 34. Following
qprocedure 1, 20 (105 mg, 1.00 mmol) in CH2Cl2 (6.7 mL) was general procedure 1, 30 (72 mg, 0.72 mmol) in CH2Cl2 (4.8 mL)
treated with Br3CCO2H (1.48 g, 5.00 mmol) and m-CPBA (344 was treated with Br3CCO2H (1.06 g, 3.61 mmol) and m-CPBA
mg, 75%, 1.50 mmol), followed by DBU (1.0 mL). Purification (250 mg, 75%, 1.08 mmol), followed by DBU (1.0 mL). Purifi-
via flash column chromatography (eluent 40-60 °C petrol/ cation via flash column chromatography (eluent 40-60 °C
EtOAc, 4:1) gave 25 as a colorless oil (103 mg, 63%):26 δH petrol/EtOAc, 5:1) gave 34 as a colorless oil (93 mg, 81%, >99:1 dr):
(400 MHz, CDCl3) 4.36 (1H, app t, J 8.4, C(5)HA), 4.81 (1H, app νmax (film) 2959 (C-H), 1802 (CdO); δH (400 MHz, CDCl3)
t, J 8.4, C(5)HB), 5.69 (1H, app t, J 8.4, C(4)H), 7.21-7.38 (5H, 0.89 (3H, t, J 6.5, C(40 )H3), 1.30-1.40 (4H, m, C(20 )H2, C(30 )H2),
m, Ph). 1.42 (3H, d, J 6.1, C(5)Me), 1.59-1.77 (2H, m, C(10 )H2), 4.16
(RS)-4-Decyl-1,3-dioxolan-2-one 26. Following general pro- (1H, dt, J 6.9, 5.1, C(4)H), 4.36 (1H, dq, J 6.9, 6.1, C(5)H); δC
cedure 1, 21 (151 mg, 0.90 mmol) in CH2Cl2 (6 mL) was treated (100 MHz, CDCl3) 13.7 (C(40 )), 19.0 (C(5)Me), 22.2 (C(20 )), 26.7
with Br3CCO2H (1.33 g, 4.50 mmol) and mCPBA (309 mg, 75%, (C(30 )), 32.8 (C(10 )), 78.4 (C(5)), 83.5 (C(4)), 154.6 (C(2)); m/z
1.35 mmol), followed by DBU (1.5 mL). Purification via flash (ESIþ) 181 ([M þ Na]þ, 100%); HRMS (ESIþ) C8H14NaO3þ
column chromatography (eluent 40-60 °C petrol/EtOAc 5:1) ([M þ Na]þ) requires 181.0835; found 181.0836.
gave 26 as a colorless oil (160 mg, 78%): νmax (film) 2925 (C-H), (RS,RS)-4-(Benzyloxymethyl)-5-propyl-1,3-dioxolan-2-one 35.
1800 (CdO), 1065; δH (400 MHz, CDCl3) 0.86 (3H, t, J 6.9, Following general procedure 1, 31 (190 mg, 1.00 mmol) in CH2Cl2
C(100 )H3), 1.22-1.36 (15H, m, CH2), 1.42-1.50 (1H, m, C(20 )- (6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol) and m-
HA), 1.67-1.69 (1H, m, C(10 )HA), 1.77-1.89 (1H, m, C(10 )HB), CPBA (344 mg, 75%, 1.50 mmol), followed by DBU (1.5 mL).
4.07 (1H, t, J 8.5, C(5)HA), 4.52 (1H, t, J 8.5, C(5)HB), 4.67-4.72 Purification via flash column chromatography (eluent 40-60 °C
(1H, m, C(4)H); δC (100 MHz, CDCl3) 14.1 (C(100 )), 22.6, 24.3, petrol/EtOAc, 4:1) gave 35 as a colorless oil (185 mg, 74%,
29.1, 29.2, 29.3, 29.4, 29.5, 31.8 (C(20 )-C(90 )), 33.9 (C(10 )), 69.4 >99:1 dr): νmax (film) 2962 (C-H), 1797 (CdO); δH (500 MHz,
(C(4)), 76.7 (C(5)), 155.6 (C(2)); m/z (ESIþ) 251 ([M þ Na]þ, CDCl3) 0.96 (3H, t, J 7.0, C(300 )H3), 1.38-1.44 (1H, m, C(200 )HA),
100%); HRMS (ESIþ) C13H24NaO3þ ([M þ Na]þ) requires 1.57-1.66 (2H, m, C(200 )HB, C(100 )HA), 1.79-1.85 (1H, m,
251.1618; found 251.1616. C(100 )HB), 3.64-3.71 (2H, m, CH2OBn), 4.57-4.58 (2H, m,
(RS)-4-(Benzyloxymethyl)-1,3-dioxolan-2-one 27. Following OCH2Ph), 4.70-4.73 (2H, m, C(4)H, C(5)H), 7.30-7.45 (5H,
general procedure 1, 22 (107 mg, 0.72 mmol) in CH2Cl2 (4.8 mL) m, Ph); δC (125 MHz, CDCl3) 13.7 (C(300 )H3), 19.2 (C(200 )), 30.5
was treated with Br3CCO2H (1.06 g, 3.60 mmol) and m-CPBA (C(100 )), 66.7 (CH2OBn), 73.8 (CH2Ph), 76.7, 79.2 (C(4), C(5)),
(506 mg, 75%, 2.19 mmol), followed by DBU (1.0 mL). Purification 127.7, 128.0, 128.5 (o,m,p-Ph), 137.0 (i-Ph), 154.5 (C(2)); m/z
via flash column chromatography (eluent 40-60 °C petrol/EtOAc, (ESIþ) 273 ([M þ Na]þ, 90%); HRMS (ESIþ) C14H18NaO4þ
4:1) gave 27 as a colorless oil (94 mg, 63%):27 δH (400 MHz, ([M þ Na]þ) requires 273.1097; found 273.1095.
CDCl3) 3.62 (1H, dd, J 11.0, 3.7, CHAHBOBn), 3.71 (1H, dd, J (RS,RS)-5-(20 -Hydroxyethyl)-4-ethyl-1,3-dioxolan-2-one 36.
11.0, 3.7, CHAHBOBn), 4.38 (1H, dd, J 8.6, 6.2, C(5)HA), 4.48 Following general procedure 1, 32 (100 mg, 1.00 mmol) in
(1H, app t, J 8.6, C(5)HB), 4.58 (2H, AB system, J 12.2, OCH2Ph), CH2Cl2 (6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00
4.79-4.84 (1H, m, C(4)H), 7.30-7.40 (5H, m, Ph). mmol) and m-CPBA (344 mg, 75%, 1.50 mmol), followed by
(RS)-4-(40 -Acetoxybutyl)-1,3-dioxolan-2-one 28. Following DBU (1.0 mL). Purification via flash column chromatography
general procedure 1, 23 (70 mg, 0.50 mmol) in CH2Cl2 (3.3 mL) (eluent 40-60 °C petrol/EtOAc, 1:1) gave 36 as a pale yellow oil
was treated with Br3CCO2H (740 mg, 2.5 mmol) and m-CPBA (83 mg, 65%, >99:1 dr): νmax (film) 3424 (O-H), 2972 (C-H),
(172 mg, 75%, 0.75 mmol), followed by DBU (1.0 mL). Purifi- 1790 (CdO); δH (400 MHz, CDCl3) 1.02 (3H, t, J 7.5, Me), 1.74
cation via flash column chromatography (eluent 40-60 °C (2H, q, J 7.5, C(100 )H2), 1.91-1.98 (2H, m, C(10 )H2), 3.78-3.81
petrol/EtOAc, 1:1) gave 28 as an opaque oil (85 mg, 84%): νmax (2H, m, C(20 )H2), 4.30 (1H, dd, J 12.6, 7.5, C(5)H), 4.47-4.52
(film) 2917 (C-H), 1793 (CdO, carbonate), 1731 (CdO, ester); (1H, m, C(4)H); δC (100 MHz, CDCl3) 8.8 (C(200 )), 26.5 (C(100 )),
δH (400 MHz, CDCl3) 1.41-1.50 (1H, m, CH2), 1.53-1.61 (1H, 36.2 (C(10 )), 57.9 (C(20 )), 79.1 (C(4)), 83.4 (C(5)), 155.0 (C(2));
m, CH2), 1.66-1.76 (4H, m, CH2), 2.04 (3H, s, COMe), 4.05- m/z (ESIþ) 183 ([M þ Na]þ, 100%); HRMS (ESIþ) C7H12NaO4þ
4.08 (3H, m, C(5)HA, C(40 )H2), 4.53 (1H, t, J 9.4, C(5)HB), ([M þ Na]þ) requires 180.0628; found 180.0636.
4.47-4.74 (1H, m, C(4)H); δC (100 MHz, CDCl3) 20.9 (Me), (RS,RS)-4-(20 -Dibenzylaminoethyl)-5-ethyl-1,3-dioxolan-2-one
21.1, 28.1, 33.5 (C(10 )-C(30 )), 63.7 (C(40 )), 69.3 (C(5)), 76.8 37. Following general procedure 2, 33 (279 mg, 1.00 mmol) in
(C(4)), 154.9 (C(2)), 171.1 (COMe); m/z (ESIþ) 225 ([M þ Na]þ, CH2Cl2 (6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol)
100%); HRMS (ESIþ) C9H14NaO5þ ([M þ Na]þ) requires and m-CPBA (344 mg, 75%, 1.5 mmol), followed by DBU (1.0 mL).
225.0733; found 225.0732. Purification via flash column chromatography (eluent 40-60 °C
(RS)-Methyl 5-(10 ,30 -dioxolan-20 -one-40 -yl)pentanoate 29. petrol/EtOAc, 6:1) gave 37 as a colorless oil (252 mg, 74%,
Following general procedure 1, 24 (142 mg, 1.00 mmol) in CH2Cl2 >99:1 dr): νmax (film) 2969 (C-H), 1801 (CdO); δH (500 MHz,
(6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol) and m- CDCl3) 0.98 (3H, t, J 7.4, C(200 )H3), 1.46-1.58 (2H, m, C(100 )H2),
CPBA (344 mg, 75%, 1.50 mmol), followed by DBU (1.0 mL). 1.71-1.86 (1H, m, C(10 )HA), 1.88-1.94 (1H, m, C(10 )HB), 2.59-
Purification via flash column chromatography (eluent 40-60 °C 2.63 (2H, m, C(20 )H2), 3.61 (4H, AB system, JAB 13.5, N(CH2-
petrol/EtOAc, 2:1) gave 29 as a yellow oil (143 mg, 71%): νmax Ph)2), 4.05-4.09 (1H, m, C(5)H), 4.28-4.32 (1H, m, C(4)H),
(film) 2917 (C-H), 1793 (CdO, carbonate), 1731 (CdO, ester); 7.26-7.34 (10H, m, Ph); δC (125 MHz, CDCl3) 8.9 (C(200 )H3),
δH (400 MHz, CDCl3) 1.38-1.59 (2H, m, C(4)H2), 1.64-1.86 26.5 (C(100 )H2), 31.9 (C(10 )), 49.0 (C(20 )), 58.8 (N(CH2Ph)2), 79.8
(4H, m, C(3)H2, C(5)H2), 2.32 (2H, t, J 7.2, C(2)H2), 3.65 (3H, s, (C(5)), 82.8 (C(4)), 127.1, 128.4, 128.8 (o,m,p-Ph), 139.0 (i-Ph),
OMe), 4.05 (1H, dd, J 10.8, 7.2, C(50 )HA), 4.52 (1H, dd, J 10.8, 154.7 (C(2)); m/z (ESIþ) 362 ([M þ Na]þ, 100%); HRMS (ESIþ)
8.4, C(50 )HB), 4.66-4.73 (1H, m, C(40 )H); δC (100 MHz, CDCl3) C21H26NO3þ ([M þ H]þ) requires 340.1907; found 340.1911.
23.9, 24.3 (C(3), C(4), C(5)), 33.5 (C(2)), 51.6 (OMe), 69.3 (C(50 )), (RS,SR)-4-Butyl-5-methyl-1,3-dioxolan-2-one 43. Following
general procedure 1, 38 (71 mg, 0.72 mmol) in CH2Cl2 (4.8 mL)
(26) Kim, Y. J.; Barma, R. S. J. Org. Chem. 2005, 70, 7882.
was treated with Br3CCO2H (1.06 g, 3.61 mmol) and m-CPBA
(27) Matsumoto, K.; Fuwa, S.; Shimojo, M.; Kitajima, H. J. Chem. Soc. (250 mg, 75%, 1.08 mmol), followed by DBU (1.0 mL).
Jpn. 1996, 69, 2977. Purification via flash column chromatography (eluent 40-60 °C

7752 J. Org. Chem. Vol. 75, No. 22, 2010

Davies et al.
JOC Article
petrol/EtOAc, 5:1) gave 43 as a colorless oil (105 mg, 92%, 49.7 (C(20 )), 58.9 (N(CH2Ph)2), 77.8 (C(5)), 80.3 (C(4)), 127.3,
>99:1 dr): νmax (film) 2959 (C-H), 1799 (CdO); δH (400 MHz, 128.2, 129.7 (o,m,p-Ph), 139.0 (i-Ph), 154.6 (C(2)); m/z (ESIþ)
CDCl3) 0.93 (3H, t, J 7.2, C(40 )H3), 1.36 (3H, d, J 6.7, C(5)Me), 362 ([M þ Na]þ, 100%); HRMS (ESIþ) C21H26NO3þ ([M þ H]þ)
1.35-1.44 (4H, m, C(20 )H2, C(30 )H2), 1.51-1.57 (1H, m, requires 340.1907; found 340.1911.
C(10 )HA), 1.67-1.77 (1H, m, C(10 )HB), 4.63 (1H, ddd, J 10.2, (RS)-N(3)-Benzyl-5-(hydroxymethyl)-1,3-oxazolidin-2-one 50.
7.0, 3.4, C(4)H), 4.83 (1H, dq, 7.0, 6.7, C(5)H); δC (100 MHz, Following general procedure 2, 48 (147 mg, 1.00 mmol) in CH2Cl2
CDCl3) 13.8 (C(40 )), 14.5 (C(5)Me), 22.3 (C(20 )), 27.6 (C(30 )), (6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol) and
28.5 (C(10 )), 76.0 (C(5)), 80.0 (C(4)), 154.7 (C(2)); m/z (ESIþ) 181 m-CPBA (344 mg, 75%, 1.50 mmol), followed by DBU (2.0 mL).
([M þ Na]þ, 100%); HRMS (ESIþ) C8H14NaO3þ ([M þ Na]þ) Purification via flash column chromatography (gradient elution,
requires 181.0835; found 181.0831. 50%f100% EtOAc in 30-40 °C petrol) gave 50 as a colorless
(RS,SR)-4-Phenyl-4-methyl-1,3-dioxolan-2-one 44. Following oil (157 mg, 88%): νmax (film) 3408 (O-H), 2924, 2874 (C-H),
general procedure 1, 39 (118 mg, 1.00 mmol) in CH2Cl2 (6.6 mL) 1731 (CdO); δH (400 MHz, CDCl3) 3.35 (1H, app t, J 8.6,
was treated with Br3CCO2H (1.48 g, 5.00 mmol) and m-CPBA C(4)HA), 3.42 (1H, app t, J 8.6, C(4)HB), 3.57 (1H, dd, J 12.5,
(344 mg, 75%, 1.50 mmol), followed by DBU (1.2 mL). Purifica- 4.3, C(10 )HA), 3.78 (1H, dd, J 12.5, 3.2, C(10 )HB), 4.36 (2H, AB
tion via flash column chromatography (eluent 40-60 °C petrol/ system, JAB 15.0, NCH2Ph), 4.53-4.57 (1H, m, C(5)H), 7.25-
EtOAc, 5:1) gave 44 as a colorless oil (157 mg, 88%, >99:1 dr): 7.33 (5H, m, Ph); δC (100 MHz, CDCl3) 45.2 (C(4)), 48.2
νmax (film) 2984, 2936 (C-H), 1806 (CdO); δH (400 MHz, (NCH2Ph), 62.8 (C(10 )), 73.8 (C(5)), 127.9, 128.0, 128.8 (o,m,
CDCl3) 1.54 (3H, dt, J 6.1, 1.5, C(5)Me), 4.56-4.64 (1H, m, p-Ph), 135.6 (i-Ph), 158.3 (C(2)); m/z (ESIþ) 230 ([M þ Na]þ,
C(5)H), 5.14 (1H, d, J 8.1, C(4)H), 7.34-7.37 (2H, m, Ph), 100%); HRMS (ESIþ) C11H13NNaO3þ ([M þ Na]þ) requires
7.41-7.44 (3H, m, Ph); δC (100 MHz, CDCl3) 18.3 (C(5)Me), 230.0788; found 230.0788.
80.8 (C(5)), 84.9 (C(4)), 126.0, 129.1, 129.7 (o,m,p-Ph), 135.0 (RS)-N(3)-Benzyl-6-(hydroxymethyl)-1,3-oxazinan-2-one 51.
(i-Ph), 154.3 (C(2)); m/z (ESIþ) 201 ([M þ Na]þ, 100%); HRMS Following general procedure 2, 49 (100 mg, 0.620 mmol) in
(ESIþ) C10H10NaO3þ ([M þ Na]þ) requires 201.0522; found CH2Cl2 (4.1 mL) was treated with Br3CCO2H (917 mg, 3.10
201.0524. mmol) and m-CPBA (213 mg, 75%, 0.93 mmol), followed by
(RS,SR)-4-(Benzyloxymethyl)-5-propyl-1,3-dioxolan-2-one 45. DBU (1.0 mL). Purification via flash column chromatography
Following general procedure 1, 40 (190 mg, 1.00 mmol) in CH2Cl2 (gradient elution, 50%f100% EtOAc in 30-40 °C petrol)
(6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol) and gave 51 as a pale yellow solid (83 mg, 61%): mp 95-97 °C;
m-CPBA (344 mg, 75%, 1.50 mmol), followed by DBU (1.5 mL). νmax (KBr) 3384 (O-H), 2928, 2872 (C-H), 1672 (CdO); δH
Purification via flash column chromatography (eluent 40-60 °C (400 MHz, CDCl3) 1.89-2.17 (2H, m, C(5)H2), 3.20-3.23
petrol/EtOAc, 4:1) gave 45 as a colorless oil (178 mg, 71%, (1H, m, C(4)HA), 3.28-3.31 (1H, ddd, J 16.7, 11.5, 5.3,
>99:1 dr): νmax (film) 2959 (C-H), 1793 (CdO), 1051; δH (500 C(4)HB), 3.67 (1H, dd, J 12.3, 5.2, C(10 )HA), 3.83 (1H, dd, J
MHz, CDCl3) 0.97 (3H, t, J 7.0, C(300 )H3), 1.38-1.44 (2H, m, 12.3, 3.4, C(10 )HB), 4.34-4.38 (1H, m, C(6)H), 4.55 (2H, AB
C(200 )H2), 1.60-1.70 (1H, m, C(100 )HA), 1.70-1.80 (1H, m, system, JAB 14.9, NCH2Ph), 7.26-7.50 (5H, m, Ph); δC (100
C(100 )HB), 3.60 (1H, dd, J 10.9, 1.9, C(10 )HA), 3.68 (1H, dd, MHz, CDCl3) 23.4 (C(5)), 43.6 (C(4)), 52.6 (NCH2Ph), 64.3
J 10.9, 1.9, C(10 )HB), 4.34-4.37 (1H, m, C(4)H), 4.52-4.61 (3H, (CH2OH), 77.7 (C(6)), 127.7, 128.0, 128.7 (o,m,p-Ph), 136.4
m, OCH2Ph, C(5)H), 7.30-7.44 (5H, m, Ph); δC (125 MHz, (i-Ph), 153.8 (C(2)); m/z (ESIþ) 244 ([M þ Na]þ, 100%); HRMS
CDCl3) 13.6 (C(300 )), 17.8 (C(200 )), 36.0 (C(100 )), 68.7 (CH2OBn), (ESIþ) C12H15NNaO3þ ([M þ Na]þ) requires 244.0944; found
73.7 (OCH2Ph), 78.6 (C(5)), 79.9 (C(4)), 127.7, 128.0, 128.6 (o, 244.0943.
m,p-Ph), 137.0 (i-Ph), 154.5 (C(2)); m/z (ESIþ) 273 ([M þ Na]þ, (RS,SR)-N(3)-Benzyl-5-(10 -hydroxybutyl)-1,3-oxazolidin-2-one
100%); HRMS (ESIþ) C14H18NaO4þ ([M þ Na]þ) requires 54. Following general procedure 2, 52 (100 mg, 0.528 mmol) in
273.1097; found 273.1095. CH2Cl2 (3.5 mL) was treated with Br3CCO2H (778 mg, 2.64 mmol)
(RS,SR)-4-(20 -Hydroxyethyl)-5-ethyl-1,3-dioxolan-2-one 46. and m-CPBA (181 mg, 75%, 0.79 mmol), followed by DBU (1.0
Following general procedure 1, 41 (100 mg, 1.00 mmol) in CH2Cl2 mL). Purification via flash column chromatography (gradient
(6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol) and m- elution, 50%f100% EtOAc in 30-40 °C petrol) gave 54 as a
CPBA (344 mg, 75%, 1.50 mmol), followed by DBU (1.5 mL). colorless oil (113 mg, 86%, >99:1 dr): νmax (film) 3418 (O-H),
Purification via flash column chromatography (eluent 40-60 °C 2957 (C-H), 1726 (CdO); δH (400 MHz, CDCl3) 0.91 (3H, app
petrol/EtOAc, 1:1) gave 46 as a colorless oil (88 mg, 55%, >99:1 t, J 7.0, C(40 )H3), 1.31-1.38 (3H, m, C(20 )H2, C(30 )HA), 1.51-
dr): νmax (film) 3417 (O-H), 2974 (C-H), 1792 (CdO); δH (400 1.55 (1H, m, C(30 )HB), 3.32 (1H, t, J 8.7, C(4)HA), 3.45-3.47
MHz, CDCl3) 1.08 (3H, t, J 7.6, C(200 )H3), 162-1.72 (2H, m, (1H, m, C(4)HB), 3.86-3.89 (1H, m, C(10 )H), 4.33 (1H, d, J 14.9,
C(100 )H2), 1.73-1.92 (2H, m, C(10 )H2), 3.79-3.87 (2H, m, NCHAHBPh), 4.40 (1H, ddd, J 16.3, 8.7, 3.7, C(5)H), 4.52 (1H,
C(20 )H2), 4.59-4.65 (1H, m, C(4)H), 4.90-4.96 (1H, m, C(5)H); d, J 14.9, NCHAHBPh), 7.23-7.50 (5H, m, Ph); δC (100 MHz,
δC (100 MHz, CDCl3) 10.0 (C(200 )), 22.4 (C(100 )), 31.3 (C(10 )), CDCl3) 13.9 (C(40 )), 18.6 (C(30 )), 33.5 (C(20 )), 44.0 (C(4)), 48.3
58.4 (C(20 )), 76.7 (C(4)), 81.2 (C(5)), 154.7 (C(2)); m/z (ESIþ) 183 (NCH2Ph), 70.4 (C(10 )), 75.7 (C(5)), 127.9, 128.1, 128.8 (o,m,p-
([M þ Na]þ, 100%); HRMS (ESIþ) C7H12NaO4þ ([M þ Na]þ) Ph), 135.6 (i-Ph), 158.0 (C(2)); m/z (ESIþ) 272 ([M þ Na]þ,
requires 183.0628; found 183.0629. 100%); HRMS (ESIþ) C14H19NNaO3þ ([M þ Na]þ) requires
(RS,SR)-4-(20 -Dibenzylaminoethyl)-5-ethyl-1,3-dioxolan-2-one 272.1257; found 272.1254.
47. Following general procedure 2, 42 (279 mg, 1.00 mmol) in (RS,SR)-N(3)-Benzyl-6-(10 -hydroxypropyl)-1,3-oxazinan-2-one
CH2Cl2 (6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 55. Following general procedure 2, 53 (120 mg, 0.630 mmol) in
mmol) and m-CPBA (344 mg, 75%, 1.5 mmol), followed by CH2Cl2 (4.1 mL) was treated with Br3CCO2H (932 mg, 3.15
DBU (1.5 mL). Purification via flash column chromatography mmol) and m-CPBA (216 mg, 75%, 0.95 mmol), followed by
(eluent 40-60 °C petrol/EtOAc, 6:1) gave 47 as a colorless oil DBU (1.0 mL). Purification via flash column chromatography
(270 mg, 79%, >99:1 dr): νmax (film) 2971, 2803 (C-H), 1798 (gradient elution, 50%f100% EtOAc in 30-40 °C petrol) gave
(CdO); δH (500 MHz, CDCl3) 0.95 (3H, t, J 7.3, C(200 )H3), 55 as a colorless oil (138 mg, 88%, >99:1 dr): C14H19NO3
1.30-1.35 (1H, m, C(100 )HA), 1.50-1.57 (1H, m, C(100 )HB), 1.67- requires C, 67.45; H, 7.7; N, 5.6%; found C, 67.5; H, 7.6; N,
1.69 (1H, m, C(10 )HA), 1.80-1.85 (1H, m, C(10 )HB), 2.57-2.68 5.4%; νmax (film) 3392 (O-H), 3030 (C-H), 2966 (C-H), 1672
(2H, m, C(20 )H2), 3.61 (4H, br s, N(CH2Ph)2), 4.26-4.30 (1H, (CdO); δH (400 MHz, CDCl3) 1.02 (3H, t, J 5.5, C(30 )H3),
m, C(5)H), 4.72-4.76 (1H, m, C(4)H), 7.26-7.34 (10H, m, Ph); 1.45-1.56 (2H, m, C(20 )H 2), 1.89-2.05 (2H, m, C(5)H 2),
δC (125 MHz, CDCl3) 9.96 (C(200 )), 22.2 (C(100 )), 27.0 (C(10 )), 3.18-3.25 (2H, m, C(4)H2), 3.73 (1H, app quintet, J 3.8, C(10 )H),

J. Org. Chem. Vol. 75, No. 22, 2010 7753

JOC Article Davies et al.

4.15 (1H, dt, J 10.8, 3.8, C(6)H), 4.53 (2H, AB system, JAB 14.9, X-ray Crystal Structure Determination for 59. Data were collect-
NCH2Ph), 7.27-7.35 (5H, m, Ph); δC (100 MHz, CDCl3) 10.2 ed using an Enraf-Nonius κ-CCD diffractometer with graphite
(C(30 )), 21.2 (C(20 )), 24.9 (C(5)), 43.6 (C(4)), 52.5 (NCH2Ph), monochromated Mo KR radiation using standard procedures at
73.2 (C(10 )), 79.9 (C(6)), 127.7, 128.0, 128.7 (o,m,p-Ph), 136.5 150 K. The structure was solved by direct methods (SIR92); all
(i-Ph), 154.1 (CdO); m/z (ESI-) 248 ([M - H]-, 100%); HRMS non-hydrogen atoms were refined with anisotropic thermal
(ESI-) C14H18NO3- ([M - H]-) requires 248.1292; found parameters. Hydrogen atoms were added at idealized positions.
248.1291. The structure was refined using CRYSTALS.28
(RS,RS)-N(3)-Benzyl-5-(10 -hydroxybutyl)-1,3-oxazolidin-2-one X-ray crystal structure data for 61 [C14H19NO3]: M = 249.31,
58. Following general procedure 2, 56 (100 mg, 0.528 mmol) in monoclinic, space group P21/n, a = 12.0044(4) Å, b = 9.1663(4) Å,
CH2Cl2 (3.5 mL) was treated with Br3CCO2H (778 mg, 2.64 mmol) c = 12.0881(5) Å, β = 92.7130(18)°, V = 1328.63(9) Å3, Z = 4,
and m-CPBA (181 mg, 75%, 0.79 mmol), followed by DBU μ = 0.087 mm-1, colorless plate, crystal dimensions = 0.13 
(1.0 mL). Purification via flash column chromatography (gradient 0.18  0.21 mm3. A total of 3016 unique reflections were
elution, 50%f100% EtOAc in 30-40 °C petrol) gave 58 as a measured for 5 < θ < 27, and 3016 reflections were used in
colorless oil (117 mg, 89%, >99:1 dr): νmax (film) 3418 (O-H), 2957 the refinement. The final parameters were wR2 = 0.141 and
(C-H), 1726 (CdO); δH (400 MHz, CDCl3) 0.92 (3H, t, J 7.1, R1 = 0.065 [I > -3.0σ(I)].
C(40 )H3), 1.39-1.54 (4H, m, C(20 )H2, C(30 )H2), 3.30 (1H, app t, J Crystallographic data (excluding structure factors) have been
7.5, C(4)HA), 3.41 (1H, app t, J 7.5, C(4)HB), 3.53-3.56 (1H, m, deposited with the Cambridge Crystallographic Data Centre as
C(10 )H), 4.36 (1H, d, J 15.0, NCHAHBPh), 4.36-4.38 (1H, m, supplementary publication number CCDC 784949. Copies of
C(5)H), 4.49 (1H, d, J 15.0, NCHAHBPh), 7.26-7.38 (5H, m, Ph); the data can be obtained, free of charge, on application to CCDC,
δC (100 MHz, CDCl3) 13.8 (C(40 )), 18.7 (C(30 )), 34.5 (C(20 )), 45.7 12 Union Road, Cambridge, CB2 1EZ, UK [fax: þ44(0)-1223-
(C(4)), 48.3 (NCH2Ph), 72.1 (C(10 )), 75.7 (C(5)), 127.9, 128.0, 128.8 336033 or e-mail: deposit@ccdc.cam.ac.uk].
(o,m,p-Ph), 135.6 (i-Ph), 157.7 (C(2)); m/z (ESIþ) 250 ([M þ H]þ, (RS,SR)-1-N,N-Dibenzylamino-1-phenyl-2,3-epoxy-3-methyl-
100%); HRMS (ESIþ) C14H20NO3þ ([M þ H]þ) requires 250.1438; butane 73. Cl3CCO2H (1.20 g, 7.33 mmol) was added to a solution
found 250.1436. of 67 (500 mg, 1.47 mmol) in CH2Cl2 (10 mL) at rt, and the
X-ray Crystal Structure Determination for 58. Data were solution was stirred for 30 min. m-CPBA (1.08 g, 70%, 4.40
collected using an Enraf-Nonius κ-CCD diffractometer with mmol) was added, and the solution was stirred at rt for 1 h. The
graphite monochromated Mo KR radiation using standard proce- mixture was then diluted with CH2Cl2 (20 mL) and washed with
dures at 150 K. The structure was solved by direct methods (SIR92); satd aq Na2SO3 (50 mL portions) until starch-iodide paper
all non-hydrogen atoms were refined with anisotropic thermal indicated that no m-CPBA was present. The organic layer was
parameters. Hydrogen atoms were added at idealized positions. washed with satd aq NaHCO3 (4  50 mL), dried, and con-
The structure was refined using CRYSTALS.28 centrated in vacuo. Purification via flash column chromatogra-
X-ray crystal structure data for 58 [C14H19NO3]: M = 498.62, phy (gradient elution, 1%f5% Et2O in 30-40 °C petrol) gave
triclinic, space group P1, a = 9.6645(4) Å, b = 11.3513(4) Å, 73 as a colorless oil (516 mg, 98%, >99:1 dr): νmax (film) 3041
c = 12.7583(5) Å, R = 101.4022(16)°, β = 104.9826(16)°, γ = (C-H), 2961 (C-H), 1493; δH (400 MHz, CDCl3) 0.91 (3H, s,
90.623(2)°, V = 1322.54(9) Å3, Z = 4, μ = 0.088 mm-1, Me), 1.45 (3H, s, Me), 3.34 (1H, d, J 9.0, C(2)H), 3.65 (1H, d, J
colorless block, crystal dimensions = 0.12  0.16  0.24 mm3. 9.0, C(1)H), 3.80 (4H, AB system, JAB 13.5, N(CH2Ph)2), 7.14-
A total of 5982 unique reflections were measured for 5 < θ < 27, 7.49 (15H, m, Ph); δC (100 MHz, CDCl3) 18.8 (Me), 24.8 (Me),
and 2904 reflections were used in the refinement. The final param- 53.9 (N(CH2Ph)2), 56.2 (C(3)), 60.3 (C(1)), 63.2 (C(2)), 126.7,
eters were wR2 = 0.134 and R1 = 0.127 [I > 2.5σ(I)]. 127.2, 127.8, 128.1, 128.3, 129.0 (o,m,p-Ph), 139.9, 140.0 (i-Ph);
Crystallographic data (excluding structure factors) have been m/z (ESIþ) 358 ([M þ H]þ, 100%); HRMS (ESIþ) C25H28NOþ
deposited with the Cambridge Crystallographic Data Centre as ([M þ H]þ) requires 358.2165; found 358.2167.
supplementary publication number CCDC 784948. Copies of (RS,SR)-1-N,N-Dibenzylamino-1-isopropyl-2,3-epoxy-3-methyl-
the data can be obtained, free of charge, on application to CCDC, butane 74. Cl3CCO2H (265 mg, 1.63 mmol) was added to a solu-
12 Union Road, Cambridge, CB2 1EZ, UK [fax: þ44(0)-1223- tion of 68 (100 mg, 0.33 mmol) in CH2Cl2 (2 mL) at rt, and the
336033 or e-mail: deposit@ccdc.cam.ac.uk]. solution was stirred for 30 min. m-CPBA (120 mg, 70%, 0.48
(RS,RS)-N(3)-Benzyl-6-(10 -hydroxypropyl)-1,3-oxazinan-2-one mmol) was added, and the solution was stirred at rt for 21 h. The
59. Following general procedure 2, 57 (120 mg, 0.630 mmol) in mixture was then diluted with CH2Cl2 (10 mL) and washed with
CH2Cl2 (4.2 mL) was treated with Br3CCO2H (932 mg, 3.15 satd aq Na2SO3 (20 mL portions) until starch-iodide paper
mmol) and m-CPBA (216 mg, 75%, 0.95 mmol), followed by indicated that no m-CPBA was present. The organic layer was
DBU (1.0 mL). Purification via flash column chromatography washed with satd aq NaHCO3 (4  20 mL), dried, and concen-
(gradient elution, 50%f100% EtOAc in 30-40 °C petrol) gave trated in vacuo. Purification via flash column chromatography
59 as a colorless oil (132 mg, 84%, >99:1 dr): C14H19NO3 (gradient elution, 1%f5% Et2O in 30-40 °C petrol) gave 73 as
requires C, 67.45; H, 7.7; N, 5.6%; found C, 67.4; H, 7.6; N, a white solid (105 mg, 99%, >99:1 dr): mp 74-77 °C; νmax (film)
5.6%; νmax (film) 3390 (O-H), 3031 (C-H), 2934 (C-H), 1681 2958 (C-H), 2927 (C-H), 1493; δH (400 MHz, CDCl3) 0.78
(CdO); δH (400 MHz, CDCl3) 0.99 (3H, t, J 7.0, C(30 )H3), (3H, d, J 6.7, MeCHMe), 1.02 (3H, d, J 6.7, MeCHMe), 1.15
1.53-1.64 (2H, m, C(20 )H2), 1.87-1.91 (2H, m, C(5)H2), 3.17- (3H, s, C(3)Me), 1.36 (3H, s, C(3)Me), 1.80-1.89 (1H, m,
3.22 (1H, m, C(4)HA), 3.21-3.30 (1H, m, C(4)HB), 3.49-3.53 CHMe2), 2.11 (1H, app t, J 9.8, C(1)H), 2.92 (1H, d, J 9.8,
(1H, m, C(10 )H), 4.11-4.16 (1H, m, C(6)H), 4.54 (2H, AB C(2)H), 3.90 (4H, AB system, JAB 13.1, N(CH2Ph)2), 7.20-7.49
system, JAB 15.0, NCH2Ph), 7.26-7.35 (5H, m, Ph); δC (100 (10H, m, Ph); δC (100 MHz, CDCl3) 19.5 (Me), 19.8 (Me), 20.9
MHz, CDCl3) 9.9 (C(30 )), 23.8 (C(20 )), 25.5 (C(5)), 43.7 (C(4)), (Me), 24.5 (Me), 28.8 (CHMe2), 54.7 (N(CH2Ph)2), 56.6 (C(3)),
52.5 (NCH2Ph), 74.2 (C(10 )), 79.8 (C(6)), 127.6, 128.1, 128.7 60.8 (C(1)), 66.3 (C(2)), 126.6, 128.0, 129.2 (o,m,p-Ph), 140.6
(o,m,p-Ph), 136.5 (i-Ph), 153.8 (C(2)); m/z (ESI-) 248 ([M-H]-, (i-Ph); m/z (ESIþ) 346 ([M þ Na]þ, 100%); HRMS (ESIþ)
100%); HRMS (ESI-) C14H18NO3- ([M-H]-) requires 248.1292; C22H30NOþ ([M þ H]þ) requires 324.2322; found 324.2325.
found 248.1292. X-ray Crystal Structure Determination for 74. Data were
collected using an Enraf-Nonius κ-CCD diffractometer with
(28) Betteridge, P. W.; Carruthers, J. R.; Cooper, R. I.; Prout, C. K.;
graphite monochromated Mo KR radiation using standard
Watkin, D. J. CRYSTALS; Chemical Crystallography Laboratory, Uni- procedures at 150 K. The structure was solved by direct
versity of Oxford: U.K., 2010; Issue 14. methods (SIR92); all non-hydrogen atoms were refined with

7754 J. Org. Chem. Vol. 75, No. 22, 2010

Davies et al.
JOC Article
anisotropic thermal parameters. Hydrogen atoms were (10 mL) and washed with satd aq NaHCO3 (10 mL) and brine
added at idealized positions. The structure was refined using (10 mL). The organic layer was dried and concentrated in
CRYSTALS.28 vacuo. Purification via flash column chromatography (eluent
X-ray crystal structure data for 74 [C22H29NO]: M = 323.48, 40-60 °C petrol/EtOAc, 5:1) gave 77 as a white solid (72 mg,
monoclinic, space group P21/c, a = 12.1182(2) Å, b = 62%, >99:1 dr): mp 90-94 °C; νmax (film) 3315 (O-H), 2971
10.2863(2) Å, c = 15.4746(3) Å, β = 97.3039(8)°, V = (C-H); δH (400 MHz, CDCl3) 0.64 (3H, s, C(3)MeA), 0.98
1913.28(6) Å3, Z = 4, μ = 0.068 mm-1, colorless plate, crystal (3H, s, C(3)MeB), 2.99-3.02 (2H, m, N(CHAHBPh)2), 3.84
dimensions = 0.18  0.21  0.28 mm3. A total of 4354 unique (1H, d, J 9.4, C(1)H), 3.87-3.91 (2H, m, N(CHAHBPh)2), 4.07
reflections were measured for 5 < θ < 27, and 2864 reflections (1H, J 9.4, C(2)H), 7.25-7.47 (15H, m, Ph); δC (100 MHz,
were used in the refinement. The final parameters were wR2 = CDCl3) 24.7 (Me), 27.9 (Me), 52.9 (N(CH2Ph)2), 53.6 (N(CH2Ph)2),
0.090 and R1 = 0.043 [I > -3.0σ(I)]. 60.0 (C(1)), 73.3 (C(2)), 127.2, 127.5, 128.0, 128.3, 128.6, 130.3
Crystallographic data (excluding structure factors) have been (o,m,p-Ph), 138.2, 139.8 (i-Ph); m/z (ESIþ) 376 ([M þ H]þ,
deposited with the Cambridge Crystallographic Data Centre as 100%); HRMS (ESIþ) C25H30NO2þ ([M þ H]þ) requires
supplementary publication number CCDC 784950. Copies of 376.2271; found 376.2270.
the data can be obtained, free of charge, on application to CCDC, Method B. K2CO3 (127 mg, 0.92 mmol) was added to a solu-
12 Union Road, Cambridge, CB2 1EZ, UK [fax: þ44(0)-1223- tion of 76 (37 mg, 0.09 mmol) in MeOH (2.0 mL). The mixture
336033 or e-mail: deposit@ccdc.cam.ac.uk]. was heated to 60 °C for 16 h and then concentrated in vacuo. The
(RS,SR)-4,4-Dimethyl-5-[(N,N-dibenzylamino)(phenyl)methyl]- residue was dissolved in CH2Cl2 (10 mL) and washed with satd
1,3-dioxolan-2-one 76. Following general procedure 2, 67 (170 mg, aq NaHCO3 (10 mL) and brine (10 mL). The organic layer was
0.500 mmol) in CH2Cl2 (3.3 mL) was treated with Br3CCO2H dried and concentrated in vacuo. Purification via flash column
(1.48 g, 5.00 mmol) and m-CPBA (184 mg, 70%, 0.75 mmol), chromatography (eluent 40-60 °C petrol/EtOAc, 5:1) gave 77
followed by DBU (1.0 mL). Purification via flash column chroma- as a white solid (34 mg, 98%, >99:1 dr).
tography (eluent 40-60 °C petrol/EtOAc, 5:1) gave 43 as a white X-ray Crystal Structure Determination for 77. Data were
solid (180 mg, 90%, >99:1 dr): mp 126-128 °C; νmax (KBr) collected using an Enraf-Nonius κ-CCD diffractometer with
2981 (C-H), 1797 (CdO); δH (400 MHz, CDCl3) 0.97 (3H, s, graphite monochromated Mo KR radiation using standard
C(5)MeA), 1.13 (3H, s, C(5)MeB), 3.19 (2H, d, J 13.7, N- procedures at 150 K. The structure was solved by direct
(CHAHBPh)2), 3.99 (2H, d, J 13.7, N(CHAHBPh)2), 4.07 (1H, methods (SIR92); all non-hydrogen atoms were refined with
d, J 11.1, C(10 )H), 5.11 (1H, d, J 11.1, C(5)H), 7.10-7.49 (15H, anisotropic thermal parameters. Hydrogen atoms were
m, Ph); δC (100 MHz, CDCl3) 21.4 (Me), 26.8 (Me), 53.5 added at idealized positions. The structure was refined using
(N(CH2Ph)2), 60.2 (C(10 )), 84.1 (C(4)), 84.2 (C(5)), 127.2, 127.5, CRYSTALS.28
128.4, 128.8, 129.3, 130.3 (o,m,p-Ph), 138.1, 139.0 (i-Ph), 153.9 X-ray crystal structure data for 77 [C25H29NO2]: M = 375.51,
(C(2)); m/z (ESIþ) 424 ([M þ Na]þ, 70%); HRMS (ESIþ) monoclinic, space group P21/c, a = 10.14550(10) Å, b =
C26H28NO3þ ([M þ H]þ) requires 402.2064; found 402.2067. 8.47320(10) Å, c = 24.9311(4) Å, β = 97.0646(6)°, V =
X-ray Crystal Structure Determination for 76. Data were 2126.93(5) Å3, Z = 4, μ = 0.073 mm-1, colorless block, crystal
collected using an Enraf-Nonius κ-CCD diffractometer with graphite dimensions = 0.20  0.20  0.20 mm3. A total of 4820 unique
monochromated Mo KR radiation using standard procedures at reflections were measured for 5 < θ < 27, and 2564 reflections
150 K. The structure was solved by direct methods (SIR92); all were used in the refinement. The final parameters were wR2 =
non-hydrogen atoms were refined with anisotropic thermal 0.046 and R1 = 0.040 [I > 3.0σ(I)].
parameters. Hydrogen atoms were added at idealized positions. Crystallographic data (excluding structure factors) have
The structure was refined using CRYSTALS.28 been deposited with the Cambridge Crystallographic Data
X-ray crystal structure data for 76 [C26H27NO3]: M = 401.51, Centre as supplementary publication number CCDC 784952.
triclinic, space group P1, a = 8.7549(2) Å, b = 9.8380(3) Å, Copies of the data can be obtained, free of charge, on
c = 14.0722(5) Å, R = 85.2408(11)°, β = 83.4949(12)°, γ = application to CCDC, 12 Union Road, Cambridge, CB2
66.4693(13)°, V = 1103.16(6) Å3, Z = 2, μ = 0.078 mm-1, 1EZ, UK [fax: þ44(0)-1223-336033 or e-mail: deposit@ccdc.
colorless block, crystal dimensions = 0.21  0.24  0.27 mm3. A cam.ac.uk].
total of 4962 unique reflections were measured for 5 < θ < 27, (4RS,5SR,10 SR)-4-[(N,N-Dibenzylamino)(phenyl)methyl]-5-
and 4962 reflections were used in the refinement. The final methyl-1,3-dioxolan-2-one 82. Br3CCO2H (2.96 g, 10.0 mmol)
parameters were wR2 = 0.100 and R1 = 0.063 [I > -3.0σ(I)]. was added to a stirred solution of 78 (265 mg, 1.00 mmol) in
Crystallographic data (excluding structure factors) have CH2Cl2 (6.6 mL), and the resultant mixture was stirred at rt for
been deposited with the Cambridge Crystallographic Data 10 min. m-CPBA (367 mg, 70%, 1.50 mmol) was added in one
Centre as supplementary publication number CCDC 784951. portion, and the reaction mixture was stirred at rt for 3 days.
Copies of the data can be obtained, free of charge, on DBU was added at 0 °C, and the resultant mixture was stirred at
application to CCDC, 12 Union Road, Cambridge, CB2 rt for 2 h. Satd aq NaHCO3 (10 mL) was added, and the layers
1EZ, UK [fax: þ44(0)-1223-336033 or e-mail: deposit@ccdc. were separated. The organic layer was washed with satd aq
cam.ac.uk]. NaHCO3 (2  10 mL) and brine (10 mL) and then dried and
(RS,SR)-1-N,N-Dibenzylamino-1-phenyl-3-methyl-butane-2, concentrated in vacuo to give an 85:15 mixture of 82 and 83 as a
3-diol 77. Method A. Cl3CCO2H (253 mg, 1.55 mmol) was added colorless oil (298 mg, 77%, 82:83, 85:15). An analytical sample
to 67 (106 mg, 0.310 mmol) in CH2Cl2 (2 mL) at rt, and the of 82 (>95:5 dr) was obtained after exhaustive flash column
resultant solution was stirred for 30 min. m-CPBA (80 mg, 73%, chromatography: νmax (film) 2986 (C-H), 1803 (CdO); δH (400
0.34 mmol) was added, and the reaction mixture was stirred at MHz, CDCl3) 0.94 (3H, d, J 9.3, C(5)Me), 3.29 (2H, d, J 13.5,
40 °C for 21 h. The mixture was then cooled to rt, diluted with N(CHAHBPh)2), 3.95 (2H, d, J 13.5, N(CHAHBPh)2), 4.07 (1H,
CH2Cl2 (10 mL), and washed with satd aq Na2SO3 (10 mL app d, J 9.3, C(10 )H), 5.11 (1H, q, J 9.3, C(5)H), 5.43-5.55 (1H,
portions) until starch-iodide paper indicated that no m-CPBA m, C(4)H), 7.10-7.49 (15H, m, Ph); δC (100 MHz, CDCl3) 14.5
was present. The organic layer was washed with satd aq (Me), 53.6 (N(CH2Ph)2), 59.3 (C(10 )), 75.6 (C(5)), 77.7 (C(4)),
NaHCO3 (4  10 mL), dried, and concentrated in vacuo. The resi- 127.1, 128.4, 128.5, 128.8, 128.9, 133.5 (o,m,p-Ph), 138.9, 139.0
due was dissolved in MeOH (4.0 mL); K2CO3 (428 mg, 3.1 mmol) (i-Ph), 154.6 (C(2)); m/z (ESIþ) 388 ([M þ H]þ, 100%); HRMS
was added; and the mixture was stirred at rt for 16 h and then (ESIþ) C25H26NO3þ ([M þ H]þ) requires 388.1907; found
concentrated in vacuo. The residue was dissolved in CH2Cl2 388.1904.

J. Org. Chem. Vol. 75, No. 22, 2010 7755

JOC Article Davies et al.

Acknowledgment. The authors would like to thank Aji- Supporting Information Available: Full details of all
nomoto Co., Inc. for funding (W.K.), the Oxford Chemical experimental procedures, characterization data, copies of
1
Crystallography Service for the use of their X-ray diffrac- H and 13C NMR spectra, and crystallographic information
tometers, Helen R. Storr for assistance with NMR experi- files (for structures CCDC 784948-784952). This material
ments, and Michael C. Willis and Robert H. Snell for is available free of charge via the Internet at http://pubs.
assistance with Chiral HPLC analysis. acs.org.

7756 J. Org. Chem. Vol. 75, No. 22, 2010