7474 J. Org. Chem.

1993,58, 7474-7481

Charge-Directed Conjugate Addition Reactions of Silylated

a-&Unsaturated Amidate Anions
Manning P. Cooke, Jr.' and Charles M. PollocktJ
Department of Chemistry, Washington State University, Pullman, Washington 99164
Received July 20, 19930

A variety of N-substituted a-silylated-a,@-unsaturatedamidate anions (2) have been found to be

excellent Michael acceptors in charge-directed conjugate addition reactions with Grignard and
organolithium reagents. The effects of olefin substitution, Si-substitution,N-substitution,and amidate
counterion have been studied. Anionic acceptors may be prepared in situ by the addition of silylated
vinyllithium reagents to isocyanates and then allowed to undergo conjugate addition reactions with
subsequently added nucleophiles, but it was found to be more efficient to isolate neutral acceptors
and regenerate the acceptor anion through the use of excess nucleophile. @-Substitutedacceptors
were found to react only with reactive organolithium reagents while a @,B-disubstitutedacceptor
failed to undergo conjugate addition reactions. A primary amide acceptor (14d) also undergoes
addition reactions with larger quantitites of nucleophilessuggestingthat dianionicamidate acceptors
(31) are involved. Diene acceptor 24 was found to undergo a 1,6-addition reaction with n-BuLi.
Sodium and potassium amidate salts were found to be inferior to lithium and magnesium salts in
addition reactions in keeping with the expectation that an increase in carbonyl-groupcharge burden
retards conjugate reactions. Triphenylsilyl-containing acceptor 16 was found to be more reactive
in reactions with n-BuMgC1 but less reactive with bulkier tert-BuMgC1. Adduct dianions can be
monoalkylated with alkyl iodides and used in Peterson olefination reactions.

Introduction jugate addition pathway to predominate.6 Others have

The addition of stabilized nucleophiles to carbonyl- found that anions derived from certain secondary amides
activated olefins constitutes an important class of carbon- undergo such charge-directedconjugateaddition reactions
carbon bond forming reactions.2 In general, reactive with some organolithiumreagents.' In our study of charge-
nucelophiles such as Grignard and alkyllithium reagents directed conjugate addition reactions of unsaturated
undergo carbonyl 1,2-addition reactions with a,@-unsat- carboxylate salts, we found that a-silylated-a,@-unsatur-
urated carbonyl derivatives rather than Michael or con- ated carboxylate salts are excellent acceptors in reactions
jugate addition reactions with the polarized olefinic unit. with Grignard and organolithium reagents.6h The ben-
While reactions of strong nucleophiles with tertiary a,@- eficial effects of the a-silyl group presumably arise from
unsaturated amides likewise usually give products arising the additional stabilization of the anions formed in the
from carbonyl addition: there are scattered exceptions.4vs addition reactions as well as from suppression of polym-
We have previously shown that the placement of a unit erization reactions.* These results suggested that a-si-
of negative charge adjacent to the carbonyl group in a,@- lylated-a,@-unsaturatedamidate anions (2) also might be
unsaturated carbonyl derivatives suppresses the 1,2- excellent acceptors in charge-directed conjugate addition
nucleophilic addition pathway thereby allowing the con- reactionsgiving,after hydrolyticdeailylation,@-substituted
amides and thus a more general solution to the problem
t Present address: Union Camp, Chemical Producta Division, West of 1,4-vs 1,Badditionin unsaturated amides. Futhermore,
Lathrop Ave., Savannah, GA 31402. the required anionic acceptors (2) should be directly
0 Abstract publiihed in Advance ACS Abstractrr, November 15,1993.
(1) Taken in part from the Ph.D. Thesis of C. M. Pollock, Washington available from the addition of nucleophilic a-silylvinyl
State University, Pullman, WA, 1989. reagents (1) to isocyanates9enabling the overall reaction
(2) (a) Bergman, E. D.; Ginsburg, D.; Pappo, R. Org. React. (N.Y.)
1969,10, 179. (b) House, H. 0. Modern Synthetic Reactions, 2nd ed.; sequence shown in Scheme I. We anticipated that
Benjamin: Menlo Park, 1972; p 535. (c) Stowell, J. C. Carbanions in intermediate dianion 3 either could be protonated directly
Organic Synthesls; Wiley-Interscience: New York, 1979. (d) Patai, S., and then desilyated to give @-substitutedamides 4 (E =
Rappoport, Z. In The Chemistry ofdlkenes; Patai, S., Ed.; Interscience:
London, 1W Vol. 1, p 469. (e) Bureon, H. A. Org. React. 1949,6,79. (e) H)or could be further elaborated at C, by treatment with
Perlmuttar, P. Conjugate Addition Reactions in Organic Synthesis;
Pergamon Press: New York, 1992. (fj Jung, M. E. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Us.;Pergamon Press: New (6) (a) Cooke, M. P., Jr.; Goswami, R. J. Am. Chem. SOC.1977,99,642.
York, 1991; Chapt. 1.1. (g) Lee,V. J. Zbid. Chapta. 1.2,1.3. (h) Schmalz, (b) Cooke, M. P., Jr. Tetrahedron Lett. 1979,2199. (c) Cooke, M. P., Jr.;
H.-G. Zbid. Chapt. 1.5 (i) Hulce, M.; Chapdelaine, M. J. Zbid. Chapt. 1.6. Burman, D. L. J. Org. Chem. 1982,47,4956. (d) Cooke, M. P., Jr. Zbid.
(3) (a) Maxim, N.; Ioanid, N. Bull. SOC.Chim. Roumania 1928, 10, 1982,47,4963. (e) Cooke, M. P., Jr. Zbid. 1983,48,744. (fj Cooke, M. P.,
2 H 8 . (b) Klein, J. Tetrahedron 1964,20, 465. Jr.; Jaw, J-Y. Zbid. 1986,51, 768. (g) Cooke, M. P., Jr.; Widener, R. K.
(4) (a) Kharasch, M. S.; Reinmuth, 0. Grignard Reactions of Non- Zbid. 1987,52,1381. (h) Cooke, M. P., Jr. Zbid. 1987,52,5729. (i) Cooke,
metallic Substances, Prentice-Hall: New York, 1954; pp 875-876, 885. M. P., Jr.; Jaw, J.-Y. Synth. Commun.1992,22,2213. (j) Cooke, M. P.,
(b)Mpango,G.B.;Mahalanabis,K.K.;Mahdavi-Damghani,Z.;Snieckus,Jr.; Jaw, J.-Y. J. Org. Chem. 1993,58, 267.
V. Tetrahedron Lett. 1980,21,4823. (7) (a) Mpango, G. B.; Snieckus, V. Tetrahedron Lett. 1980,4827. (b)
(5) (a) Alexakis, A. J.; Berlan, A.; Besace, Y. Tetrahedron Lett. 1986, Baldwin, J. E.; Dupont, W. A. Tetrahedron Lett. 1980, 21, 1881. (c)
27, 1047. (b) Nagashima, H.; Ozeki, N.; Washiyama, M.; Itoh, K. Tamaru, Y.; Kagotani, M.; Furukawa, Y.; Amino, Y.; Yoshida, Z.
Tetrahedron Lett. 1986, 26, 657. (c) Soai, K.; Ookawa, A.; Nohara, Y. Tetrahedron Lett. 1981,22, 3413.
Synth. Commun. 1983, 13, 27. (d) Mukaiyama, T.; Iwasaw, N. Chem. (8) (a) Boeckman, R. K. Tetrahedron 1983,39,925; Boeckman, R. K.
Lett. 1981, 913. (e) Soai, K.; Machida, H.; Ookawa, A. J. Chem. SOC. J. Am. Chem. SOC.1974,96,6179. (b) Stork, G.; Singh, J. Zbid. 1974,96,
Chem. Commun. 1986, 469. (0Tomioka, K.; Suenaga, T.; Koga, K. 6181. (c) Stork, G.; Ganem, B. Zbid. 1973,95,6152.
Tetrahedron Lett. 1986,27,369. (g) Vandewalle, M.; Vander Eycken, J.; (9) Wakefield, B. J. The Chemistry of Organolithium Compounds;
Oppolzer, W.; Vullioud, C. Tetrahedron 1986,42,4035. Pergamon: New York, 1974, p 128.
QQ22-3263/93/1958-7474$04.00/0 0 1993 American Chemical Society
Charge-Directed Conjugate Addition Reactions J. Org. Chem., Vol. 58, No.26, 1993 7476
Scheme I Scheme I1
0 0

SiR,

1 2
11 12

to execute owing to difficulties encountered in the intro-

duction of exact quantities of organometallic reagents and
typically reactions gave mixtures (eq 2). It proved most
SiU3 E
1. 5,-78%
3 4
PhNCO
2. n-BuMgCI,20'C
3. NaOH
* '- CONHPh + 9aor 10b (2)

electrophiles prior to desilylation giving 4, E # H. We 10a (R = ~ B u (50%)

)
now report the results of our exploration of this scheme. b ( R = Et)

Results and Discussion efficient to execute Scheme I in two steps: the preparation
of protonated acceptors (2-H) by the addition of 1 to
In order to test the feasibility of this scheme, several isocyanates followed by regeneration of acceptor anions
isocyanates were treated with excess trimethylsilyl vinyl 2 and subsequent conjugate addition to the anionic
magnesium bromide (5) as shown in eq 1. The addition acceptor using the nucleophilic organometallic reagent as
both the base and nucleophile. To this end, a variety of
a-silylated-a,&unsaturatedamides were prepared and the
conjugate addition reactions of their amidate anions were
studied. The effects of N-substitution, &substitution, Si-
substitution, and amide counterion on conjugate addition
1 SiMe3 1 reactions were investigated.
Synthesis of Silylated Amides. Silylated amide ion
6a ( R = Ph) precursors 12 in general were readily prepared by the
b (R = Bfl)
c (R = Me) addition of organolithium reagents to isocyanates at -78
0 "C followed by a protonation of the product amidateanions
(Scheme11,Table I). The required organolithiumreagents
were in turn prepared from corresponding vinyl iodides
11 by lithium-iodine exchange reactions with either
Me3Si SiMe3 Me3& &Me,
n-BuLi or tert-BuLi. Previously, unreported iodide 19
8a (92%)
was prepared by the hydroalumination-iodination se-
7
b (71%) quence shown in eq 3 which was patterned after the known
C (73%)
0

H O or F NHR (1)
____t

19
Me3Si

9a (97%) procedure for the preparation of 17.1' Lithium-iodine

b (77%) exchange under conditions known to give retention of
c (91%) configuration11J2followed by protonation afforded (2)-
of phenyl isocyanate, benzyl isocyanate, or methyl iso- 1-(triphenylsily1)-1-hexenewhose configuration followed
cyanate to a 4-fold excess of 6 in THF at -78 "C followed from its lH NMR olefinic coupling constant (J = 14 Hz).'~
by reaction at 20 OC for 2 h gave silylated amides 8 in good Iodo diene 23 was prepared as shown in eq 4. In this case
yields. Removal of the a-trimethylsilyl group was readily
accomplishedby either brief heating with NaOH-MeOH-
H20 or by treatment with nBuaNF.1° While the formation
of acceptor amidate anions 6 occurs rapidly at -78 OC, the
* 27
SiMe3 2,
1. DIBAL, Et20
*

conjugate addition reactions require higher temperatures

(vide infra).
In principle, the execution of Scheme I should be
achievable in a onspot operation in which the nucleophilic
vinylsilane 1is allowed to react with an isocyanate at low
temperature followed by the introduction of the appro- 20
priate Grignard or organolithium reagent which would
then undergo the desired conjugate addition reaction at the hydroalumination-iodination sequence initially gave
a higher temperature. In practice this proved to be tedious 28 @I2= 9551,but this compound rapidly isomerized in
sunlight to the 2-isomer23 (>985% 2).The single primary
(10) Woodbury, R.P.;Rathke, M.W.J. Org. Chem. 1978,43,881. amide 14d was prepared by the addition of 1-(trimeth-
7476 J. Org. Chem., Vol. 58, No. 26, 1993 Cooke and Pollock
Table I. Silylated Unsaturated Amides (ea 3) temperatures in the presence of alkali generallygave good
halide RLi RNCO amide % yield yields of the a-silylatedadducts 29, althoughin many cases,
- as noted in Table 11,adducts were directly desilylated to
-a - PhNCO 83
Y O M R give 30 by briefly heating alkaline (NaOH) solutions of 29
SiMq SiMe3 in MeOH-H20.
In general, efficient addition reactions of Grignard and
13* 14 (R = Ph) alkyllithium reagents to amidate acceptors occurred in all
13 a BnNCO 14b (R = Bn) 78 cases except the one derived from 8,B-disubstituted
13 a MeNCO 14c (R = Me) 63 acceptor 26. Such highly substituted acceptors are often
tert-BuLi MesSiNCO 14d (R = H) 79 found to be resistant to Michael addition reactions16except
Br tert-BuLi PhNCO 66 in cases involvingintramolecularaddition reactiomeThe
sw3 siFll3 rate of addition of alkyllithium reagents to deprotonated
acceptors 2 was found to be much faster than the reaction
1s c 16
of the corresponding Grignard reagentto the same acceptor
n-BuLi PhNCO Buy
coNHPh 76
(entries3,7, and 8). The less-reactive nucleophiles 2-lithio-
1,3-dithiane (entry 12) and n-BuzCu(CN)Liz (entry 11)
SiMq SiMq also undergo reactions with 14a, but the enolate of tert-
butyl acetate (entry 13) was unreactive.
17d 18 It is interesting to note that the a-silyl group in 14a
n-BuLi PhNCO 69 does indeed render ita amidate anion more reactivetoward
conjugate addition reactions than its unsilylated analog
Siphg sw3 (N-phenyl acrylamide).'b The latter acceptor was found
to react only poorly with PhLi and MeLi and not at all
19 20 with PhMgBr and MeaCuLi, while excellent results were
Ph n-BuLi PhNCO Ph 64 obtained with 14a in these cases (entries 10, 2, and 11).

SiMq
b...-SMe3
It is also noteworthy that even unsubstituted amide
14d undergoes conjugate addition reactions (entries 22-
25); however, yields were lower under standard conditions
employing 3 equiv of nucleophile(oneof which is normally
used to generate the amidate anion). Yields improved
n-BuLi PhNCO 79
progressively when larger amounts of nucleophile were
used (entries 23 and 261, suggesting that additional RM
SiMq siMc3 may be consumed in the formation of a dimetalated amide
dianion 31 which may also undergo addition reactions
23 24
giving trianions 32 (eq 5). Analogous di- and trianions
P tert-BuLi PhNCO Ft 49 0 0
Bu+ I Bu+coMPh
Siq siMc3
SiMe3 SiMe,
28, 26
31 32
*
a Grignard reagent 5 used. Reference 24. Reference 25. Ref-
(5)
erence 11. Reference 6h.f Reference 26.
Scheme I11 have been reported in reactions of phenylacetamide with
RN
n-BuLi.ls
In the cases involving 8-substituted acceptors (entries
RNM ).
1. RNM CONHR' 29-33), conjugate addition reactions were observed with
12 2-
2. H* Ri alkyllithium reagents (entries 29,31, and 331, but not with
3. NaOH i Grignard reagents (entries 30 and 32). In the case of the
diene acceptor derived from 24, only 1,6-addition was
29 (X = R3Si) observed in its reaction with n-BuLi (entry 33). Proto-
30 (X = H) nation of the initial adduct gave an unresolved mixture of
isomeric @,y-unsaturatedamides which, upon hydroge-
ylsily1)vinyllithium to trimethylsilyl isocyanate followed nation and desilylation afforded N-phenylnonanamide in
by hydrolytic removal of the N-TMS group.l4 good yield. Similar 1,6-addition has been observed with
Conjugate Addition Reactions. The conjugate ad-
dition reactions of a number of strong nucleophiles with (11) Zweifel, G.;Le*, W. J. Org. Chem. 1978,#, 2739.
amidate anions derived from silylatedunsaturated amides (12) (a) Cunico, R. F. J. Organomet. Chem. 1973,60,219. (b)Brook,
A. G.;Duff,J. M.; Reynolds, W. F. Zbid. 1976,121, 293. (c) Zweifel, 0.;
12 were investigated (Scheme 111)and results are shown Murray, R. E.; On, H. P. J. Org. Chem. 1981,46,1292. (d) N e ,E.;
in Table 11. In general, amides were added in THF to a Takahaehi, T. J. Am. Chem. SOC.1986,108,3402.
3-fold excess of the organometallicreagent at -78 OC,and (13) Brook, A. G.;Duff,J. M.; Reynolds, W. F. J. Organoket. Chem.
1976,121,293.
then the mixture was kept at room temperature for 4 h (14) Parker, K. A.; Gibbons,E.G. Tetrahedron Lett. 1975,981.
prior to a protic quench (method A). It should be noted, (16) March, J. Advanced Organic Chemistry: Reactions, Mechanisms
and Structure; 2nd ed.;McGraw-Hill: New York, 1977; p 729.
however, that in the cases examined, inverse additions (16) Kaiser,E. M.;Vaux, R. L; Hauser, C. R. J. Org. Chem. 1967,32,
gave similar results. Workups which avoided elevated 3640.
Charge-Directed Conjugate Addition Reactions J. Org. Chem., Vol. 58, No. 26, 1993 7477
Table 11. Conjugate Addition Reactions of Unsaturated Amidate Anions
silylated deailylated*
entry acceptor RM method0 (% yield) R1 RN R' (% yield)
1 14a MeMgBr A 29a (89) H Me Ph 30a(92)
2 PhMgBr A 29b (83) Ph 30b (94)
3 c-Ca&fgBr A 29c (88) c-crlHH8 30c (71)
4 CHdHMgBr A 29d (91) CHdH 30d (73)
5 CH4HCHZMgCl A CHdHCHz 30e (92)
6 n-BuMgC1 A n-Bu 30f (99,709
7 t-BuMgCl B t-Bu 3Og (52)
8 n-BuLi A n-Bu 30f (87)
9 t-BuLi A t-Bu 3W (83)
10 PhLi A 29b (78) Ph 30b (83)
11 n-BuguCNLiz A n-Bu 301 (95)
12 2-lithio-1,3-dithiane A 2-dithianyl 30h (97)
13 LiCHzCOOBut C (0) CH2COOBut (0)
14 14b PhMgBr A H Ph Bn 30i (91)
15 n-BuMgC1 A Bu 30j (84)
16 14c PhMgBr A 29k (78) Ph Me 30k(61)
17 n-BuMgC1 A n-Bu 301 (71)
18 c-CsH&fgBr A c-C~H~ 30m (68)
19 t-BuMgC1 D t-Bu 3011 (68)
20 PhLi A Ph 30k (74)
21 n-BuLi A n-Bu 301 (74)
22 lad n-BuMgC1 A n-Bu H 3 0 (30)
~
23 PhMgBr E Ph 30q (69)
24 n-BuLi A n-Bu 3 0 (58)
~
25 PhLi E Ph 30q (62, 34d,53.)
26 16 n-BuLi A n-Bu Ph 30ff(88)
27 n-BuMgC1 A n-Bu 30ff (85)
28 PhMgBr A Ph 30W (80)
29 18 n-BuLi A n-Bu n-Bu 30t (93)
30 n-BuMgC1 A n-Bu 3ot (0)
31 22 n-BuLi A Ph n-Bu 30u (52)
32 n-BuMgC1 A 30u (0)
33 24 n-BuLi A H n-hexyl (72)r
34 26 n-BuLi A (0)
Method A acceptor 12 added to 3 equiv of RM at -78 OC and then 20 "C, 4 h; B as in A but 5 equiv RM and then 20 "C, 20 h; C acceptor
deprotonated with 1equiv of n-BuLi followed by 1.1equiv RM and then 0 "C, 4 h; D as in B but 50 h; E as in A but 4.5 equiv of RM.* 29
directly desilylated with NaOH-HzO-MeOH, brief reflux. Inverse addition of RM to acceptor. T w o equivalents of RM. e Equivalents of
RM. f X = SiPb. 8 Hydrogenated (Hz, PtOz) to N-phenylnonanamide.

cuprates and N,I?-diethy1-2,4-hexadienamidel7 and with It should be added, however, that this interpretation is
alkyllithium reagents and an analogous a-silylated 1,3- quite simplistic insomuch as no information is available
butadienyl borane acceptor.'* Grignard reagents appeared on aggregate structure or metal-metal exchange.
to polymerize 24. The effect of substitution on silicon was also examined
The effects of the amidate counterion on the ease of throughacceptors 14a, 16, and 20. The latter two acceptors
conjugate addition reactions were also briefly investigated. containing the more electron-withdrawing triphenylsilyl
The potassium and sodium amidate salts of 14a (2, R = group might be expected to be better Michael acceptors
Ph, R1= H, R1 = Me, M = K+or Na+)were prepared from owing to an increase in adduct anion stability. However,
14a and KH and NaH or NaN(SiMe& respectively. Both &substituted acceptor 20, like ita trimethylsilyl counter-
the sodium and potassium salts underwent addition part 18, also failed to undergo addition reactions with
reactions with excess n-BuMgC1under standard conditions Grignard reagents. In a competition experiment in which
(4 h, 20 "C) giving, after desilylation, 30f in 83 and 75% separate but equal amounts of 14a and 16 were treated
yields, respectively. It is interesting to note that the with 1.9 equivalents of n-BuMgC1 (-30 OC, 1h), adduct
sodium salt of 14a is apparently a better Michael acceptor 30f was obtained in 41 and 58% yield,2O respectively,
than the corresponding carbonylate salt which does not suggesting that triphenylsilyl-containngacceptor 16 is a
undergo addition reactionswith Grignard When slightly better acceptor. However,in a similar experiment
the chloromagnesium,sodium,and potassium salts of 14a with equivalent amounts of 14a and 16 and 5 equiv of
were treated with 0.9 equiv of n-BuMgC1under identical tert-BuMgCl(20 h at 20 OC) adduct 30g was produced in
conditions (-15 "C, 1h), 30f was obtained in 53,37, and 52 and 39% yields, respectively. In this case, the tri-
29 % yields, respectively.lQThese data are in keeping with methylsilylated acceptor (14a) actually underwent the
the expectation that amidates with less covalently bound addition reaction at a faster rate with this nucleophile,
counterions have a greater charge burden associated with and it is likely that the larger size of the triphenylsilyl
the carbonyl unit and hence undergo conjugate addition group in 16 retards the reaction rate with bulky tert-
reactions to give electron-rich "dianions" less readily.6hTi BuMgC1.
Dianion Alkylation. The dianions (3, R1 = H, R1 =
(17) Daviaud, G.;Miginiac, P. Tetrahedron Lett. 1973, 3345. Me, R = Ph) generated upon the addition of Grignard or
(18) Cooke, M. P., Jr.; Widener, R. K. J. Am. Chem. SOC.1987,109, alkyllithium reagents to 14a could be satisfactorily alky-
931.
(19)The other product isolated in all cases was N-phenyl-3-methox-
ypropnnamide,the product of MeOH additionto unreaded acceptor 148 (20) Additionally, N-phenyl3-methoxypropanamidewas isolated in
followed by desilylation. 45% from 14e and in 32% from 16.'9
 7478 J. Org. Chem., Vol. 58,No. 26,1993 Cooke and Pollock

Scheme IV and PhMgBr in diethyl ether, and allylmagnesiumchloride, and

RE vinylmagnesium bromide in tetrahydrofuran (THF) were ob-
1. RM CONHPh tained from Aldrich Chemical Co. Reactions involving organo-
14a ____c
RN
metallic reagents were conducted under an argon atmosphere.
2. E+ Reactions conducted at -78 "C employed a dry ice-acetone bath.
(3. NaOH) X THF and diethyl ether were distilled from sodium benzophenone
ketyl. Column chromatography was conducted with Baker 60-
33 X Me&) 200 mesh silica powder as described by Still et al." Preparative
34 {XZH)
thin-layer chromatography (PTLC) employed Merck 60 P F a
lated by alkyl iodides as shown in Scheme IV and Table silica gel. 1HNMR spectra (90MHz) and 13CNMR spectra (22.5
111. Reactions of lithium salts (entries 1-5) were notably MHz) were recorded on CDCl3solutions with TMS as an internal
faster than those of chloromagnesium salts (entries 6, 7) standard. Melting points and boiling points are uncorrected.
and the lat,tercould only be alkylated with MeI. T h e use Boiling points for bulb-to-bulb distillations refer to air bath
temperatures. Analyses were performed by Galbraith Labora-
of benzyl chloride or benzyl bromide with chloromagne- tories, Knoxville, TN.
sium salts resulted in the formation of complex mixtures N-Phenyl-2,4-bis(trimethylsilyl)-4-pentenamide (8a). To
containing significant amounts of protonated adducts 33 a 0.6 M solution of 1-(trimethylsily1)vinylmagnesium bromideB
(RE = H).In the alkylation of the lithium adduct in entry (5) (9.2 mL, 5.5 mmol) in THF at -78 "C was added freshly
3, the longer reaction time required with n-BuI as the distilled phenyl isocyanate (0.14mL, 1.3 mmol). The reaction
alkylating agent resulted in some 0-alkylationzl of the mixture was warmed to 20 "C and stirred for 2 h, whereupon it
amidate monoanion as well (eq 6). The initially formed was quenched with methanol (0.4mL). The solvent was removed

-
under reduced pressure and the residue was treated with 10 mL
Bu of Eb0. Water was added and the aqueous phase was acidified
1. MeLi to pH < 2with 10% HCl. The aqueous phase was extracted with
14a 34b + EbO, and the extracts were washed with water, brine, and then
2. nBul
dried ( N a a Q ) . The solventwas removed under reduced pressure
NPh and the crude product was recrystallized from methanol-water
giving 0.38 g (92%) of 8a: mp 121-124 "C; lH NMR 6 0.10 (s,
35a (R=n-Bu) 9H),0.13(s,9H),1.9-2.0(m,3H),5.32(bs,lH),5.66(bs,lH),
b (R = Me) 6.9-7.5 (m, 5 H); 13C NMR 6 -2.5,-1.4, 32.2,39.9,120.3,123.8,
butyl imidate ester 35a was converted into the corre- 124.4,128.8,138.4,151.5,172.5. Anal. Calcd for C1,HBNOSiz:
sponding methyl ester (35b) under the conditions used C, 63.89;H, 9.15;N, 4.38. Found C, 63.52;H, 9.07;N, 4.38.
for desilylation (NaOH-MeOH). The problem of over- Similarly prepared 8 b PTLC (1O:l CHZC12-EtOAc), 71 % ;
mp95.5-97.0OC;WNMR 60.07(s,18H),1.8-2.8(m,3H),4.36
alkylation results in part from the use of an excess of the (d, J = 5.8 Hz, 2 H), 5.31 (bs, 1 H), 5.60 (bs, 1 H), 7.25 (bs, 5 H);
alkylating agent which is required in most cases t o offset '3C NMR 6 -2.5,-1.4,32.2,38.7,43.7,124.4,127.2,128.0,128.5,
the excess nucleophile used in the standard conjugate 139.0,151.4,173.7. Anal. Calcd for ClsHaNOSiz: C, 64.80;H,
addition reaction procedure (Table 11). Thus while the 9.37;N, 4.20. Found: C, 64.56;H, 9.25;N, 4.30.
nucleophilicity of these tertiary a-silylated enolate dian- 8c: PTLC (1:lCH2ClTEtOAc),73 %;sublimed 75 "C (2mm):
ions appears lower than that of u n d y l a t e d amide dian- mp 113-115"C; lH NMR 6 0.09 (s,18H),1.8-2.5 (m, 3 H), 1.97
ions,% they are more reactive than the corresponding a-silyl (d, J = 2.7 Hz, 3 H), 5.32 (bs, 1 H), 5.58 (bs, 1 H); 13C NMR 6
carbonylate dianions which were found to be resistant to -2.5, 1.3, 26.2, 32.2, 38.9,124.2, 151.8, 174.7. Anal. Calcd for
a-alkylation under these conditions.6h ClzHnNOSi2: C, 55.97;H, 10.57;N, 5.44. Found C, 55.64;H,
10.26;N, 5.17.
Peterson Olefinations. Silyl dianions3 resulting from General Procedure for the Alkaline Desilylation of
conjugate addition reactions were found to readily con- a-Silylated Amides. N-Phenyl-4-(trimethylsilyl)-4-pente-
dense with pentanal and undergo Peterson-type olefination namide (9a). A solution containing 214 mg (0.67mmol) of 8a
reactions23 (Scheme V, Table IV). Yields were found to in 10 mL of MeOH was treated with 3 mL of 6 M NaOH and
be slightly better with lithium salts than with magnesium heated at reflux for 25 min. The solution wm cooled and the
salts. In all cases, mixtures of stereoisomeric olefins were methanol was removed under reduced pressure. The aqueous
obtained with t h e E-isomer predominating in most cases. solution was acidifed to pH < 2with 10% HCl and then extracted
The stereochemistry of isomeric olefins followed from lH with EbO. The extracts were washed with H2O and then brine,
dried (NazSOd), and concentrated. Recrystallization of the
NMR spectra where olefinic hydrogens cis to the carbonyl residue from pentane gave 143 mg (97%) of 9a: mp 51-53 "C;
. group in 2-isomers occur at lower field.27 1H NMR 6 0.11 (s,9H), 2.57 (bs, 4 HI, 5.43 (bs, 1 H), 5.62 (bs,
1H),6.9-7.6(m,5H),8.19(bs,1H);13CNMR6-1.54,31.0,36.6,
Experimental Section 120.4,124.2,128.8,138.3,150.9,171.4. Anal. Calcd for Cl4H21-
General. n-BuLi in hexane, tert-BuLi in pentane, PhLi in NOS: C, 67.96;H,8.56;N, 5.66. Found C, 67.83;H, 8.66;N,
cyclohexane-diethyl ether, n-BuMgC1, tert-BuMgC1, MeMgBr, 5.56.
~~
9b: bulb-to-bulb distillation (180"C, 0.1mm), 77% : lH NMR
(21) Homer,R.B.;Johuson,C.D.In TheChemistryofAmides;Zabicky, 60.08(~,9H),2.2-2.6(m,4H),4.4(d, J=5.7Hz,2H),5.36(bs,
J., Ed., Patai, S., Sr. Ed.;Interscience: New York, 1970; pp 734-764. 1 H), 5.54 (bs, 1 H), 5.75 (bs, 1 H), 7.27 (bs, 5 H); 13CNMR 6 -1.5,
(22) (a) Kaiser, E. M.; von Schriltz, D. M.; Hauser, C. R. J.Org. Chem. 31.2,35.9,43.7,124.2,127.5,127.8,128.7,138.6,151.1,172.4.Anal.
1968,33,4275. (b) Meyer, R. B.; Hauser, C. R. J. Org. Chem. 1961,26, Calcd for ClsHsNOSi: C, 68.91;H, 8.87;N, 53.6. Found C,
3696. (c) Meyer, R. B.; Hauser, C. R. J. Org. Chem. 1961,26,3187. (d)
Work, 5.D.; Bryant, D. R.; Hauser, C. R. J. Org. Chem. 1963,29, 722. 68.70; H, 8.67;H, 5.05.
(23) For reviews, see: (a) Peterson, D. J. Organomet. Chem. Rev. A 9c: bulb-to-bulb distillation (120OC, 1 mm), 91%; mp 12-15
1972, 7, 296. (b) Weber, W. P. Silicon Reagents for Organic Synthesis; "C;lHNMR60.09(~,9H),2.2-2.5(m,4H),2.79(d,J=4.6Hz,
Springer-Verlag: New York, 1983; pp 68-73. (c) Colvin, E. W. Silicon in 3 H), 5.36 (bs, 1 H), 5.54 (bs, 1 H); S
' C NMR: 6 -1.5, 26.2,31.2,
Organic Synthesis; Butterwortha: London, 1981; pp 141-162. (d) Ager,
D. J. Synthesis 1984, 384. (e) Ager, D. J. Org. React. (N. Y.)1990,38, 1. 35.9,124.1,151.2,173.4. Anal. Calcd for CBHlaOSi; C, 58.32;
(24) Brook, A. G.; Duff, J. M. Can. J. Chem. 1973,51, 2024. H,10.33;N, 7.56. Found: C, 57.67;H, 10.30;N, 7.35.
(26) Brook, A. G.;Duff, J. M.; hgrow, G. E. J. Organomet. Chem.
1976, 122, 31.
(26) Miller, R. B.; Al-Haman, M. I. J. Org. Chem. 1984,49, 725. (28) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(27) Leyden, D. E.; Cox, R. H. Analytical Applications fo NMR, John (29) Boechman,R.K.; Blum, D. M.; Ganem, B.;Halvey,N. Org. Synth.
Wiley & Son: New York, 1977; pp 166-167. 1978, 58, 152.
Charge-Directed Conjugate Addition Reactions J,Org. Chem., Vol. 58, No. 26, 1993 7479
Table 111. Tandem Conjugate Addition-Alkylation Reactions of 148 (Scheme IV)
entry RM E+ (equiv) alkylation conditions produ& (% yield)
1 MeLi Me1 (4) O°C,lh 33a (RN = RE = Me) (77)
2 Et1 (4) 0°C,4h 34a (RN = Me, RE = Et) (79)
3 n-BuI (4) 0 "C, 10 h 34b (RN= Me, RE = n-Bu) (52)b
4 n-BuLi Me1 (4) O°C,lh 33b (RN= n-Bu, RE = Me) (70)
34c (RN= n-Bu, RE = Me) (67)
5 Et1 (4) O°C,2h 34d (RN= n-Bu, RE = Et) (51)
6 n-BuMgC1 Me1 (4) 20°C,2h 33b (92)
7 MeMgCl Me1 (4) 20 "C,2 h 33a (81)
a Producta 34 were obtained by direct desilylation of 33 with NaOH, MeOH. b Bu(Et)CHC=NPh (OMe) was also isolated in 18%yield.

Scheme V HC1 and extracted with E h 0 . The ether extracts were washed

Ma - 1 . RM
2. nBuCHO
R

CONHPh
with HzO, dried (NazSOI), and concentrated. Recrystallization
of the residue from petroleum ether gave 417 mg (83%)of 148:
mp 74-75 O C ; 1H NMR 6 0.23 (s,9 H), 5.81 (d, J = 2.0 Hz, 1 H),
6.24(d,J = 2.0Hz, 1 H),7.0-7.7 (m,6H);13C NMR 6-1.4,120.2,
BU 1 124.2,128.9,130.0,138.3,151.4,169.9. Anal. Calcd for C12H1,-
NOSi: C,65.70; H, 7.81; N, 6.39. Found C, 65.41; H, 7.70; N,
6.28.
Table IV. Tandem Conjugate Addition-Peterson Similarly prepared from the appropriate isocyanate (Table I),
Olefination Reactions (Scheme V) 14b: 78%;mp 61.5-62.0 O C ; 1H NMR 6 0.17 (s,9 H), 4.39 (d, J
entry RM olefin (% yield) EIZ = 5.9 Hz, 2 H), 5.66 (d, J = 2.2 Hz, 1 H), 6.07 (d, J = 2.0 Hz, 1
H), 7.24 (bs, 5 H); '3C NMFk 6 -1.4, 43.5, 127.3, 127.6, 128.6,
1 n-BuMgC1 36a (57) 1:l 129.3,138.8,150.8,171.6. Anal. CalcdforClsHlsNOSi: C,66.90;
2 PhMgBr 36b (61) 2:l H, 8.21; N, 6.00. Found: C, 67.01; H, 8.12; N, 6.04.
3 n-BuLi 36a (70) 31 14c: 63%;bp69-71 "C (0.6mm);'HNMR60.17 (s,SH),2.83
4 PhLi 36b (77) 21 (d, J = 4.9 Hz, 3 H), 5.68 (d, J = 2.2 Hz, 1 H), 6.08 (d, J = 2.2
Hz, 1 H); l3C NMR 6 -1.4,26.2,129.3,150.8,172.7. Anal. Calcd
(E)-1-Iodo-1-(triphenylsily1)-1-hexene (19). A solution of for C7HlaNOSi: C, 53.45; H, 9.61; N, 8.90. Found C, 53.54; H,
l-(triphenylsilyl)-l-hexynem (3.40 g, 9.98 mmol) in anhydrous 9.75; N, 9.04.
EbO (15 mL) was treated dropwise with a 1.0 M solution of 2-(Trimethylsilyl)propenamide(14d). A solution of l-(tri-
diisobutylaluminum hydride (DlBAL) in hexane (10.3 mL, 10.3
mmol). The reaction was stirred overnight. The mixture was methyl~ily1)vinyllithium~~ was prepared by treating a solution
then cooled to -78 "C and treated oia cannula with a solution of containing 1.4 mL (9.1mmol) of 13 in 20 mL of THF at -78 O C
iodine (3.0g, 11 mmol) in anhydrous Eta0 (30 mL). After 15 min with 9.8 mL (18 mmol) of 1.8 M tert-BuLi in pentane. To this
at -78 "C,the mixture was allowed to warm to 20 "C,and the solution was added at -78 O C 1.4 g (10 mmol) of a trimethyleilyl
contents were poured into a beaker containing 10% HCl(25 mL) isocyanate (Aldrich) over 4 min. The solution was stirred for 70
and ice (100 g). After the ice had melted, the organic layer was min and then 1 mL of saturated NH4Cl solution was added. The
separated. The aqueous phase was extracted with pentane (75 mixture was warmed to 20 O C and concentrated under reduced
mL), and the combined organic extracts were washed with 10% pressure. The residue treated with 2 mL of H20 and 25 mL of
NaOH, 1.0 M NazSzOs (25 mL), and brine and then were dried EhO and the pH of the aqueous phase was adjusted to pH < 2
over NazSO4. After removal of the solvent, the crude product with 10%HC1. The aqueous phase was saturated with NaCl and
was recrystallized from petroleum ether giving 0.42 g (78%) of twice more extracted with EbO. The extracts were washed with
19: mp 66.5-68.0 O C ; 1H NMR 6 0.5-1.8 (b, 9 H), 5.26 (8, 1 H), HzO and then brine solution, dried (NaaSO4), and concentrated.
7.2-7.7 (m, 15 H); l3C NMR 6 13.6, 22.0, 30.6, 36.4, 98.0, 127.9, The residue was recrystallized from hexane giving 1.03 g (79%)
129.9,134.0, 136.2, 162.1. Anal. Calcd for C d d S i : C, 61.54; of 14d: mp 82-85 O C ; 1H NMR 6 0.19 (s,9 H), 5.74 (d, J = 2.0
H, 5.38. Found C, 61.66; H, 5.59. Hz, 1 H), 6.19 (d, J = 2.0 Hz, 1 H); 13CNMR 6 -1.4,130.5,150.1,
(2) -
- 1-1odo-1 (trimethylsily1)- 1,%butadiene (23). A solu- 174.2. Anal. Calcd for C&&lOSi: C, 50.30, H, 9.15; N, 9.78.
Found: C, 50.58; H, 9.33; N, 9.60.
tion containing 2.73 g (22 mmol) of 273' and 25 mL (25 mmol)
of 1 M DlBAH (in hexane) in 50 mL of EbO was allowed to stand General Method for the Preparation of Neutral Accep-
overnight and then cooled to -78 "C and treated with stirring, tors. N-Pheny1-(2)-2-(trimethylsilyl)-l-heptenamide (18).
over 2 min, with a solution containing 7.0 g (27 "01) of 12 in A solution containing (2)-1-trimethylsilyl-1-hexen-1-yllithiumm
50 mL of EhO. The mixture was stirred for 8 min and then was prepared by the addition of 3.1 mL (5 "01) of n-BuLi to
warmed to 20 "Cwhereupon an aqueous solution of NaHS03 was 1.41 g (5 mmol) of 1711in 20 mL of EbO at -78 "C. After 1 h,
added and stirring was continued until the solution was clear. freshly distilled phenyl isocyanate (0.6 mL, 5.5 mmol) was added
The mixture was diluted with pentane, washed sequentially with and stirring was continued for 1 h whereupon 0.25 mL of MeOH
water, 1 N HC1, water, and brine, and then dried over NazSQ4. was added and the mixture was allowed to warm to 20 "C.
The solution was concentrated on a steam bath and distilled Solvents were removed under reduced pressure, and the residue
(bulb-to-bulb, 130O C , 15 mm) giving 3.13 g (56%)of a 1:l mixture was treated with 10 mL of HzO and 25 mL of EbO. The aqueous
of 28 and 23. Upon standing for 0.5 h in sunlight, the mixture phase was acidified to pH < 2 by the addition of 10% HCl and
was 98 % 23 by capillary gas chromatographic analysis: lH NMR twice more extracted with EhO (25 mL). The extracts were
6 0.21 (s,9 H), 5.35 (m, 2 HI, 6.4-6.8 (m, 2 HI; 13CNMR 6 -1.5, washed with HzO and then brine solution and dried (NazSO4).
114.6, 122.1, 140.2, 144.1. Solvent removal gave a residue which was purified by PTLC
N-Phenyl-2-(trimethyleilyl)propenamide(14a). A solu- (CHZC12) giving 163 mg (76%) of 18 which was recrystallized
tion of approximately 0.6 M 5" in THF (9.1 mL, 5.5 mmol) was from 95% EtOH giving needles: mp 141-142"C (sublimes at 90
cooled to -78 "C and with stirring was treated dropwise with 0.25 OC, 1.5 mm); 1H NMR 6 0.25 (s, 9 H), 0.91 (t,J = 7.0 Hz, 3 H),
mL (2.3 mmol) of freshly distilled phenyl isocyanate. After 15 1.38(m,4H),2.18(m,2H),6.57(t,J=6.8Hz,lH),7.Q-7.6(m,
min, 0.4 mL of MeOH was added and the solvent was removed 6 H); I3C NMR 6 0.2, 13.9, 22.5, 31.5, 119.8, 124.0, 128.9, 138.4,
under reduced pressure. The residue was treated with water 141.3, 148.2, 171.7. Anal. Calcd for C&&JOSi: C, 69.76; H,
and the pH of the aqueous phase was adjusted to < 2 with 10% 9.15; N, 5.08. Found: C, 69.77; H, 9.45; N, 4.90. In a similar
manner the following unsaturated amides were prepared with
variations noted below and in Table I.
(30)Fitzmaurice, N. J.; Jackson, W. R.; Perlmutter, P. J.Organomet.
Chem. 1985,285,375.
(31) Bloremova, 0.N.; Volkova, L. I.; Maroshin, Y.V.; Kryazhev, Y. (32) GrBbel, B. T.; Seebach, D. Chem. Ber. 1977,110,867.
G. J. Gen. Chem. U.S.S.R. 1973,43, 1977. (33) Zweifel, G.; Lewis, W. J . Org. Chem. 1978, 43, 2739.
7480 J. Org. Chem., Vol. 58, No. 26, 1993 Cooke and Pollock
16: 2 equiv of tert-BuLi to 16%in THF; 65%: mp 156-158 (2.8 mmol) of n-BuLi to 360 mg (3.0 "01) of 1,3-dithianein 10
"C; 'H NMR 6 5.95 (d, J = 2.5 Hz, 1H), 6.94 (d, J = 2.5 Hz, 1 mL of THF, was cooled to -78 "C and treated with a solution
H), 6.8-7.8 (m, 20H); 13CNMR6 119.5,124.0,128.3,128.8,130.3, containing 215 mg (1.0 "01) of 14%in 3 mL of THF. After 1
132.4,136.2,137.8, 141.1,143.9,168.1. Anal. Calcd for CnHzs- min the mixture was warmed to 20 "C and after 4 h treated with
NOSt C, 79.96; H, 5.72; N, 3.45. Found C, 79.75; H, 5.64; N, 0.2 mL of MeOH. The solvent was removed under reduced
3.28. pressure and the residue was dissolved in 10 mL of MeOH and
2 0 69% from 5 1 hexane-EtOAc; mp 165-167 OC; 1H NMR heated under reflux whereupon 3 mL of 6 N NaOH was added
6 0.61 (t,J = 4.9 Hz, 3 H), 0.8-1.3 (b, 4 H), 1.6-2.0 (m, 2 H), and heating was continued for 25 min. The mixture was
6.9-7.8 (m, 22 H); 1gC NMR 6 13.6,22.2, 30.5,32.8, 119.8,123.8, concentrated under reduced pressure and the residue was treated
128.2,128.5,129.9,133.5,133.7,136.0,138.0,157.8,169.4. Anal. with 10 mL of EhO. The aqueous phase was adjusted to pH <
Calcd for CslHslNOSi: C, 80.65; H, 6.79; N, 3.03. Found C, 2 by the addition of 10% HCl and extracted with severalportions
80.47; H, 6.92; N, 3.05. of EhO. The extracta were dried (NaaSO4) and concentrated
22: 64% from 95% EtOH; mp 198.0-198.5 OC; lH NMR 6 0.29 and the residue purified by PTLC (1:l Et&-petroleum ether)
(~,9H),6.84(s,1H),7.34(m,11H);19CNMR6-1.6,120.1,124.2, giving, after recrystallization from EtOH-H20,30h as needles:
128.4,128.6,128.9,135.9,137.8,139.7,142.8,170.4. Anal. Calcd mp 116-117 OC; lH NMR 6 1.7-2.3 (m, 4 HI, 2.58 (t,J = 6.0 Hz,
for C&lNOSi: C, 73.17; H, 7.16; N, 4.74. Found C, 73.38; H, 2 H), 2.82 (dd, J = 6.8, 5.8 Hz, 4 H), 4.11 (t,J = 7.0 Hz, 1 H),
7.36; N, 4.52. 7.0-7.6 (m, 6H), 7.82 (bs, 1H); 13CNMR 6 25.9,29.9,30.7,34.1,
24: 79% from EtOH-H20: mp 161-162 "C; lH NMR 6 0.22 46.4, 120.0, 124.2, 129.0, 137.9, 170.3. Anal. Calcd for C18H17'
(8, 9 H), 5.2-5.5 (m, 2 H), 6.2-6.8 (m, 2 H), 7.1-7.7 (m, 5 H); 1sC NO&: C, 58.39; H, 6.41; N, 5.24. Found C, 58.44; H, 6.59; N,
NMR6-1.5,119.9,122.1,124.3,129.0,133.8,137.9,141.1,143.3, 5.11.
169.7. Anal. Calcd for C14HlsNOSi: C, 68.52; H, 7.80; N, 5.71. The following amides were prepared with additions as de-
Found C, 68.20; H, 7.82; N, 5.63. scribed above in the preparation of 29a followed directly by
26: 2 equiv of tert-BuLi to 26 in THF; 49 % from EtOH-H2O: desilylation as described above in the preparation of 30h. 30a:
mp 117-118 "C; lH NMR 6 0.23 (s,9 H), 0.7-1.5 (b, 10 HI, 2.0-2.4 92%; mp 94.0-96.5 "C (lit." mp 95 "C). 30b 94%; mp 95-97
(m, 4 H), 6.9-7.6 (m, 6 H); 13C NMR 6 0.3, 13.6, 14.0,23.1,27.4, "C (lit.% mp 97 "C). 30c: 71%; mp 105-107 "C mp 107-
30.9, 34.2, 11.98, 124.0, 129.0, 135.6, 138.1, 158.0, 171.6. Anal. 108 "C). 30d 73%; mp 90.5-92.5 "C (lit." mp 91.4-91.8 "C).
Calcd for Cl&NOSi: C, 71.23; H, 9.63; N, 4.61. Found C, 3Oe: 92%; mp 87-88 "C (lit.% mp 87-88 "C). 30f: 99%; .mp
71.36; H, 9.74; N, 4.59. 63-64 OC (lit.99mp 64 "C). 30g: 52%;mp 138.5-140.0 "C (ht."
Conjugate Addition Reactions (Table 11). Typical Pro- mp 139-140 "C). 30i: 91%; mp 84-86 "C (lit." mp 84-85 OC).
cedure. N-Phen y l-t- (trimethylsilyl)butanamide (29a) (en- 30j: 84%;mp 55-57 "C (lit.42 mp 55.0-55.5 "C). 30k: 61%; mp
try 1). Asolutioncontaining1.0mL (2.9mmol) of2.9MMeMgBr 60-62 "C (lit.& mp 62 "C). 301: 74%; n# = 1.4397 (lit." nD%
in ether in 3 mL of THF was cooled to -78 "C and treated dropwise = 1.4401).
with stirring with a solution containing 219 mg (1.0 mmol) of 14a 30m: 58%; PTLC (45:51 CHzClTEtOAc-HOAc); mp 41-43
in 3 mL of THF. After 1min the mixture was allowed to warm OC; lH NMR 6 0.8-2.0 (b, 11H), 2.20 (t,J = 7.0 Hz, 2 H), 2.78
to 20 "C where it was maintained for 4 h and then treated with (d, J = 4.9 Hz, 3 H), 6.55 (bs, 1H); 13CNMR 6 25.3,26.2, 32.2,
0.2 mL of MeOH. The solvent was removed under reduced 32.6, 35.9, 40.0, 174.3. This compound was identical to an
pressure and the residue was treated with water (10 mL) and authentic sample prepared from 3-cyclopentylpropanoylchloride
Eta0 (10 mL). The aqueous phase was acidified to pH = 2 by and MeNH2.
the addition 10% HCl and quickly extracted with EhO. The 3011:70%;PTLC (101CH2ClrEtOAc);mp 53-55 "C; 'H NMR
extracts were washed with water and then brine solution, dried 6 0.89 (8, 9 H), 1.51 (t,J = 11.0 Hz, 2 H), 2.15 (t, J = 11.0 Hz,
(NazSOd),and concentrated giving, after recrystallization from 2 H), 2.79 (d, J = 4.9 Hz, 3 H), 5.50 (bs, 1 H); 18CNMR 6 26.3,
petroleum ether, 201 mg (89%)of 29a which was sublimed at 65 29.1,30.1,32.2,39.6,174.5.Anal. Calcd for C&17NO C, 67.09;
OC (0.2 mm): mp 96-98 "C; lH NMR 6 0.10 (8, 9 H), 0.97 (t, J H, 11.96; N, 9.78. Found: C, 67.12; H, 11.61; N, 9.50.
= 6.5 Hz, 3 H), 1.1-1.9 (m, 3 H), 7.0-7.7 (m, 5 H); 13CNMR 6 30p: 30%; mp 94.0-94.5 "C (lit."mp 94 "C). 30q: 69%; mp
-2.6,15.0,20.6,43.0,120.3,123.8,128.8,138.4,173.7. Anal. Calcd 102-104 "C (lit.& mp 103 "C).
for C81H21NOSi: C, 66.33; H, 8.99; N, 5.95. Found C, 66.48; H, 30t: 93%; PTLC (CH2Cl2); mp 52-55 "C; lH NMR 6 0.85 (t,
9.06; N, 5.88. J = 4.7 Hz, 6 H), 1.24 (b, 12 H), 2.0 (bs, 1 H), 2.26 (d, J = 6.5
Similarly prepared with the variations noted below and in Hz, 2 H), 6.8-7.4 (m,5 H), 8.49 (bs, 1H); 18CNMR 6 14.1,23.0,
Table 11,29b: 83%;PTLC (CH2C12); mp 159-161 "C; 'H NMR 28.8,33.6,35.4,42.7,120.4,124.0,128.7,138.4,172.2. Anal. Calcd
6 0.16 (8, 9 H), 2.14 (dd, J = 2.9,ll.O Hz, 1H), 2.72 (dd, J = 2.9, for C17HnNO: C, 78.11; H, 10.41; N, 5.36. Found C, 78.13; H,
14.0Hz, lH),3.28(dd, J = 11.0,14.0Hz, 1H),3.28(dd, J = 11.0, 10.41; N, 5.29.
14.0Hz,1H),7.0-7.4(m,11H);1aCNMR6-2.6,33.2,43.4,120.3, 30u: 52%;PTLC (CH2C12);mp 92-93 "C (lit."mp 93-94 "C).
123.9,126.0,128.2,128.5,128.8,138.1,142.4,172.6. Anal. Calcd Additions to Alkali Metal Salts of 14a. Typical Example
for ClJ3aNOSi: C, 72.68; H, 7.79; N, 4.71. Found C, 72.61; H, with a Sodium Salt. NaH (60 mg, 1.5 mmol), previously freed
7.86; N, 4.90. of oil by washing with pentane, was suspended in 3 mL of THF.
29c: 88%;PTLC (CH2C12);mp 144.0-144.5 "C; lH NMR 6 A solution containing 219 mg (1.0 mmol) of 14a in 3 mL of THF
0.10(~,9H),0.25-2.0(b,12H),7.0-7.5(m,6H);~~CNMR6-2.6, was added and the mixture stirred for 1h. Vigorous H2 evolution
25.2, 16.3, 32.3, 33.1, 33.6, 40.3, 40.8, 120.3, 123.8, 128.4, 138.6, was observed. The mixture was cooled to -78 "C and treated
173.6. Anal. Calcd for C1,HnNOSi: C, 70.53; H, 9.40; N, 4.84. with 0.45 mL (0.9 "01) of n-BuMgC1. After 5 min, the
Found C, 70.94; H, 9.42; N, 4.92. temperature was raised to -15 OC where it was maintained for
29d 91 %; PTLC (CH2C12);sublimed 75 "C(1mm); mp EM-87 1 h. MeOH (0.2 mL) was then added and the mixture was
OC; 1H NMR 6 0.11 (8, 9 H), 1.9-2.7 (m, 3 H), 4.8-5.0 (m, 2 H),
5.6-6.0(m,1H),6.9-7.3(m,5H),7.81(bs,1H);1gCNMR6-2.5, (35) Shriner, R. L.; Fuson, R. C.; Curtin, D.Y.; M o d , T. C. The
31.2, 40.2, 115.1, 120.5, 123.8, 128.7, 138.0, 138.4, 173.1. Anal. Systematic Identification of Organic Compounds, 6th ed.; J. Wiley &
Calcd for C14H2lNOSi: C, 67.97; H, 8.56; N, 5.66. Found C, Sone: New York, 1980, pp 538-539.
67.58; H, 8.41; N, 5.70. (36) Dieckmann, W.; Hoppe, J.; Stein,R. Chem. Ber. 1904,37,4627.
29k 78%; PTLC (1O:l CH2ClTEtOAc); 'H NMR 6 0.10 (8,9 (37) Tanida, H.; Kyo, Y. Chem. Abstr. 1966,64, 1980.
H), 1.97 (dd, J = 3.2, 11.2 Hz, 1 H), 2.62 (d, J = 4.6 Hz, 3 H), (38) Yukawa, Y.; Hanafuea, T.; Kurita, H. Mem. Zmt. Sci. Z n d . Res.
Osaka Uniu. 1966,12, 147-161 (Chem. Abstr. 1956,50,15410b).
2.7-3.3 (m, 2 H), 5.61 (bs, 1H), 7.16 (be, 5 H); 13CNMR 6 -2.6, (39) h a n o , M.J. Pharm. SOC.Jpn. 1922,480,97.
26.0, 33.3, 42.1, 125.9, 128.3, 142.7, 174.7. (40)Bartlett, P. D.;Stilee, M. J. Am. Chem. SOC.1955, 77, 2806.
Additions with Desilylation. Typical Procedure. (41) Demer, 0. C.; King, J. J. Org. Chem. 1943,8, 168.
N-Phenyl-3-[2-(1,3-dithianyl)]propanamide (30h). A solu- (42) Ficini, J. Bull. SOC.Chim. Fr. 1954, 1367.
tion of 2-lithio-1,3-dithiane," prepared by the addition of 1.7 mL (43) Suzuki, I.; Tsuboi, M Shimanouchi, T. Spectrochim. Acta 1960,
16, 467.
(44) D'Alelio, G. F.; Reid, E. E. J. Am. Chem. SOC.1937,69, 109.
(34) Seebach, D.;Beck, A. K. Organic Syntheses; Wiley: New York, (45) Taveme, M.H. I. Rec. Trau. Chim. Pays-Baa 1897,16, 263.
1988; Collect. Vol. 6, p 316. (46) Bott, K. Chem. Ber. 1967,100,2791.
Charge-Directed Conjugate Addition Reactions J. Org. Chem., Vol. 58, No. 26, 1993 7481
subjected to the standard workup and desilylation procedure 67%; PTLC (CHSC12); mp 83-85 "C; 1H NMR 6 0.84 (t,J = 5.9
(previouslydescribed inthe preparation of 3Oh) givingafter PTLC Hz, 3 H), 1.1-1.9 (m, 11H), 2.1-2.6 (m, 1H), 6.9-7.7 (m, 5 H),
( 4 1 CH&l&tOAc) 70 mg (37 % ) of 30f. A more-polar byprod- 8.49 (bs, 1H); W NMR 6 14.0,18.0,22.5,27.2,31.9,34.5,42.2,
uct, N-phenyl-3-methoxypropanamide, resulting from MeOH 120.4,124.0,128.7,138.4,176.0. Anal. Calcd for ClrH2lNO C,
addition to unreacted 148 was also isolated: mp 40-42 OC; lH 76.67; H, 9.65; N, 6.39. Found C, 76.73; H, 9.64, N, 6.44. 34d
NMR 6 2.57 (t,J = 5.9 Hz, 2 H), 3.33 (8, 3 H), 3.67 (t, J = 5.9 50%; PTLC (CH2C12);bulb-to-bulb distillation 160 "C, 0.6 mm;
Hz, 2 H),7.32 (m, 5 H), 8.53 (be, 1H); W NMR 6 37.6, 58.3, 1H NMR 6 0.7-2.4 (b, 17 H), 6.9-7.7 (m, 5 H), 8.60 (be, 1H);
68.4, 120.0, 120.8, 128.5, 138.0, 169.7. Anal. Calcd for C&U- NMR 6 12.0, 14.1, 22.6,26.2,27.4,32.0, 33.0, 50.1, 120.6,124.1,
NO2: C, 67.02; H, 7.31; N, 7.82. found C, 66.81; H, 7.41; N, 7.75. 128.7,138.3,175.3. Anal. CalcdforC&=NO C,77.21;H,9.93;
Additions to potassium salts (from KH) were conducted in a N, 6.00. Found C, 77.21; H, 9.94; N, 5.80.
s i m i i manner. Tandem Conjugate Addition-Peterson Olefination. Typ-
Tandem Addition-Alkylation Reactions. Typical Pro- ical Procedure. N-Phenyl-2-pentylheptanamide.To a 80-
cedure (Table 111). N-Phenyl-2-methyl-2-(trimethy lsily1) - lution containing 1.5 mL (3.0 "01) of 2.0 M n-BuMgCl in 6 mL
butanamide (338). To a solution containing 1.8 mL (3.0 m o l ) of THF at -78 O C was added dropwise 222 mg (1.0 "01) of 148
of 1.6 N MeLi (EhO) in 5 mL of THF at -78 "C was added 217 in 3 mL of THF. After 1min, the mixture was allowed to warm
mg (1.0 "01) of 14a in 3 mL of THF. After 1 min the to 20 OC where it was kept for 2 h. The mixture was then cooled
temperature was allowed to warm to 20 OC where it was to -78 O C and treated with 0.32 mL (3 "01) of freshly distilled
maintained for 1h. The mixture was then cooled to -78 "C and pentanal. The solution was allowed to warm to 20 "C and then
0.25 mL (4.0 "01) of Me1 was added and the mixture kept at heatedat4MSOCfor 100min. After solventremoval,thereidue
0 OC for 1h. HOAc (0.18 mL) wae added and a standard workup was treated with 10 mL of EhO and 10 mL of H20. The aqueous
(aee 29a) with PTLC (CH2Cl2) gave 190 mg (77%) of 338: mp layer was acidified with 10% HCl to pH 6 2 and twice more
74-76 O C ; 'H NMR 6 0.08 (8, 9 H), 0.91 (t,J 3 6.9 Hz, 3 H), 1.25 extracted with EhO. The extracts were washed with HpO and
(8, 3 H), 1.3-2.3 (m, 2 H), 7.0-7.5 (m, 5 H); lSCNMR 6 -3.8,9.0, then brine, dried (NaBO41, and concentrated. PTLC (CH&ld
15.9,26.9,38.1,120.3,123.8,128.7,138.3,174.9. Desilyationgave of the residue gave 67 mg (61%) of 36a ae a 1:l mixture of E / Z
known N-phenyl-2-methyIb~tanamide.~~ isomers. The E-isomer contained a triplet at 6 6.25 (J = 7.3 Hz)
Similarly prepared (with variations noted in Table III),33b and the 2-isomer a triplet of 6 5.50 for the olefinic proton in its
70% PTLC (CH2Cl2); sublimes at 60 OC (0.2 mm); mp 62-64 "C; 'H NMR spectrum. Reduction of this mixture with HZ(10 mg
'H NMR 6 0.08 (s,9 H), 0.87 (t,J = 6.4 Hz, 3 HI, 1.28 (be,10 H), PtOz, 2 mL EtOAc, 3 h at 1 atm Ha) gave 61 mg (92%) of
2.0 (bs,1H), 7.24 (m,6 H); '*C NMR 6 -3.8,14.1,16.6,22.6,24.4, N-phenyl-2-pentylheptamide: mp 86.5-87.5 O C ; lH NMR: 6
32.5,34.4,37.8,120.1,123.9,128.9,138.3,175.0. Anal. Calcdfor 0.7-1.8 (m, 22 H), 2.1-2.4 (b, 1H), 6.9-7.7 (m, 5 H), 8.02 (be, 1
C1,HaOSi: C, 70.04; H, 10.03; N, 4.80. Found C, 70.35; H, H); l*C NMR d 14.0, 22.5, 27.4, 32.0, 33.3, 48.9, 120.3, 124.0,
10.04, N, 4.78. 128.8,138.2,175.0. Anal. CalcdforCl&&JO:C,78.49;H,10.61;
34a: 79%;PTLC (CH2C12):mp 124-126 OC (lit."mp 126-127 N, 5.09. Found C, 78.51; H, 10.79; N, 5.11. Similarly prepared
OC). 34b 52%; PTLC (CHgC12): mp 87-89 OC (lit." mp 88-89 was N-phenyl-2-benzylheptanamide:mp 97-98 OC (1it.m mp 98
"C). 36b 18%;1H NMR 6 0.7-1.7 (m, 14 H), 2.1-2.5 (m, 1H), OC).
3.76 (a, 3 H), 6.6-7.4 (m, 5 HI; lacNMR 6 12.2,13.9 22.7, 26.0,
29.9, 32.5, 41.6, 52.9, 121.4, 122.3, 128.7, 148.7, 165.3. 36b was Acknowledgment. We thank the National Science
identical to an authentic sample prepared by the 0-methylation Foundation for their support of this work.
of N-phenyl-2-ethylhexamide with dimethyl sulfate.& 34c:
(49)Biihner, A. Liebigs Ann. Chem. 1904,333,289.
(47)Holbert, J. M.J. Am. Phorm. Aseoc. 1946,35, 315. (50) Naik, R G.;Shah, M.T.;Narguad, K.S.J. Univ. Bombay, Sect.
(48)Skinner, G.S.;Perkins, J. F. J. Am. Chem. SOC.1960, 72, 5669. A, Part 3 1950,9,54 (Chem. Abstr. 1950,46, 11124i).