Conjugate additions of a simple monosilylcopper reagent with use of the CuI-DMS complex: Stereoselectivities and a dramatic impact by DMS

Article abstract of DOI:10.1021/jo048269e

(Chemical Equation Presented) Conjugate additions utilizing the simple monosilylcuprate reagent Li[PhMe₂SiCuI] to α,β-unsaturated carbonyl compounds are described. The presence of dimethyl sulfide (DMS), either as a component originating from t

Full text of DOI:10.1021/jo048269e

Conjugate Additions of a Simple Monosilylcopper Reagent with
Use of the CuI‚DMS Complex: Stereoselectivities and a Dramatic
Impact by DMS
Jesse Dambacher and Mikael Bergdahl*
Department of Chemistry and Biochemistry, San Diego State University,
San Diego, California, 92182-1030
bergdahl@sciences.sdsu.edu
Received October 1, 2004
Conjugate additions utilizing the simple monosilylcuprate reagent Li[PhMe2SiCuI] to R,â-
unsaturated carbonyl compounds are described. The presence of dimethyl sulfide (DMS), either as
a component originating from the (CuI)4(DMS)3 complex or as a solvent added, has an amazing
influence on both chemical yield and the level of diastereomeric ratio (dr) of the products. Gilman-
type silylcyanocuprates {Li(Ph2MeSi)2Cu/LiCN} have previously been used to guarantee good results
in conjugate addition reactions. External additives such as HMPA, tributylphosphine, or dialkylzinc
are not necessary in conjunction with the simple Li[PhMe2SiCuI] reagent. It is demonstrated that
the monosilylcuprate reagent with DMS as the solvent is very useful with sterically hindered (â,â-
disubstituted) enones, and provides very high yields of the â-silylated 1,4-addition products. Since
there is no oligomerization problem associated with the simple monosilylcuprate reagent, this
reagent should be considered as a very useful 1,4-silyl donor to enals, enones, and enoates in
conjugate addition reactions.
Introduction
silyl (Me2PhSi) group is probably one of the most useful
because the carbon-silicon bond can be replaced under
mild oxidative conditions (Tamao-Fleming)2,3 to make
the corresponding alcohols with complete retention of
stereochemistry.2a Thus, creating a carbon-silicon bond
with a predominantly high asymmetric induction at the
â-carbonyl position serves as a complementary synthetic
tool in the making of enantiomerically pure acetate aldol
products.4
Since the pioneering work by Fleming in the
early 1980s,5 the dimethylphenylsilylcyanocuprate re-
agent, depicted either as (PhMe2Si)2CuLi‚LiCN6 or
(PhMe2Si)2Cu(CN)Li2, has been used extensively in the
majority of conjugate additions to make â-silylated car-
bonyl compounds.5b The corresponding monosilylcu-
prate reagents, represented either as PhMe2SiCu/LiX or
Li[PhMe2SiCuX],7 possess a better economy of group
Organosilanes have fundamental roles in organic
chemistry and synthesis, particularly as control moieties
for stereochemistry in chemical transformations,1 or as
key intermediates to introduce the hydroxy function.2
Formation of the silicon-carbon bond from the conjugate
addition of a suitable silyl cuprate reagent to an R,â-
unsaturated carbonyl compound is an excellent surro-
gate for the acetate aldol reaction. Although there are
various silyl substituents available, the dimethylphenyl-
* To whom correspondence should be addressed. Phone: (619) 594-
5865. Fax: (619) 594-4634.
(1) (a) Colvin, E. W. Silicon in Organic Synthesis; Butterworths:
London, UK, 1981. (b) Webber, W. P. Silicon Reagents in Organic
Synthesis, Springer: Berlin, Germany, 1983. (c) Colvin, E. W. Silicon
Reagents in Organic Synthesis; Academic Press: Orlando, FL, 1988.
(d) Brook, M. A. Silicon in Organic, Organometallic and Polymer
Chemistry; Wiley: New York, 2000. (e) Fleming, I.; Barbero, A.; Walter,
D. Chem. Rev. 1997, 97, 2063-2192.
(2) (a) Fleming, I.; Henning, R.; Plaut, H. J. Chem. Soc., Chem.
(3) (a) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. Organome-
tallics 1983, 2, 1694-1696. (b) Tamao, K.; Tanaka, T.; Nakajima, T.;
Sumiya, R.; Arai, H.; Ito, Y. Tetrahedron Lett. 1986, 27, 3377-3380.
(c) Tamao, K.; Kawachi, A.; Ito, Y. J. Am. Chem. Soc. 1992, 114, 3989-
3990.
Commun.,
I 1984, 29-31. (b) Fleming, I.; Sanderson, P. E. J.
Tetrahedron Lett. 1987, 28, 4229-4232. (c) Fleming, I.; Henning, R.;
Parker, D. C.; Plaut, H. E.; Sanderson, P. E. J. J. Chem. Soc., Perkin
Trans. 1 1995, 317-337.
10.1021/jo048269e CCC: $30.25 © 2005 American Chemical Society
Published on Web 12/23/2004
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J. Org. Chem. 2005, 70, 580-589

Conjugate Additions of a Simple Monosilylcopper Reagent
transfer, but their inherent lower stability, solubility, and
reactivity have limited their widespread use as reliable
reagents for the formation of â-silylated carbonyl prod-
ucts. Such problems are sometimes solved by taking
advantage of additives such as tributylphosphine8a or
HMPA.8b Dialkylzinc9 has also been used to form the
milder discrete silylzincates from the corresponding
lithium reagents, which allows for catalytic quantities
of CuCN to be used.10a The “Gilman-type” cyanocuprates
utilize 2 equiv of the silyllithium reagent, as opposed to
1 equiv relative to CuCN in the monosilylcuprate.
Examples of the monosilylcuprate reagents used in
conjugate additions are rare,11 and most accounts support
the idea that these reagents are not as useful as “Gilman-
type” silylcyanocuprates.12
equiv of the (CuI)4(SMe2)3 complex (CuI‚0.75DMS) in
THF. Specifically, we reported that dimethyl sulfide
purified CuI is an instrumental component in obtaining
very high yields as well as exceptional levels of stereo-
selectivity compared to what has previously been re-
ported with the (PhMe2Si)2CuLi‚LiCN reagent. We also
demonstrated that external additives such as tribu-
tylphosphine, HMPA, or dialkylzinc are unnecessary,
even though less of the silyllithium reagent was needed14
to obtain high yields as well as diastereoselectivities of
the â-silylated carbonyl products. Similar asymmetric
studies with the (PhMe2Si)2CuLi‚LiCN system in conju-
gate additions have been carried out to R,â-unsaturated
esters,15a N-enoylsultams,8a,15b R-alkylidenelactones,16 R,â-
unsaturatedoxazolidines,15a andN-enoylpyrrolidinones,9b,15ac
most commonly in conjunction with additives to increase
the magnitude of π-facial selectivity. In support of our
asymmetric additions to chiral N-enoyloxazolidinones17a
or pyrrolidinones,17b we found that the less complex
reagent, Li[PhMe2SiCuI], needs no external additives or
Lewis acids, other than the dimethyl sulfide derived from
the CuI‚0.75DMS complex, to generate very high yields
and diastereomeric ratios.13
We now extend the scope of the CuI‚0.75DMS pro-
moted conjugate additions of the monosilylcuprate re-
agent to R,â-unsaturated substrates. Most importantly,
with regard to applications in asymmetric synthesis, we
present a variety of highly diastereoselective reactions
applying the Li[PhMe2SiCuI] reagent, followed by the
Tamao-Fleming mild oxidation protocol2,3 for the prepa-
ration of acetate aldol products in excellent optical
purities. Finally, we introduce a nice solution to previous
problems associated with sterically congested â,â-disub-
stituted enones and their reactivity in 1,4-additions of
the Li[PhMe2SiCuI] reagent.
In contrast to these notions, quite recently we in-
troduced a very versatile monosilylcuprate reagent,
Li[PhMe2SiCuI],13 based on 1 equiv of PhMe2SiLi and 1
(4) Reviews on asymmetric acetate aldol reactions, see: (a) Masam-
une, S.; Choy, W.; Petersen, J. S.; Sita, L. R. Angew. Chem., Int. Ed.
Engl. 1985, 24, 1-30. (b) Braun, M. Angew. Chem., Int. Ed. Engl. 1987,
26, 24-37. Articles on auxiliary based asymmetric acetate aldol
reactions, see: (c) Oppolzer, W.; Starkemann, C. Tetrahedron Lett.
1992, 33, 2439-2442. (d) Helmchen, G.; Leikauf, U.; Taufer-Kno¨pfel,
I. Angew. Chem., Int. Ed. Engl. 1985, 24, 874-875. (e) Bond, S.;
Perlmutter, P. J. Org. Chem. 1997, 62, 6397-6400. (f) Palomo, C.;
Gonza´lez, A.; Garc´ıa, J. M.; Landa, C.; Oiarbide, M.; Rodr´ıguez, S.;
Linden, A. Angew. Chem., Int. Ed. 1998, 37, 180-182. Articles on chiral
metal complexes in acetate aldol reactions, see: (g) Masamune, S.;
Sato, T.; Kim, B.-M.; Wollman, T. A. J. Am. Chem. Soc. 1986, 108,
8279-8281. (h) Duthaler, R. O.; Herold, P.; Lottenbach, W.; Oertle,
K.; Riediker, M. Angew. Chem. Int. Ed. Engl. 1989, 28, 495-497. (i)
Corey, E. J.; Imwinkelried, R.; Pikul, S.; Xiang, Y. B. J. Am. Chem.
Soc. 1989, 111, 5493-5495. Articles on tin-enolates in acetate aldol
reactions, see: (j) Nagao, Y.; Yamada, S.; Kumagai, T.; Ochiai, M.;
Fujita, E. J. Chem. Soc., Chem. Commun. 1985, 1418-1419. (k) Ryu,
I.; Murai, S.; Sonoda, N. J. Org. Chem. 1986, 51, 2391-2393. Articles
on lithium-enolates in acetate aldol reactions, see: (l) Braun, M.;
Devant, R. Tetrahedron Lett. 1984, 25, 5031-5034. (m) Devant, R.;
Mahler, U.; Braun, M. Chem. Ber. 1988, 121, 397-406. (n) Saito, S.;
Hatanaka, K.; Kano, T.; Yamamoto, H. Angew. Chem., Int. Ed. 1998,
37, 3378-3381. Articles on boron-enolates in acetate aldol reac-
tions, see: (o) Yan, T.-H.; Hung, A.-W.; Lee, H.-C.; Chang, C.-S. J. Org.
Chem. 1994, 59, 8187-8191. (p) Zhang, Y.; Phillips, A. J.; Sammakia,
T. Org. Lett. 2004, 6, 23-25. Articles on titanium-enolates in ace-
tate aldol reactions, see: (q) Yan, T.-H.; Hung, A.-W.; Lee, H.-C.;
Chang, C.-S.; Liu, W.-H. J. Org. Chem. 1995, 60, 3301-3306.
(r) Gonza´lez, AÄ .; Aiguade´, J.; Urp´ı, F.; Vilarrasa, J. Tetrahedron Lett.
1996, 37, 8949-8952. (s) Guz, N. R.; Phillips, A. J. Org. Lett. 2002, 4,
2253-2256. (t) Hodge, M. B.; Olivo, H. F. Tetrahedron 2004, 60, 9397-
9403.
(5) (a) Ager, D. J.; Fleming, I.; Patel, S. K. J. Chem. Soc., Perkin
Trans. 1 1981, 2520-2526. (b) Fleming I. in Organocopper Reagents-A
Practical Approach; Taylor, R. J. K., Ed.; Oxford University Press:
Oxford, UK, 1994; pp 267-292 and references therein. (c) Perlmutter
P. Conjugate Addition Reactions in Organic Synthesis: Pergamon
Press: Oxford, UK, 1992.
(6) The silylcyanocuprate should be indicated as the “Gilman-type”
reagent, see: Bertz, S. H.; Miao, G.; Eriksson, M. Chem. Commun.
1996, 815-816. See also: Lipshutz, B. H.; James, B. J. Org. Chem.
1994, 59, 7585-7587.
(7) Although there is no evidence for a Cu-X bond, the silylhalo-
cuprate reagent is tentatively depicted as the favorable “Gilman-type”
reagent: Li[PhMe2CuX].
(8) (a) Palomo, C.; Aizpurua, J. M.; Iturburu, M.; Urchegui, R. J.
Org. Chem. 1994, 59, 240-244. (b) Takaki, K.; Maeda, T.; Ishikawa,
M. J. Org. Chem. 1989, 54, 58-62.
(9) (a) Tu¨ckmantel, W.; Oshima, K.; Nozaki, H. Chem. Ber. 1986,
119, 1581-1593. (b) Crump, R. A. N. C.; Fleming, I.; Urch, C. J. J.
Chem. Soc., Perkin Trans. 1 1994, 701-706. (c) MacLean, B. L.;
Hennigar, K. A.; Kells, K. W.; Singer, R. D. Tetrahedron Lett. 1997,
38, 7313-7316.
(10) (a) Lipshutz, B. H.; Sclafani, J. A.; Takanami, T. J. Am. Chem.
Soc. 1998, 120, 4021-4022. For some other developments of 1,4-
additions of silyl groups, see: (b) Hale, M. R.; Hoveyda, A. H. J. Org.
Chem. 1994, 59, 4370-4374. (c) Ito, H.; Ishizuka, T.; Tateiwa, J.-I.;
Sonada, M.; Hosomi, A. J. Am. Chem. Soc. 1998, 120, 11196-11197.
(c) Lee, T. W.; Corey, E. J. Org. Lett. 2001, 3, 3337-3339.
Results and Discussion
Conjugate addition reactions with the Li[PhMe2SiCuI]
reagent have been shown13 to work perfectly on a variety
of R,â-unsaturated substrates, including ketones, alde-
hydes, esters, imides, and even a primary amide to pro-
vide extraordinarily good yields as well as high stereo-
selectivities of the products. The Li[PhMe2SiCuI] reagent
is prepared from 1 equiv of the dark red PhMe2SiLi
reagent18 and 1.2 equiv19 of the CuI‚0.75DMS complex20
(11) (a) Sharma, S.; Oehlschlager, A. C. Tetrahedron 1989, 45, 557-
568. (b) Sharma, S.; Oehlschlager, A. C. J. Org. Chem. 1991, 56, 770-
776.
(12) Dieter, R. K. In Modern Organocopper Chemistry; Krause, N.,
Ed.; Wiley-VCH: Weinheim, Germany, 2002; pp 79-144.
(13) Dambacher, J.; Bergdahl, M. Chem. Commun. 2003, 144-145.
(14) Typically, 1.4-2.0 equiv of Li[PhMe2SiCuI] (∼60 mM in THF)
was employed.
(15) (a) Fleming. I.; Kindon, N. D. J. Chem. Soc., Perkin Trans. 1
1995, 303-315. (b) Oppolzer, W.; Mills, R. J.; Pachinger, W.; Stevenson,
T. Helv. Chim. Acta 1986, 69, 1542-1545. (c) Fleming, I.; Kindon, N.
D. J. Chem. Soc., Chem. Commun. 1987, 1177-1179.
(16) (a) Amberg, W.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1988,
27, 1718-1719. (b) Amberg, W.; Seebach, D. Chem. Ber. 1990, 123,
2439-2444.
(17) (a) Nicola´s, E.; Russel, K. C.; Hruby, V. J. J. Org. Chem. 1993,
58, 766-770. (b) Tomioka, K.; Suenaga, T.; Koga, K. Tetrahedron Lett.
1986, 27, 369-372.
(18) See ref 5b, p 260.
(19) Molar equivalents calculated for pure (CuI)4(Me2S)3, so as to
avoid formation of the corresponding homocuprate (PhMe2Si)2CuLi/
LiI. For a discussion on trialkylsilylcuprate formation, see: Sharma,
S.; Oehlschlager, A. C. J. Org. Chem. 1989, 54, 5383-5387.
J. Org. Chem, Vol. 70, No. 2, 2005 581

Dambacher and Bergdahl
TABLE 1. Influence by DMS and THF on Asymmetric 1,4-Additions
a Obtained from 1 equiv of PhMe2SiLi and 1.2 equiv of CuI‚0.75DMS. b Based on isolated, purified, and characterized material.
c Diastereomeric ratio measured on crude material, using 1H NMR, 500 MHz. d Yield and dr based on isolation of the major diastereomer.
e 99.999% reagent purity CuI (Aldrich). f 0.75 equiv added to 99.999% CuI. g TBDPS ) tert-butyldiphenylsilyl.
in an appropriate solvent at -78 °C. Although the
Li[PhMe2SiCuI] reagent is sensitive to elevated temper-
atures, the presence of DMS seems to have a stabilizing
effect21 on the silylcopper reagent. Thus, the substrates
are exposed to the Li[PhMe2SiCuI] reagent at -78 °C,
and subsequently the reaction temperature is increased
to -20 °C during 5-8 h. The efficiency of the heteroge-
neous brown Li[PhMe2SiCuI] reagent in THF is dramati-
cally improved at low temperatures. The loss of activity
of silylcopper reagent is clearly visible when the color of
the reagent turns gray-black, accentuated at higher
temperatures. The active Li[PhMe2SiCuI] reagent is
stable for many hours at -78 °C. Once the reaction
temperature has reached approximately -20 °C, the
organocopper reaction is quenched by the addition of
aqueous NH4Cl/NH3. Results of the asymmetric conjugate
additions of the Li[PhMe2SiCuI] reagent to various
optically active imides employing THF or DMS as a
medium are illustrated in Table 1.
Several research groups have utilized organocopper
reagents in asymmetric 1,4-additions to optically active
imides, such as the N-enoyl-substituted oxazolidinones17a,22
and pyrrolidinones.15c,17b Recently we reported the
Li[RCuI]/TMSI combination to the same substrates
where it was found that the sense of stereochemistry
obtained was extremely dependent on Lewis acids as well
as the medium.22i Although TMS-halides are very popu-
lar additives for increasing the rate of 1,4-addition
reactions using organocopper reagents, we specifically
found that this additive is not a participant in the critical
steps in Et2O. The role of TMSI in THF, on the other
hand, is tremendously important. The same sense of
π-facial stereochemistry is obtained in THF by using
Li[BuCuI] as the Li[PhMe2SiCuI] reagent, using the
same chiral imide. The level of diastereomeric ratio (dr)
with Li[PhMe2SiCuI] in THF is 99:1 (entry 1) while the
dr with Li[BuCuI] in the same medium was significantly
lower (3:1).22j Intuitively it appears the size of the copper
reagent might play a crucial role on the stereochemical
outcome, but the reactivity of the reagent is equally
important. While 2 equiv of the Li[PhMe2SiCuI] reagent
to imide 1 initially was used, it is feasible to use much
less silylcopper reagent (∼1.3 equiv versus imide) in THF
and still maintain a high yield and good stereoselectivity.
It is also possible to use DMS as a solvent in the
conjugate addition of the Li[PhMe2SiCuI] reagent to
imide 1. The presence of DMS has remarkable effects on
the rate, stability, and selectivity of the conjugate addi-
tion of the monosilylcuprate reagent (Table 1).23 In
(22) (a) Wipf, P.; Xu, W.; Smitrovich, H.; Lehmann, R.; Venanzi, L.
M. Tetrahedron 1994, 50, 1935-1954. (b) Lou, B.-S.; Li, G.; Lung, F.-
D.; Hruby, V. J. J. Org. Chem. 1995, 60, 5509-5514. (c) Qian, X.;
Russel, K. C.; Boteju, L. W.; Hruby, V. J. Tetrahedron 1995, 51, 1033-
1054. (d) Wipf, P.; Takahashi, H. Chem. Commun. 1996, 2675-2676.
(e) Andersson, P. G.; Schink, H. E.; O¨ sterlund, K. J. Org. Chem. 1998,
63, 8067-8070. (f) Williams, D. R.; Kissel, W. S.; Li, J. J. Tetrahedron
Lett. 1998, 39, 8593-8596. (g) Schneider, C.; Reese, O. Synthesis 2000,
1689-1694. (h) Pollock, P.; Dambacher, J.; Anness, R.; Bergdahl, M.
Tetrahedron Lett. 2002, 43, 3693-3697. (i) Dambacher, J.; Bergdahl,
M. Org. Lett. 2003, 5, 3539-3541. (j) Dambacher, J.; Anness, R.;
Pollock, P.; Bergdahl, M. Tetrahedron 2004, 60, 2097-2110. (k)
Williams, D. R.; Nold, A. L.; Mullins, R. J. J. Org. Chem. 2004, 69,
5374-5382.
(20) For a discussion on the stability of the CuI/DMS complex, see:
Eriksson, M.; Hjelmencrantz, A.; Nilsson, M.; Olsson, T. Tetrahedron
1995, 51, 12631-12644. See also: Eriksson, M.; Iliefski, T.; Nilsson,
M.; Olsson, T. J. Org. Chem. 1997, 62, 182-187.
(23) A similar observation has been reported by Bertz using the
Li[BuCuI] reagent in the conjugate addition to 2-cyclohexenone, see
ref 21.
(21) Bertz, S.; Dabbagh, G. Tetrahedron 1989, 45, 425-434.
582 J. Org. Chem., Vol. 70, No. 2, 2005

Conjugate Additions of a Simple Monosilylcopper Reagent
SCHEME 1
contrast to THF and Et2O, the CuI‚0.75DMS dissolved
in DMS and gave a homogeneous dark brown color of
Li[PhMe2SiCuI] after the addition of PhMe2SiLi at -78
°C. The Li[PhMe2SiCuI] reagent in DMS reacts faster
with the imides than in THF. Thus, product 5 was
obtained in 94% (dr ) 94:6) if the silylcuprate addition
to imide 1 was conducted in DMS at -78 °C for 12 h.
Due to the favorable Li-THF coordination, the reac-
tion temperature was slowly increased to -20 °C over
7 h. Employing 1.4 equiv of the Li[PhMe2SiCuI] re-
agent in DMS gave 91% yield of product 5 (dr ) 94:6)
(entry 4) while a considerably higher dr is obtained in
THF (entry 1). In comparison, the phenylglycine-derived
oxazolidinone (1) is considerably more efficient in block-
ing one π-face during the conjugate addition of the
Li[PhMe2SiCuI] reagent than the corresponding tert-
leucine-derived oxazolidinone 2 (entry 6). The absolute
stereochemistry of the created â-silyl carbon was deter-
mined by using the optical rotation of the corresponding
â-silyl carboxylic acid15a obtained after removal of the
chiral auxiliary with LiOH in THF.
The influence of the DMS, derived from the
CuI‚0.75DMS complex, in the conjugate addition of
Li[PhMe2SiCuI] is instrumental. Thus, the CuI purified
via its DMS complex is of fundamental importance for
the Li[PhMe2SiCuI] reagent to undergo an efficient
conjugate addition. The influence of DMS on yield as well
as stereoselectivity is demonstrated for the 1,4-additions
of Li[PhMe2SiCuI] to Koga’s 2-pyrrolidinone (Table 1).13
Employing imide 3 and the Li[PhMe2SiCuI] reagent
obtained from ultrapure grade CuI,24 in the absence of
DMS, not only drastically reduced the yield of 7 from 92%
to 63%, it also completely degraded the dr from 92%25 to
an insignificant level (entry 8). Once DMS was introduced
with ultrapure grade CuI (entry 9), the yield as well as
the ratio of the â-silylated product increased significantly.
As it was impossible to restore the level of dr (96:4) by
adding DMS, it is likely that the Cu(I) quality is indeed
also a variable. DMS remaining from the purification of
CuI is partly a constituent responsible for the higher
yield, probably due to a more soluble and increasingly
reactive silylcopper species. Although we have reported
monumental differences between CuI‚0.75DMS and
CuBr‚DMS complex applied in promoting catalytic 1,4-
additions of alkenyl groups from vinylzirconocenes rela-
tive to the transfer of the corresponding alkyl groups,26
the difference between iodide and bromide ligands in this
study utilizing PhMe2SiLi in THF is less important.
Thus, conjugate addition of Li[PhMe2SiCuX] to the silyl
protected 2-pyrrolidinone 4, using either CuI‚0.75DMS
(entry 10) or the CuBr‚DMS complex (entry 11), provided
excellent yields as well as matching diastereomeric ratios
of product 8.
pathway), a detailed mechanistic explanation has not yet
emerged. However, it is generally accepted that the initial
lithium-carbonyl coordination is a first critical step in
conjugate additions of organocuprate reagents.27 Al-
though the mechanistic details of the organocopper
reactions are very elusive, a qualitative pattern with the
Li[PhMe2SiCuI] reagent in asymmetric 1,4-additions is
becoming apparent. Thus, a lithium species is proposed
to initially chelate the carbonyl groups preceding the
formation of the copper π-complex, allowing the silyl
addition to occur to the most available π-face of the imide
while adopting a syn-s-cis conformation (Scheme 1). Since
the nature of the responsible silylcopper species depicted
that forms the π-complex28 is unknown, there is the
possibility for dimer29 and higher oligomer formations.30
The distinctive power of the Li[PhMe2SiCuI] as a
reagent in asymmetric conjugate additions to various
N-enoyl-2-oxazolidinones is illustrated (Table 2). The
conjugate addition of the “PhMe2Si” group is proposed
to proceed via the syn-s-cis imide conformation based on
the stereochemistry introduced as well as the built-in
chirality of the 2-oxazolidinone moiety. Not only is the
chemical yield almost quantitative for the 1,4-additions
employing the monosilylcopper reagent, but also the
diastereomeric ratios are very high. Specifically the
phenylglycine-derived oxazolidinone (12) was most ef-
ficient in favoring one π-face for the 1,4-additions, using
the silylcuprate reagent obtained from the CuI‚0.75DMS
complex (entry 12). Although the yield of 18 was excellent
when employing the CuBr‚DMS complex, the stereose-
lectivity decreased (entry 13). Oxazolidinone (12) has
previously been found to be an excellent auxiliary for
other organocopper systems.16a,22 In contrast to our
results, it has been reported that tributylphosphine was
“imperative” for the Li[PhMe2SiCuI] reagent to undergo
a conjugate addition to imide 12, even at 0 °C.8a In the
same report, the corresponding Li[(PhMe2Si)2Cu]LiCN
reagent was reported to give only ∼50% de to sub-
strate 12 and ∼20% de employing imide 13. In compari-
son, CuI‚0.75DMS generated Li[PhMe2SiCuI] reagent is
very efficient with tert-leucine-derived imides (14-16) or
with the phenylalanine derivative (13) without any
external additives such as HMPA or tributylphosphine.
(27) The presence of powerful electrophiles (e.g., TMSI or TMSOTf)
can compete with lithium as the initial “activator” in conjugate
additions of Li[RCuI], see ref 22j. See also: (a) Bergdahl, M.; Lindstedt,
E.-L.; Nilsson, M.; Olsson, T. Tetrahedron 1988, 44, 2055-2062. (b)
Bergdahl, M.; Lindstedt, E.-L.; Olsson, T. J. Organomet. Chem. 1989,
365, c11-14. (c) Bergdahl, M.; Nilsson, M.; Olsson, T.; Stern, K.
Tetrahedron 1991, 47, 9691-9702. (d) Bergdahl, M.; Iliefski, T.;
Nilsson, M.; Olsson, T. Tetrahedron Lett. 1995, 36, 3227-3230.
(28) For a recent NMR study on π-complex formation, see: Bertz,
S. H.; Carlin, C. M.; Deadwyler, D. A.; Murphy, M. D.; Ogle, C. A.;
Seagle, P. H. J. Am. Chem. Soc. 2002, 124, 13650-13651.
(29) Nakamura, E.; Mori, S.; Morokuma, K. J. Am. Chem. Soc. 1998,
120, 8273-8274.
Because of the uncertainty of many variables in
organocopper reactions (e.g., cuprate structures, addi-
tives, solvents, reaction conditions, and substrate, as well
as the cuprate cluster at each stage of the reaction
(24) Reagent purity grade (99.999%) CuI purchased from Aldrich.
(25) The absolute stereochemistry at the â-silyl carbon was deter-
mined by integration of the two methyl doublet peaks {δ 1.02 (minor
isomer) and 0.94 ppm (major isomer)} in the 1H NMR spectrum, see
ref 15a.
(26) El-Batta, A.; Hage, T.; Plotkin, S.; Bergdahl, M. Org. Lett. 2004,
6, 107-110.
(30) Olmstead, M.; Power, P. P.; J. Am. Chem. Soc. 1990, 112, 8008-
8014.
J. Org. Chem, Vol. 70, No. 2, 2005 583

Dambacher and Bergdahl
TABLE 2. Asymmetric Li[PhMe2SiCuX] Additions
tive substrates. Our results employing the simple
Li[PhMe2SiCuI] reagent obtained from CuI‚0.75DMS are
exceptional, not only with respect to levels of stereose-
lectivity but also chemical yield. The fact that excellent
chemical yields also were obtained with R,â-unsaturated
aldehydes and ketones (Table 3) implies that there is
little, if any, oligomerization occurring, which normally
is a common side reaction associated with more reactive
enals and enones with Gilman-type cuprate reagents.
Moreover, the monosilylcuprate reagent underwent very
efficient conjugate additions to enoates (entries 22 and
25). As the Li[PhMe2SiCuI] reagent reacted with an R,â-
unsaturated amide to give the product (26) in 60% yield
(entry 21), it is feasible to conduct the 1,4-addition in the
presence of fairly acidic moieties.
Large substituents surrounding the â-carbon in the
enone are known to influence the rate of the addition of
Li[PhMe2SiCuI]. Thus, conjugate addition of the monosi-
lylcuprate reagent conducted in THF to 3-methyl-2-
cyclopentenone (entry 32) provided only 5% of product
35 with a significant amount of recovered enone. The 1,4-
addition to 2-cyclopentenone, on the other hand, provided
99% of 34 (entry 31). Since it is recognized that coordi-
nating media like THF decrease the rate of the conjugate
additions and that DMS at the same time increases the
rate, stability, and selectivity with use of alkylcopper
reagents,21 it was intuitive to assess the influence of DMS
as a solvent on the conjugate addition of Li[PhMe2SiCuI]
to â,â-disubstituted enones. Indeed, it was possible to
obtain very high yields of product 35 and 36 starting from
â,â-disubstituted cyclic enones and Li[PhMe2SiCuI] in
DMS as the solvent. Similarly, mesityloxide (entry 28)
provided an excellent yield of product 31 (entry 28) when
the reaction was conducted in DMS, while the similar
reaction in THF only provided 5% of 31 (entry 27) and a
considerable amount of unconsumed enone.
The influence of DMS on the rate of the addition of
Li[PhMe2SiCuI] to a 2-ene-4-ynoate (32) was also scru-
tinized. Consequently, if the reaction of Li[PhMe2SiCuI]
and 32 was conducted in THF at -78 °C for 4 h, 45% of
product 33 was obtained (entry 29). Despite the presence
of the electron-rich alkyne attached on the â-position, the
yield increased to 78% of the â-silylated product 33 if the
reaction was conducted in DMS at -78 °C. In this
context, it should be mentioned that Gilman-type cu-
prates (R2CuLi/LiI and R2CuLi/LiCN) have been re-
ported33 to prefer the 1,6-addition pathway instead of the
1,4-addition to a 2-ene-4-ynoate. In contrast, the conju-
gate addition with the Li[PhMe2SiCuI] reagent in DMS
to 32 has an extraordinary preference (entry 30) for the
1,4-addition pathway.34
a Reactions were conducted in THF with purified CuI‚0.75 DMS
complex. b Characterized by NMR (1H and 13C), IR, and MS.
Diastereomeric ratios determined on the crude material by high-
resolution 1H NMR (500 MHz). c Based on isolated and purified
material. d Purified CuBr‚DMS employed, dr = 93:7.
It has also been reported8a that Oppolzer’s31 N-enoylsul-
tam provides very high diastereomeric ratios employing
the Li[(PhMe2Si)2Cu]LiCN reagent. However, as a sig-
nificant contrast, the same N-crotonylsultam exerted an
extremely poor diastereoselectivity (∼10%) in THF utiliz-
ing the Li[PhMe2SiCuI] reagent obtained from DMS
purified CuI.
Due to the efficiency of the phenylglycine-derived
auxiliary (12) to differentiate between the two π-faces
despite the ability for free rotation of the phenyl group,
attention was also paid to the corresponding more rigid
indanol auxiliary32 (entry 18). Surprisingly, the indanol
(17) auxiliary displays a less efficient π-face discrimina-
tion than the corresponding phenylglycine-, phenylala-
nine-, and tert-leucine-derived auxiliaries in the conjugate
addition of Li[PhMe2SiCuI] in THF.
The most desirable application of a â-SiMe2Ph carbonyl
compound comes from its subsequent oxidation to a
hydroxyl group, a reaction sequence that proceeds via
retention of configuration at the â-carbon. Thus, oxidation
of the phenylsilane (Table 1) with mercuric ion in an
acetic acid solution of peracetic acid2b provides excellent
yields of the enantiomerically pure acetate aldol products
9, 10, and 11. Fleming5b has described this powerful
transformation in great detail. Hence the key phenylsi-
The monosilylcuprate reagent, Li[PhMe2SiCuI], is
mild enough to work in the presence of fairly sensi-
(31) (a) Oppolzer, W. Tetrahedron 1987, 43, 1969-2004. (b) Op-
polzer, W. Pure Appl. Chem. 1988, 60, 39-48.
(32) (a) Ghosh, A.; Duong, T.; McKee, S. J. Chem. Soc., Chem
Commun. 1992, 1673-1674. (b) Senanayake, C. H. Aldrichim. Acta
1998, 31, 3-15.
(33) Krause, N.; Thorand, S. Inorg. Chim. Acta 1999, 296, 1-11.
See also: Gerold, A.; Krause, N. Chem. Ber. 1994, 127, 1547-1549.
(34) No 1,6-addition product could be detected.
584 J. Org. Chem., Vol. 70, No. 2, 2005

Conjugate Additions of a Simple Monosilylcopper Reagent
TABLE 3. 1,4-Additions of Monosilylcopper Reagents
a Reactions conducted with purified CuI‚0.75DMS complex. 1.4-2.0 equiv versus substrate. 1.2 equiv of “Cu” versus 1.0 equiv of silyl
lithium reagent. Reaction temperature maintained at -78 °C for 4 h, increased toward 0 °C over 7 h. b Characterized by NMR (1H and
13C), IR, and MS. c Based on isolated and purified material. d Reaction quenched at -78 °C after 4 h.
lane has to first react with an electrophile, in which the
resulting activated phenyl ring is removed by nucleophilic
attack of a peracetate anion, followed by a rearrangement
that resembles the well-known oxidation of a borane with
a peroxide.
in conjunction with the CuI‚0.75DMS complex either
gave decomposition or low yields of the 1,4-addition prod-
ucts. The Li[Ph2MeSiCuI] reagent reacts readily with an
enone in THF (entry 26). Also in this case, utilizing the
Li[Ph2MeSiCuI] reagent and an enoate, a good yield of
product 28 was obtained if the reaction was conducted
in DMS (entry 24).
Regardless of the electrophile used in the initial attack
of the PhMe2Si group, alkenes present will react faster
than the disconnection of the phenyl ring from the
silyl group. In this scenario, synthesis of a propargylic
alcohol from silane 33 utilizing the Tamao-Fleming
protocol would be fruitless. Since other silanes have
been found readily oxidized to the corresponding alco-
hols, and thus more applicable for synthesis, several
attempts were made to differentiate the substituents
attached on the silicon atom in the monosilylcuprate
reagent utilizing the CuI‚0.75DMS complex. Specifically
the Li[(Et2N)Ph2SiCuI] reagent3c,5b was attempted be-
cause the silicon already has a nucleophilic group pres-
ent that can be removed under basic oxidative condi-
tions. Attempted monosilylcuprates generated from, e.g.,
Ph2MeSiLi,35 t-BuPh2SiLi,36 or (Et2N)Ph2SiLi5b in THF
Conclusions
This paper illustrates that excellent yields and levels
of stereoselectivity can be obtained by utilizing the
monosilylcuprate reagent, Li[PhMe2SiCuI], generated
from the CuI‚0.75DMS complex. It is highly recom-
mended that the CuI be purified via its DMS complex
prior to making the monosilylcuprate reagent in THF or
DMS as solvents. This study also shows that the monosi-
lylcuprate reagent is both more stable and more reactive
with DMS as solvent. In this context, it is possible to
utilize the monosilylcuprate reagent with sterically hin-
dered (â,â-disubstituted) enones and still maintain a high
(35) Chen, H.-M.; Oliver, J. P. J. Organomet. Chem. 1986, 316, 255-
260.
(36) Barbero, A.; Cuadrado, P.; Gonza´lez, A. M. J. Chem. Soc., Perkin
Trans. 1 1991, 2811-2816.
J. Org. Chem, Vol. 70, No. 2, 2005 585

Dambacher and Bergdahl
purified with flash chromatography (30% Et2O in pentane, Rf
0.40) to give an 80% (943 mg) yield of 1 as a white solid; mp
99-102 °C; [R]20D +131.0 (c 1.0, CH2Cl2) {lit.38 mp 103.0-104.0
yield of the 1,4-addition products. We have clearly
demonstrated that the presence of external additives
such as tributylphosphine, HMPA, or dialkylzinc is
unnecessary even though 1 equiv of the silyllithium
reagent relative to the CuI‚0.75DMS complex is em-
ployed. Although the corresponding silylzincates can be
used to avoid oligomerization of â-silyl enolates, we have
furthermore demonstrated that the monosilylcuprate
reagent can be adopted successfully since there are no
oligomerization problems observed during the 1,4-addi-
tion reactions. Employing the simple Li[PhMe2SiCuI]
reagent obtained from CuI‚0.75DMS is an attractive
alternative to CuCN. The monosilylcopper system is
anticipated to be a very useful reagent in the formation
of silicon-carbon bonds in organic synthesis. Further
development of other monosilylcopper systems will be
reported from our laboratory.
°C; [R]20 +103.1 (c 1.0, CHCl3)}. H NMR (500 MHz, CDCl3)
1
D
δ 7.41-7.31 (m, Ar-H, 5H), 7.23 (dd, CHCHCO, J ) 15.4, 1.3
Hz, 1H), 7.07 (dd, CHCHCO, J ) 15.4, 6.8 Hz, 1H), 5.50 (dd,
NCH, J ) 8.8, 3.9 Hz, 1H), 4.70 (t, OCH2, J ) 8.8 Hz, 1H),
4.28 (dd, OCH2, J ) 8.8, 3.9 Hz, 1H), 2.53 (m, (CH3)2CH, 1H),
1.09, 1.08 (2d, (CH3)2CH, J ) 6.8 Hz each, 3H each); 13C NMR
(125 MHz, CDCl3) δ 165.0, 158.1, 153.7, 139.2, 129.2 (2C),
128.6, 126.0 (2C), 117.7, 69.9, 57.8, 31.5, 21.2(2C); FTIR (cm-1
)
2964, 1771, 1686, 1635; MS m/z 259 (M+, 63%), 216 (M - C3H7,
8%), 162 (M - C6H9O, 5%), 96 (100%), 77 (C6H5, 19%); HRMS
(EI) calcd for [C15H17NO3] 259.1208, found 259.1201.
N-(4′-Methyl-2′-pentenoyl)-4S-tert-butyl-1,3-oxazolidin-
2-one (2). Butyllithium (2.5 M in hexane, 0.92 mL, 2.3 mmol,
1.1 equiv) was added to a solution of 4S-tert-butyl-1,3-oxazo-
lidin-2-one (2.1 mmol, 300 mg) in THF (10 mL) at -78 °C
under argon. The resulting mixture was stirred for 45 min and
a solution of freshly distilled trans-4-methyl-2-pentenoyl chlo-
ride (1.2 equiv, 2.5 mmol) in THF (5 mL) was added via syringe
at -78 °C. The reaction mixture was stirred for an additional
30 min at -78 °C and then warmed to ambient temperature.
Saturated aqueous ammonium chloride (1 mL) was added to
the mixture and then diluted with water (30 mL). After
extraction with ether (3 × 30 mL), the combined organics were
dried over MgSO4, filtered, and evaporated. The crude product
was purified with flash chromatography (15% Et2O in pentane,
Experimental Section
Typical Procedure for 1,4-Additions of Monosilylcu-
prate Reagents: Preparation of Compounds 5-8, 18-31,
33-36. The Li[PhMe2SiCuI] reagent was prepared from
PhMe2SiLi5b (0.986 mmol, 1 equiv) and purified CuI‚0.75DMS37
complex (1.2 equiv) at -78 °C in anhydrous THF (10 mL), or
alternatively in anhydrous DMS (10 mL). The resulting dark
brown slurry was stirred 20 min at -78 °C, and the appropri-
ate substrate (0.5-0.8 equiv) dissolved in THF or DMS (7-10
mL) was added via the reaction flask wall at -78 °C, using a
gastight syringe. In THF, the reaction mixture was stirred for
2 h at -78 °C and then allowed to rise to about -20 °C over
the next 7 h before a saturated solution of NH4Cl/NH3 (pH
∼10) was added (5 mL). In DMS, depending on the reactivity
of the substrate, the reaction temperature was maintained at
-78 °C and subsequently quenched at this low temperature.
After increasing the temperature to +20 °C and removing the
septum, the resulting mixture was stirred until a homogeneous
deep blue solution was obtained. The mixture was then poured
out in mixture of Et2O (25 mL) and water (25 mL) and
transferred to a separation funnel. The aqueous phase was
extracted with Et2O (3 × 25 mL) and the combined organic
layers dried over MgSO4. After removal of the solvent, the
crude material was dried and the diasteromeric ratio was
determined with 1H NMR spectroscopy. The crude product was
subsequently purified with chromatography on a silica gel
column.
Typical Procedure for Preparation of Acetate Aldol
Products (9-11):2c Oxidation of Silanes 5, 6, and 8. The
appropriate silane (400 µmol, 1 equiv) and Hg(OAc)2 (420 µmol)
in 32% peracetic acid in acetic acid (4 mL) was stirred at room
temperature for 5 h. Ether (80 mL) was added and the mixture
was transferred to a separation funnel. The organic layer was
washed with sodium thiosulfate (1.0 M, 50 mL), water (50 mL),
sodium bicarbonate (2.0 M, 50 mL), and brine (50 mL) and
dried over anhydrous magnesium sulfate. The organic solvent
was removed under vacuum and the diastereomeric ratio was
determined on the crude material with 1H NMR spectroscopy.
Purification of the crude acetate aldol products and enrichment
of the major diasteromer for compounds 9-11 were conducted
by using flash chromatography on silica gel.
Rf 0.25) to give a 60% (301 mg) yield of 2 as a clear oil; [R]20
D
+85.0 (c 0.10, CH2Cl2). 1H NMR (500 MHz, CDCl3) δ 7.21 (dd,
CHCHCO, J ) 15.4, 1.3 Hz, 1H), 7.09 (dd, CHCHCO, J ) 15.4,
6.7 Hz, 1H), 4.50 (dd, NCH, J ) 7.6, 1.7 Hz, 1H), 4.28 (dd,
OCH2, J ) 9.3, 1.7 Hz, 1H), 4.23 (dd, OCH2, J ) 9.3, 7.6 Hz,
1H), 2.54 (m, (CH3)2CH, 1H), 1.10, 1.08 (2d, (CH3)2CH, J )
6.8 Hz each, 3H each), 0.94 (s, t-Bu, 9H); 13C NMR (125 MHz,
CDCl3) δ 165.7, 157.6, 154.7, 117.9, 65.2, 60.8, 35.9, 31.5, 25.6
(3C), 21.3 (2C); FTIR (film, cm-1) 2965, 1782, 1689, 1635; MS
m/z 239 (M+, 11%), 224 (M - CH3, 7%), 196 (M - C3H7, 8%),
97 (M - C7H12NO2, 100%), 57 (C4H9, 12%); HRMS (EI) calcd
for [C13H21NO3] 239.1521, found 239.1514.
N-(2′E-Butenoyl)-5S-tert-butyldiphenylsilyloxymethyl-
2-pyrrolidinone (4). Butyllithium (2.5 M in hexane, 1.40 mL,
3.50 mmol, 1.2 equiv) was added to a solution of 5S-tert-
butyldiphenylsilyloxymethyl-2-pyrrolidinone40 (2.83 mmol, 1.0
g) in THF (10 mL) at -78 °C under argon. The resulting
mixture was stirred for 45 min and a solution of freshly
distilled trans-crotonyl chloride (2.83 mmol, 1.0 equiv) in THF
(5 mL) was added via syringe at -78 °C. The reaction mixture
was stirred for an additional 30 min at -78 °C and then
warmed to ambient temperature. Saturated aqueous am-
monium chloride (1 mL) was added to the mixture and then
diluted with water (30 mL). After extraction with ether (3 ×
30 mL), the combined organics were dried over MgSO4, filtered,
and evaporated. The crude product was purified with flash
chromatography (30% Et2O in pentane, Rf 0.40) to give an 87%
(1.03 g) yield of 4 as a white solid; mp 115-117 °C, [R]20D -65.5
1
(c 1.0, CH2Cl2). H NMR (500 MHz, CDCl3) δ 7.66-7.62 (m,
Ar-H, 2H), 7.57-7.55 (m, Ar-H, 2H), 7.46-7.37 (m, Ar-H, 4H),
7.36-7.32 (m, partly hidden, Ar-H, 2H), 7.32 (dq, partly
hidden, CHCHCH3, J ) 15.2, 1.6 Hz 1H), 7.09 (dq, CHCHCH3,
J ) 15.2, 7.0, 1H), 4.51 (m, NCH, 1H), 3.99 (dd, OCH2, J )
10.6, 3.7 Hz, 1H), 3.74 (dd, OCH2, J ) 10.6, 2.3 Hz, 1H), 2.92
(ddd, J ) 17.7, 10.5, 10.5 Hz, COCH2-ring, 1H), 2.50 (m,
COCH2-ring, 1H), 2.13 (m, CH2-ring, 2H), 1.98 (dd, CHCHCH3,
J ) 7.0, 1.6 Hz, 3H), 1.05 (s, Si-t-Bu, 9H); 13C NMR δ 176.4,
165.9, 145.5, 135.6 (2C), 135.5 (2C), 133.1, 132.8, 129.82,
129.80, 127.8 (2C), 127.7 (2C), 124.1, 64.7, 58.0, 33.4, 26.8 (3C),
21.0, 19.2, 18.5; FTIR (cm-1) 2958, 1736, 1680, 1637, 1336,
1112, 704; MS m/z 422 (M+, 1%), 406 (M - CH3, 1%), 364 (M
N-(4′-Methyl-2′-pentenoyl)-4S-phenyl-1,3-oxazolidin-2-
one (1).38 1 was obtained from an acylation reaction39 with
4S-phenyl-1,3-oxazolidin-2-one, butyllithium, and trans-4-
methyl-2-pentenoyl chloride in THF. The crude product was
(37) House, H. O.; Chu, C.-Y.; Wilkins, J. M.; Umen, M. J. Org.
Chem. 1975, 40, 1460-1469. See also ref 20.
(38) Liao, S.; Shenderovich, M. D.; Lin, J.; Hruby, V. J. Tetrahedron
1997, 53, 16645-16662.
(39) Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem. Soc. 1981,
103, 2127-2129.
(40) Obtained in 92% yield from the silylation of the alcohol, using
TBDPSCl and imidazole in DMF.
586 J. Org. Chem., Vol. 70, No. 2, 2005

Conjugate Additions of a Simple Monosilylcopper Reagent
- C4H9, 100%), 296 (20%), 266 (17%), 236 (15%), 218 (40%),
181 (M - C16H19Si, 8%), 69 (C4H5O, 20%); HRMS (EI, DCI/
NH3) calcd for [C25H32NO3Si]+ (MH+) 422.2151, found 422.2144.
176.3, 174.3, 138.0, 135.7, 134.2, 133.4, 133.0, 130.0, 129.2,
128.0, 65.0, 58.0, 39.3, 33.4, 27.0, 21.3, 19.4, 15.6, 14.6, -4.7,
-4.9; FTIR (film, cm-1) 1736, 1690; HRMS (EI) calcd for
[C33H44NO3Si2]+ (MH+) 558.2860, found 558.2838. Anal. Calcd
for C33H43NO3Si2: C, 71.05; H, 7.77; N, 2.51. Found: C, 70.83;
H, 8.04; N, 2.46.
N-(3′S-Dimethylphenylsilyl-4′-methylpentanoyl)-4S-
phenyl-1,3-oxazolidin-2-one (5). 5 was obtained from a
reaction between substrate 1 and Li[Me2PhSiCuI] in THF. The
crude product was purified with flash chromatography (15%
Et2O in pentane, Rf 0.25) to give 84% (163 mg, 99:1 dr) of 5 as
a clear oil. 1H NMR (500 MHz, CDCl3) δ 7.49-7.47 (m, Ar-H,
2H), 7.40-7.29 (m, Ar-H, 6H), 7.23-7.21 (m, Ar-H, 2H), 5.18
(dd, NCH, J ) 8.7, 3.7 Hz, 1H), 4.55 (t, OCH2, J ) 8.8 Hz,
1H), 4.20 (dd, OCH2, J ) 8.8, 3.7 Hz, 1H), 3.13 (dd, COCH2, J
) 17.2, 7.3 Hz, 1H), 2.85 (dd, COCH2, J ) 17.2, 6.4 Hz, 1H),
1.86 (m, (CH3)2CH, 1H), 1.63 (m, SiCH, 1H), 0.88, 0.82 (2d,
(CH3)2CH, J ) 6.8 Hz, 3H each), 0.28, 0.27 (2s, Si(CH3)2, 3H
each); 13C NMR δ 173.4, 153.6, 139.2, 139.1, 134.0 (2C), 129.1
(2C), 128.7, 128.6, 127.6 (2C), 125.9 (2C), 69.9, 57.7, 33.2, 28.8,
27.8, 22.6, 21.1, -2.3, -3.1; FTIR (film, cm-1) 1786, 1705; MS
m/z 395 (M+, 3%), 380 (M - CH3, 40%), 352 (M - C3H7, 85%),
298 (60%), 135 (PhSiMe2, 100%); HRMS (EI, DCI/NH3) calcd
for [C23H30NO3Si]+ (MH+) 396.1995, found 396.1981.
N-(3′S-Hydroxy-4′-methylpentanoyl)-4S-phenyl-1,3-
oxazolidin-2-one (9).46 Obtained from the oxidation of silane
5 using Hg(OAc)2 and peracetic acid. The crude product was
purified using flash chromatography (50% Et2O in pentane,
Rf 0.20 for the major diasteromer) to give a 77% (71 mg, >99:1
dr) yield of 9 as a white solid; mp 93-94 °C (lit.46 mp 86.0 °C).
1H NMR (500 MHz, CDCl3) δ 7.42-7.33 (m, Ar-H, 3H), 7.32-
7.28 (m, Ar-H, 2H), 5.46 (dd, NCH, J ) 8.7, 3.6 Hz, 1H), 4.71
(dd, OCH2, J ) 8.9, 8.7 Hz, 1H), 4.28 (dd, OCH2, J ) 8.9, 3.6
Hz, 1H), 3.81 (m, HOCH, 1H), 3.15 (dd, COCH2, J ) 17.0, 2.7
Hz, 1H), 3.07 (dd, COCH2, J ) 17.0, 9.6 Hz, 1H), 2.70 (br s,
OH, 1H), 1.74 (m, (CH3)2CH, 1H), 0.96 (2d, (CH3)2CH, J ) 6.1
Hz, 6H); 13C NMR δ 172.8, 153.8, 138.7, 129.3 (2C), 128.8,
125.7 (2C), 72.7, 70.1, 57.6, 39.9, 33.3, 18.4, 17.7; FTIR (cm-1
)
3522, 1782, 1703; MS m/z 259 (M - H2O, 25%), 234 (M - C3H7,
83%), 164 (100%). HRMS (DEI) calcd for [C15H20NO4]+ (MH+)
278.1392, found 278.1390.
N-(3′S-Dimethylphenylsilyl-4′-methylpentanoyl)-4S-
tert-butyl-1,3-oxazolidin-2-one (6). 6 was obtained from a
reaction between substrate 2 and Li[Me2PhSiCuI] in THF. The
crude product was purified with flash chromatography (15%
Et2O in pentane, Rf 0.40) to give an 87% (161 mg, 96:4 dr)
N-(3′S-Hydroxy-4′-methylpentanoyl)-4S-tert-butyl-1,3-
oxazolidin-2-one (10). Obtained from the oxidation of silane
6 using Hg(OAc)2 and peracetic acid. The crude product was
purified using flash chromatography (30% Et2O in pentane,
Rf 0.20 for the major diastereomer) to give a 77% (74 mg, >99:1
1
yield of 6 as a white solid; mp 82-85 °C. H NMR (500 MHz,
CDCl3) δ 7.56-7.53 (m, Ar-H, 2H), 7.35-7.32 (m, Ar-H, 3H),
4.31 (dd, NCH, J ) 7.7, 1.6 Hz, 1H), 4.21 (dd, OCH2, J ) 9.3,
1.6 Hz, 1H), 4.09 (dd, OCH2, J ) 9.3, 7.7 Hz, 1H), 3.17 (dd,
COCH2, J ) 18.1, 7.2 Hz, 1H), 2.87 (dd, COCH2, J ) 18.1, 5.1
Hz, 1H), 1.95 (m, (CH3)2CH, 1H), 1.68 (m, SiCH, 1H), 0.92 (d,
(CH3)2CH, J ) 6.8 Hz, 3H), 0.86 (d, (CH3)2CH, “partly hidden”,
J ) 6.8 Hz, 3H), 0.86 (s, t-Bu, 9H), 0.38, 0.37 (2s, Si(CH3)2,
3H each); 13C NMR δ 173.9, 154.7, 139.3, 134.0 (2C), 128.8,
127.7 (2C), 65.2, 61.2, 35.7, 32.9, 29.0, 27.7, 25.7 (3C), 22.8,
21.4, -2.1, -2.9; FTIR (film, cm-1) 1781, 1705; MS m/z 375
(M+, 2%), 360 (M - CH3, 40%), 332 (M - C3H7, 100%), 279
(80%), 135 (PhMe2Si, 50%); HRMS (EI, DCI/NH3) calcd for
[C21H34NO3Si]+ (MH+) 376.2308, found 376.2318.
1
dr) yield of 10 as a white solid; mp 77-78 °C. H NMR (500
MHz, CDCl3) δ 4.46 (dd, NCH, J ) 7.6, 1.6 Hz, 1H), 4.31 (dd,
OCH2, J ) 9.3, 1.6 Hz, 1H), 4.26 (dd, OCH2, J ) 9.3, 7.6 Hz,
1H), 3.82 (m, CHOH, 1H), 3.15 (dd, COCH2, J ) 16,7 9.9 Hz,
1H), 3.03 (dd, COCH2, J ) 16.7, 2.6 Hz, 1H), 2.91 (br d, CHOH,
J ) 4.6 Hz, 1H), 1.77 (m, (CH3)2CH, 1H), 0.99, 0.97 (2d,
(CH3)2CH, J ) 6.7 Hz, 3H each), 0.95 (s, t-Bu, 9H); 13C NMR
δ 173.2, 154.9, 72.9, 65.5, 61.0, 39.8, 35.9, 33.5, 25.7(3C), 18.5,
17.7; FTIR (cm-1) 3543, 1780, 1698. HRMS (DEI) calcd for
[C13H24NO4]+ (MH+) 258.1703, found 258.1705.
N-(3′S-Hydroxybutanoyl)-5S-diphenyl-tert-butylsilyl-
oxymethyl-2-pyrrolidinone (11). 11 was obtained from the
oxidation of silane 8 with Hg(OAc)2 and peracetic acid. The
crude product was purified with flash chromatography (50%
Et2O in pentane, Rf 0.30, major diasteromer) to give a 53%
(75 mg, >99:1 dr) yield of 11 as a clear oil. 1H NMR (500 MHz,
CDCl3) δ 7.65-7.62 (m, Ar-H, 2H), 7.57-7.54 (m, Ar-H, 2H),
7.47-7.38 (m, Ar-H, 6H), 4.46 (m, NCH, 1H), 4.24 (m, HOCH,
1H), 3.98 (dd, OCH2, J ) 10.6, 3.6 Hz, 1H), 3.70 (dd, OCH2, J
) 10.6, 2.2 Hz, 1H), 3.22 (br s, OH, 1H), 3.19 (dd, HOCHCH2,
J ) 17.9, 2.6 Hz, 1H), 2.98-2.88 (m, HOCHCH2 and COCH2-
ring, “partly overlap”, 2H), 2.50 (m, COCH2-ring, 1H), 2.15
(m, CH2-ring, 2H), 1.27 (d, CH3CHOH, J ) 6.5 Hz, 3H), 1.05
(s, Si-t-Bu, 9H); 13C NMR δ 176.5, 173.9, 135.49 (2C), 135.47
(2C), 133.0, 132.5, 130.0, 129.9, 127.9 (2C), 127.8 (2C),
64.5, 64.0, 57.8, 45.5, 33.0, 26.8 (3C), 22.3, 21.2, 19.1; FTIR
(film, cm-1) 3470, 1741, 1690; HRMS (EI, DCI/NH3) calcd for
[C25H34NO4Si]+ (MH+) 440.2257, found 440.2242.
N-(3′S-Dimethylphenylsilylbutanoyl)-5S-trityloxy-
methyl-2-pyrrolidinone (7).13,15c 7 was obtained from a
reaction between substrate 317b,22j and Li[Me2PhSiCuI] in THF.
The crude product was purified with flash chromatography
(30% Et2O in pentane, Rf 0.60) to give a 92% (255 mg, 96:4 dr)
1
yield of 7 as a clear oil. H NMR (500 MHz, CDCl3) δ 7.59-
7.56 (m, Ar-H, 2H), 7.40-7.10 (m, Ar-H, 18H), 4.49-4.45 (br
m, NCH, 1H), 3.50 (dd, OCH2, J ) 9.8, 4.0 Hz, 1H), 3.20 (dd,
OCH2, J ) 9.8, 2.7 Hz, 1H), 2.98 (dd, SiCHCH2, J ) 16.2, 3.3
Hz, 1H), 2.95-2.85 (m, COCH2-ring, 1H), 2.78 (dd, SiCHCH2,
J ) 16.2, 11.3 Hz, 1H), 2.47 (ddd, COCH2-ring, J ) 17.8, 9.9,
1.8 Hz, 1H), 2.12-1.92 (2m, CH2-ring, 1H each), 1.59-1.51
(m, SiCH, 1H), 0.94 (d, CH3CHSi, J ) 7.3 Hz, 3H), 0.36, 0.35
(2s, Si(CH3)2, 3H each); 13C NMR δ 176.1, 173.9, 143.6, 137.8,
134.0, 128.6, 127.94, 127.86, 127.75, 127.1, 87.0, 64.1, 56.6,
39.0, 33.2, 21.2, 15.3, 14.4, -4.9, -5.1; FTIR (film, cm-1) 1735,
1697; MS m/z 597 (M + Cl-, 30%), 601 (M + K+, 15%). HRMS
or EA missing.
N-(3′S-Dimethylphenylsilylbutanoyl)-4R-phenyl-1,3-
oxazolidin-2-one (18).13 18 was obtained from a reaction
between substrate 1217a,22j and Li[Me2PhSiCuI] in THF. The
crude product was purified with flash chromatography (30%
N-(3′S-Dimethylphenylsilylbutanoyl)-5S-diphenyl-tert-
butylsilyloxymethyl-2-pyrrolidinone (8). 8 was obtained
from a reaction between substrate 4 and Li[Me2PhSiCuI] in
THF. The crude product was purified with flash chromatog-
raphy (15% Et2O in pentane, Rf 0.40) to give a 93% (255 mg,
(41) Karlsson, S.; Han, F.; Ho¨gberg, H.-E.; Caldirola, P. Tetrahedron:
Asymmetry 1999, 10, 2605-2616.
(42) Ager, D.; Fleming, I. J. Chem. Soc., Chem. Commun. 1978, 177-
178.
1
95:5 dr) yield of 8 as a clear oil. H NMR (500 MHz, CDCl3)
δ 7.62-7.50 (2m, Ar-H, 6H), 7.44-7.40 (3m, Ar-H, 9H), 4.40
(m, NCH, 1H), 3.89 (dd, OCH2, J ) 10.6, 3.7 Hz, 1H), 3.67
(dd, OCH2, J ) 10.6, 2.4 Hz, 1H), 3.00 (dd, SiCHCH2, J ) 16.0,
3.4 Hz, 1H), 2.84 (ddd, COCH2-ring, J ) 17.7, 10.7, 10.3 Hz,
1H), 2.69 (dd, SiCHCH2, J ) 16.0, 11.3 Hz, 1H), 2.44 (ddd,
COCH2-ring, J ) 17.7, 9.2, 3.0 Hz, 1H), 2.05 (m, CH2-ring, 2H),
1.52 (m, SiCH, 1H), 1.02 (s, Si-t-Bu, 9H), 0.90 (d, CH3CHSi, J
) 7.3 Hz, 3H), 0.32, 0.31 (2s, Si(CH3)2, 3H each); 13C NMR δ
(43) Fleming, I.; Newton, T. W. J. Chem. Soc., Perkin Trans. 1 1984,
1805-1808.
(44) Compound 32 was obtained in 58% yield in
a Horner-
Wadsworth-Emmons reaction between TMS-acetaldehyde and meth-
yl diethylphosphonoacetate, using BuLi in Et2O.
(45) Engel, W.; Fleming, I.; Smithers, R. H. J. Chem. Soc., Perkin
Trans. 1 1986, 1637-1641.
(46) Fukuzawa, S.-I.; Matsuzawa, H.; Yoshimitsu, S.-I. J. Org.
Chem. 2000, 65, 1702-1706.
J. Org. Chem, Vol. 70, No. 2, 2005 587

Dambacher and Bergdahl
Et2O in pentane, Rf 0.40) to give a 99% (179 mg, 97:3 dr) yield
of 18 as a white solid; mp 73-75 °C. 1H NMR (500 MHz,
CDCl3) δ 7.48 (m, Ar-H, 2H), 7.36-7.25 (m, Ar-H, 8H), 5.35
(dd, NCH, J ) 8.7, 3.7 Hz, 1H), 4.63 (dd, OCH2, J ) 8.9, 8.7
Hz, 1H), 4.24 (dd, OCH2, J ) 8.9, 3.7 Hz, 1H), 3.00 (dd, COCH2,
J ) 15.8, 3.7 Hz, 1H), 2.68 (dd, COCH2, J ) 15.8, 11.2 Hz,
1H), 1.50 (m, SiCH, 1H), 0.82 (d, CH3CH, J ) 7.3 Hz, 3H),
0.27, 0.26 (2s, SiCH3, 3H each); 13C NMR δ 173.5, 153.6, 139.5,
137.5, 134.2, 129.3, 129.2, 128.9, 127.9, 126.2, 70.1, 57.8, 38.1,
15.8, 14.4, -4.87, -4.89; FTIR (cm-1) 1785, 1703; MS m/z 403
(M + Cl-, 10%), 406 (M + K+, 50%).
N-(3′R-Dimethylphenylsilylbutanoyl)-4S-phenylmeth-
yl-1,3-oxazolidin-2-one (19). 19 was obtained from a reaction
between substrate 1322j,39 and Li[Me2PhSiCuI] in THF. The
crude product was purified with flash chromatography (15%
Et2O in pentane, Rf 0.40) to give a 96% (178 mg, 9:1 dr) yield
of 19 as a white solid; mp 87-90 °C. 1H NMR (500 MHz,
CDCl3) δ 7.53 (m, Ar-H, 2H), 7.38-7.23 (m, Ar-H, 6H), 7.18
(m, Ar-H, 2H), 4.58 (m, NCH, 1H), 4.12 (m, OCH2, 2H), 3.25
(dd, PhCH2, J ) 13.3, 3.4 Hz, 1H), 3.03 (dd, COCH2, J ) 16.1,
3.8 Hz, 1H), 2.74 (dd, COCH2, J ) 16.1, 10.8 Hz, 1H), 2.66
(dd, PhCH2, J ) 13.3, 9.8 Hz, 1H), 1.60 (m, SiCH, 1H), 1.00
(d, CH3CH, J ) 7.3 Hz, 3H), 0.34, 0.33 (2s, Si(CH3)2, 3H each);
13C NMR δ 173.5, 153.6, 137.7, 135.6, 134.2, 129.6, 129.3,
129.1, 128.0, 127.5, 66.4, 55.4, 38.2, 38.1, 15.8, 14.8, -4.7, -4.9;
FTIR (cm-1) 1790, 1697; MS m/z 417 (M + Cl-, 70%), 421 (M
+ K+, 40%); HRMS (EI) calcd for [C22H27NO3Si] 381.1760,
found 381.1756.
N-(3′R-Dimethyl(phenyl)silylbutanoyl)-4S-tert-butyl-
1,3-oxazolidin-2-one (20). 20 was obtained from a reaction
between substrate 1422f,j and Li[Me2PhSiCuI] in THF. The
crude product was purified with flash chromatography (15%
Et2O in pentane, Rf 0.30) to give a 99% (175 mg, 96:4 dr) yield
of 20 as a clear oil. 1H NMR (500 MHz, CDCl3) δ 7.52 (m,
Ar-H, 2H), 7.35 (m, Ar-H, 3H), 4.39 (dd, NCH, J ) 7.6, 1.6
Hz, 1H), 4.24 (dd, OCH2, J ) 9.2, 1.6 Hz, 1H), 4.16 (dd, OCH2,
J ) 9.2, 7.6 Hz, 1H), 3.02 (dd, COCH2, J ) 15.8, 3.2 Hz, 1H),
2.69 (dd, COCH2, J ) 15.8, 11.3 Hz, 1H), 1.57 (m, SiCH, 1H),
0.97 (d, CH3CH, J ) 7.5 Hz, 3H), 0.90 (s, t-Bu, 9H), 0.33, 0.32
(2s, Si(CH3)2, 3H each); 13C NMR δ 173.5, 154.7, 137.5, 134.0,
129.0, 127.8, 65.3, 61.0, 37.6, 35.7, 25.7, 16.1, 14.4, -4.9, -5.1;
FTIR (cm-1) 1782, 1703; MS m/z 387 (M + K+, 40%); HRMS
(EI, DCI/NH3) calcd for [C19H30NO3Si]+ (MH+) 348.1995, found
348.1985.
Hz, 1H), 0.72 (s, t-Bu, 9H), 0.30, 0.24 (2s, Si(CH3)2, 3H each);
13C NMR δ 173.0, 155.0, 141.6, 136.7, 134.4, 129.5, 128.3,
128.1, 128.0, 125.2, 65.5, 61.2, 35.75, 35.70, 32.7, 25.6, -4.0,
-5.0; FTIR (film, cm-1) 1774, 1701; MS m/z 445.2 (M + Cl-,
5%), 448.8 (M + K+, 10%).
N-(3′R-Dimethylphenylsilylbutanoyl)-(4S,5R)-indano-
[1,2-d]oxazolidin-2-one (23). 23 was obtained from a reaction
between substrate 1732 and Li[Me2PhSiCuI] in THF. The crude
product was purified with flash chromatography (30% Et2O
in pentane, Rf 0.40) to give a 93% (166 mg, 4:1 dr) yield of 23
as a clear oil. 1H NMR (500 MHz, CDCl3) δ 7.62 (d, Ar-H, J )
7.7 Hz, 1H), 7.53 (m, Ar-H, 2H), 7.35 (m, Ar-H, 4H), 7.27 (m,
Ar-H, 2H), 5.88 (d, NCH, J ) 7.0 Hz, 1H), 5.24 (m, OCH, 1H),
3.37 (m, Ar-CH2, 2H), 3.03 (dd, NCOCH2, J ) 15.9, 3.8 Hz,
1H), 2.72 (dd, NCOCH2, J ) 15.9, 11.1 Hz, 1H), 1.58 (m, SiCH,
1H), 0.99 (d, CHCH3, J ) 7.4 Hz, 3H), 0.33, 0.32 (2s, Si(CH3)2,
3H each); 13C NMR δ 174.0, 153.1, 139.7, 139.5, 137.7, 134.3
(2C), 130.0, 129.3, 128.3, 128.0 (2C), 127.5, 125.4, 78.2, 63.2,
38.3, 38.0, 15.9, 14.6, -4.82, -4.83; FTIR (film, cm-1) 1770,
1701; HRMS (EI) calcd for [C22H25NO3Si] 379.1604, found
379.1590.
3-(Dimethylphenylsilyl)-3-phenylpropanal (24).13,42 24
was obtained from the reaction of trans-3-phenylpropenal with
Li[Me2PhSiCuI] in THF as solvent. The crude product was
purified with flash chromatography (5% ether in pentane; Rf
0.30) to give a 71% (94 mg) yield of 24 as a clear oil. 1H NMR
(500 MHz, CDCl3) δ 9.55 (dd, CHO, J ) 2.4, 1.5 Hz, 1H), 7.42-
7.29 (m, Ar-H, 5H), 7.24-7.19 (m, Ar-H, 2H), 7.14-7.09 (m,
Ar-H, 1H), 6.98-6.94 (m, Ar-H, 2H), 2.92-2.84 (m, R-CH2, 2H),
2.68-2.60 (m, CHSi, 1H), 0.28, 0.25 (2s, Si(CH3)2, 3H each);
13C NMR (125 MHz, CDCl3) δ 202.7, 141.4, 136.4, 134.3 (2C),
129.7, 128.5 (2C), 128.1 (2C), 127.9 (2C), 125.4, 43.8, 30.3, -4.0,
-5.3; FTIR (film, cm-1) 2956, 1721, 1251, 700; MS m/z 267
(M+ - H, 4%), 253 (M n -CH3, 10%), 190 (M - H, C6H6, 52%),
175 (M - C7H9, 30%), 135 (M - C9H9O).
3-(Dimethylphenylsilyl)butanal (25).2c,13 25 was obtained
from the reaction of trans-propenal with Li[Me2PhSiCuI] in
THF as solvent. The crude product was purified with flash
chromatography (5% ether in pentane; Rf 0.30) to give a 82%
1
(82 mg) yield of 25 as a clear oil. H NMR (500 MHz, CDCl3)
δ 9.68 (dd, CHO, J ) 3.2, 1.2 Hz, 1H), 7.52-7.49 (m, Ar-H,
2H), 7.40-7.35 (m, Ar-H, 3H), 2.44 (ddd, R-CH2, J ) 16.4, 3.7,
1.2 Hz, 1H), 2.16 (ddd, R-CH2, J ) 16.4, 10.9, 3.2 Hz, 1H), 1.51
(m, CHSi, 1H), 1.00 (d, CH3, J ) 7.3 Hz, 3H), 0.32, 0.31 (2s,
Si(CH3)2, 3H each); 13C NMR (125 MHz, CDCl3) δ 203.4, 137.3,
134.1 (2C), 129.5, 128.1 (2C), 46.2, 14.8, 14.1, -4.7, -5.2; FTIR
(film, cm-1) 3070, 2957, 1708, 1427, 1251, 701; MS m/z 191
(M+ - CH3,70%) 135 (M - C4H7O, 100%).
N-(3′R-Dimethylphenylsilylheptanoyl)-4S-tert-butyl-
1,3-oxazolidin-2-one (21). 21 was obtained from a reaction
between substrate 1522j and Li[Me2PhSiCuI] in THF. The
crude product was purified with flash chromatography (15%
Et2O in pentane, Rf 0.30) to give a 99% (192 mg, 98:2 dr) yield
3-(Dimethylphenylsilyl)-2-methylpropionamide (26).13
26 was obtained from the reaction of 2-methylacrylamide with
Li[Me2PhSiCuI] in THF as solvent. The crude product was
purified with flash chromatography (100% ether; Rf 0.20) to
give a 60% (63 mg) yield of 26 as a white solid; mp 58-60 °C.
1H NMR (500 MHz, CDCl3) δ 7.55-7.50 (m, Ar-H, 2H), 7.38-
7.35 (m, Ar-H, 3H), 5.60, 5.32 (2br s, NH2, each 1H), 2.33 (m,
CH, 1H), 1.26 (dd, CH2, J ) 14.7, 6.5 Hz, 1H), 1.15 (d, CH3, J
) 6.9 Hz, 3H), 0.94 (dd, CH2, J ) 14.7, 7.8 Hz, 1H), 0.34, 0.32
(2s, Si(CH3)2, 3H each); 13C NMR (125 MHz, CDCl3) δ 180.2,
139.0, 133.8 (2C), 129.3, 128.1 (2C), 37.0, 21.4, 21.3, -2.0, -2.4;
FTIR (cm-1) 3192, 2961, 1647, 1250, 800; MS m/z 221 (M+,
3%), 220, (M - H, 16%), 205 (M - NH2), 177 (M - CONH2,
22%). Anal. Calcd for C12H19NOSi: C, 65.11; H, 8.55; N, 6.33.
Found: C, 64.81; H, 8.68; N, 6.10.
3-(Dimethylphenylsilyl)butanoic Acid Ethyl Ester
(27).13,42 27 was obtained from the reaction of trans-butenoic
acid ethyl ester with Li[Me2PhSiCuI] in THF as solvent. The
crude product was purified with flash chromatography (5%
ether in pentane; Rf 0.35) to give a 95% (128 mg) yield of 27
as a clear oil. 1H NMR (500 MHz, CDCl3) δ 7.53-7.49 (m,
Ar-H, 2H), 7.39-7.34 (m, Ar-H, 3H), 4.09 (q, OCH2CH3, J )
7.2 Hz, 2H), 2.39 (dd, R-CH2, J ) 15.1, 4.0 Hz, 1H), 2.06 (dd,
R-CH2, J ) 15.1, 11.2 Hz, 1H), 1.46 (m, CHSi, 1H), 1.24 (t,
1
of 21 as a clear oil. H NMR (500 MHz, CDCl3) δ 7.54-7.52
(m, Ar-H, 2H), 7.35-7.33 (m, Ar-H, 3H), 4.35 (dd, NCH, J )
7.7, 1.2 Hz 1H), 4.22 (dd, OCH2, J ) 9.1, 1.2 Hz, 1H), 4.12
(dd, OCH2, J ) 9.1, 7.7 Hz, 1H), 2.94 (m, COCH2, 2H), 1.58
(m, SiCH, 1H), 1.48 (m, CH2, 1H), 1.29 (m, CH2, 1H), 1.22-
1.12 (m, 2 × CH2, 4H), 0.87 (s, t-Bu, 9H), 0.80 (t, CH3CH2, J
) 6.9 Hz, 3H), 0.33, 0.32 (2s, Si(CH3)2, 3H each); 13C NMR δ
173.9, 154.9, 138.6, 134.2, 129.1, 128.0, 65.5, 61.3, 36.2,
35.9, 31.5, 30.3, 25.9, 23.1, 21.0, 14.1, -3.6, -3.8; FTIR (film,
cm-1) 1782, 1705; MS m/z 428.5 (M + K+, 30%); HRMS (EI,
DCI/NH3) calcd for [C22H39N2O3Si]+ (M + H4N+) 407.2730,
found 407.2745.
N-(3′S-Dimethylphenylsilyl-3′-phenylpropanoyl)-4S-
tert-butyl-1,3-oxazolidin-2-one (22). 22 was obtained from
a reaction between substrate 1641 and Li[Me2PhSiCuI] in THF.
The crude product was purified with flash chromatography
(30% Et2O in pentane, Rf 0.40) to give a 99% (200 mg, 97:3 dr)
1
yield of 22 as a clear oil. H NMR (500 MHz, CDCl3) δ 7.42-
7.30 (m, Ar-H, 5H), 7.15 (m, Ar-H, 2H), 7.05 (m, Ar-H, 1H),
6.94 (m, Ar-H, 2H), 4.18 (dd, NCH, J ) 7.8, 1.6 Hz, 1H), 4.14
(dd, OCH2, J ) 9.2, 1.6 Hz, 1H), 3.97 (dd, OCH2, J ) 9.2, 7.8
Hz, 1H), 3.58 (dd, PhCH, J ) 16.1, 12.2 Hz, 1H), 3.09 (dd,
COCH2, J ) 16.1, 3.6 Hz, 1H), 3.05 (dd, COCH2, J ) 12.2, 3.6
588 J. Org. Chem., Vol. 70, No. 2, 2005

Conjugate Additions of a Simple Monosilylcopper Reagent
OCH2CH3, J ) 7.2 Hz, 3H), 0.99 (d, CHCH3, J ) 7.3 Hz, 3H),
0.30 (s, Si(CH3)2, 6H); 13C NMR (125 MHz, CDCl3) δ 174.1,
137.6, 134.2 (2C), 129.3, 128.0 (2C), 60.4, 37.1, 16.7, 14.7, 14.5,
-4.8, -5.1; FTIR (film, cm-1) 2956, 1732, 1251, 701; MS m/z
250 (M+, 7%), 235 (M - CH3, 57%), 205 (M - OCH2CH3, 100%),
173 (M - C6H5, 65%), 135 (M - C6H11O2, 50%), 105 (12%), 75
(26%).
was purified with flash chromatography (2% ether in pentane;
1
Rf 0.30) to give a 78% (122 mg) yield of 33 as a clear oil. H
NMR (500 MHz, CDCl3) δ 7.57-7.54 (m, Ar-H, 2H), 7.41-7.31
(m, Ar-H, 3H), 3.62 (s, OCH3, 3H), 2.46-2.29 (m, COCH2 and
SiCH, “partly overlap”, 3H), 0.41, 0.40 (2s, Si(CH3)2, 3H each),
0.12 (s, Si(CH3)3, 9H); 13C NMR (125 MHz, CDCl3) δ 172.8,
135.7, 134.1, 129.6, 127.8, 107.4, 86.0, 51.6, 34.7, 17.7, 0.19,
-4.5, -5.4; FTIR (film, cm-1) 2957, 2160, 1743, 1250, 842;
HRMS (EI) calcd for [C17H26O2Si2] 318.1471, found 318.1477.
3-(Dimethylphenylsilyl)cyclopentanone (34).13,45 34
was obtained from the reaction of 2-cyclopenten-1-one with
Li[Me2PhSiCuI] in THF as solvent. The crude product was
purified with flash chromatography (30% ether in pentane; Rf
0.50) to give a 99% (106 mg) yield of 34 as a clear oil. 1H NMR
(500 MHz, CDCl3) δ 7.53-7.50 (m, Ar-H, 2H), 7.41-7.35 (m,
Ar-H, 3H), 2.32-2.19 (m, CH2, 2H), 2.17-2.06 (m, CH2, 2H),
1.91 (dd, CH2, J ) 18.1, 13.1 Hz, 1H), 1.75-1.62 (m, CH2, 1H),
1.61-1.51 (m, CHSi, 1H), 0.34 (s, Si(CH3)2, 6H); 13C NMR (125
MHz, CDCl3) δ 221.0, 137.2, 134.0(2C), 129.5, 128.1(2C), 40.3,
39.5, 25.2, 24.2, -4.7, -4.8; FTIR (film, cm-1) 3458, 3069, 2957,
1736, 1251, 700; MS m/z 217 (M+ - H, 5%), 203 (M - CH3,
2%), 135 (M - C5H7O, 30%), 67 (C5H7, 100%).
3-(Methyldiphenylsilyl)butanoic Acid Ethyl Ester (28).
28 was obtained from the reaction of trans-butenoic acid ethyl
ester with Li[MePh2SiCuI] in dimethyl sulfide as solvent. The
crude product was purified with flash chromatograpy (5% ether
in pentane; Rf 0.30) to give a 70% (98 mg) yield of 28 as a
1
clear oil. H NMR (500 MHz, CDCl3) δ 7.58-7.54 (m, Ar-H,
4H), 7.43-7.35 (m, Ar-H, 6H), 4.09 (q, OCH2CH3, J ) 7.2 Hz,
2H), 2.49 (dd, R-CH2, J ) 15.3, 3.4 Hz, 1H), 2.12 (dd, R-CH2C,
J ) 15.3, 11.6 Hz, 1H), 1.93 (m, CHSi, 1H), 1.24 (t, OCH2CH3,
J ) 7.2 Hz, 3H), 1.06 (d, CH3CHSi, J ) 7.3 Hz, 3H), 0.58 (s,
SiCH3, 3H); 13C NMR (125 MHz, CDCl3) δ 174.0, 135.7, 135.6,
135.04 (2C), 135.02 (2C), 129.59, 129.56, 128.13 (2C), 128.12
(2C), 60.5, 37.2, 15.3, 14.9, 14.5, -6.3; FTIR (film, cm-1) 3069,
2957, 1733, 1428, 1254, 1210, 1110, 700; MS m/z 312 (M+, 3%),
297 (M - CH3, 11%), 267 (M - C2H5O, 18%), 236 (M - C6H6,
100%), 197 (Ph2MeSi, 12%); HRMS (EI, DCI/NH3) calcd for
[C19H28NO2Si]+ (M + H4N+) 330.1889, found 330.1893.
3-(Dimethylphenylsilyl)-3-methylcyclopentanone (35).42
35 was obtained from the reaction of 3-methyl-2-cyclopenten-
1-one with Li[Me2PhSiCuI] in dimethyl sulfide as solvent. The
crude product was purified with flash chromatography (15%
ether in pentane; Rf 0.40) to give a 85% (97 mg) yield of 35 as
a clear oil. 1H NMR (500 MHz, CDCl3) δ 7.53-7.50 (m,
Ar-H, 2H), 7.41-7.35 (m, Ar-H, 3H), 2.32-2.18 (2m, CH2, each
1H), 2.11-1.98 (m, CH2, 2H), 1.90 (d, CH2, J ) 18.0 Hz, 1H),
1.72-1.65 (m, CH2, 1H), 1.04 (s, CCH3, 3H), 0.36, 0.35 (2s,
Si(CH3)2, 3H each); 13C NMR (125 MHz, CDCl3) δ 220.8, 136.3,
134.3 (2C), 129.4, 127.9 (2C), 48.3, 35.2, 31.1, 25.6, 22.1, -5.99,
-6.05; FTIR (film, cm-1) 2955, 1740, 1427, 1251, 854, 702; MS
m/z 232 (M+, 2%), 231 (M - H, 12%), 217 (M - CH3, 30%),
154 (M - C6H6, 12%), 135 (M - C6H9O, 30%), 83 (C6H11, 50%).
3-(Dimethylphenylsilyl)-3-methylcyclohexanone (36).42
36 was obtained from the reaction of 3-methyl-2-cyclohexen-
1-one with Li[Me2PhSiCuI] in dimethyl sulfide as solvent. The
crude product was purified with flash chromatography (15%
ether in pentane; Rf 0.40) to give a 88% (106 mg) yield of 36
as a clear oil. 1H NMR (500 MHz, CDCl3) δ 7.52-7.48 (m,
Ar-H, 2H), 7.42-7.35 (m, Ar-H, 3H), 2.36 (d, R-CH2, J ) 13.4
Hz, 1H), 2.31-2.25 (2m, R′-CH2, 1H), 2.24-2.16 (ddd, R′-CH2,
J ) 13.9, 7.0, 1.0 Hz, 1H), 2.01-1.89 (2m, partly hidden, CH2,
2H), 2.00 (d, partly hidden, R-CH2, J ) 13.4 Hz, 1H), 1.76 (ddd,
CH2, J ) 13.5, 12.3, 4.4 Hz, 1H), 1.52 (2m, CH2, 1H), 0.94 (s,
CCH3, 3H), 0.33 (2s, Si(CH3)2, 6H); 13C NMR (125 MHz, CDCl3)
δ 213.3, 136.1, 134.8 (2C), 129.5, 128.0 (2C), 48.5, 41.8, 31.0,
26.5, 23.1, 19.1, -6.36, -6.43; FTIR (film, cm-1) 2954, 1709,
1427, 1252, 816, 703; MS m/z 246 (M+, 2%), 245 (M - H, 10%),
231 (M - CH3, 100%), 135 (M - C7H10O, 85%), 95 (C7H11, 50%).
3-(Dimethylphenylsilyl)-3-phenylpropanoic Acid Meth-
yl Ester (29).13,43 29 was obtained from the reaction of trans-
3-phenylpropenoic acid methyl ester with Li[Me2PhSiCuI] in
THF as solvent. The crude product was purified with flash
chromatography (10% ether in pentane; Rf 0.60) to give a 91%
(133 mg) yield of 29 as a clear oil. 1H NMR (500 MHz, CDCl3)
δ 7.45-7.33 (m, Ar-H, 5H), 7.24-7.19 (m, Ar-H, 2H), 7.14-
7.09 (m, Ar-H, 1H), 7.00-6.95 (m, Ar-H, 2H), 3.49 (s, OCH3,
3H), 2.88 (dd, CHSi, J ) 11.1, 4.9 Hz, 1H), 2.78 (dd, R-CH2, J
) 15.8, 11.1 Hz, 1H), 2.67 (dd, R-CH2, J ) 15.8, 4.9 Hz, 1H),
0.28, 0.24 (2s, Si(CH3)2, 3H each); 13C NMR (125 MHz, CDCl3)
δ 173.6, 142.0, 136.7, 134.3 (2C), 129.5, 128.3 (2C), 127.9 (2C),
127.7 (2C), 125.2, 51.6, 35.0, 32.5, -3.9, -5.3; FTIR (film, cm-1
)
3024, 2953, 1732, 1252, 835; MS m/z 298 (M+, 78%), 283 (M -
CH3, 20%), 267 (M - OCH3, 58%), 222 (18%), 208 (38%), 193
(39%), 135 (M - C10H11O2, 87%), 104 (100%).
4-(Methyldiphenylsilyl)-4-phenyl-butan-2-one (30). 30
was obtained from the reaction of 4-phenyl-3-buten-2-one with
Li[MePh2SiCuI] in THF as solvent. The crude product was
purified with flash chromatography (15% ether in pentane; Rf
0.40) to give an 85% (125 mg) yield of 30 as a clear oil. 1H
NMR (500 MHz, CDCl3) δ 7.55-6.90 (m, Ar-H, 15H), 3.37 (dd,
CHSi, J ) 11.4, 3.6 Hz, 1H), 2.99 (dd, R-CH2, J ) 16.9, 11.4
Hz, 1H), 2.77 (dd, R-CH2, J ) 16.9, 3.6 Hz, 1H), 1.95 (s, CH3,
3H), 0.46 (s, SiCH3, 3H); 13C NMR (125 MHz, CDCl3) δ 208.0,
141.7, 135.5 (2C), 135.3, 135.1 (2C), 134.7, 129.8, 129.6, 128.34
(2C), 128.32 (2C), 128.1 (2C), 128.0 (2C), 125.3, 44.7, 30.4, 30.1,
-5.2; FTIR (film, cm-1) 3069, 3024, 2885, 1717, 1252, 790, 700;
HRMS (EI) calcd for [C23H24OSi] 344.1596, found 344.1608.
4-(Dimethylphenylsilyl)-4-methyl-pentan-2-one (31).42
31 was obtained from the reaction of 4-methyl-3-penten-2-one
with Li[Me2PhSiCuI] in dimethyl sulfide as solvent. The crude
product was purified with flash chromatography (10% ether
in pentane; Rf 0.70) to give a 81% (93 mg) yield of 31 as a
Acknowledgment. Acknowledgment is made to the
Donors of the American Chemical Society Petroleum
Research Fund for support of this research (PRF 41199-
AC1). This work was also funded by San Diego Founda-
tion (Blasker), and the San Diego State University
Foundation. The authors thank Dendreon Pharmaceu-
ticals and Dr. Dave Duncan (Corvas) for a substantial
donation of chemicals. The authors also thank Mr.
Robert Anness and Dr. Frances Separovic for crucial
assistance and Dr. LeRoy Lafferty for NMR support.
1
clear oil. H NMR (500 MHz, CDCl3) δ 7.53-7.49 (m, Ar-H,
2H), 7.40-7.34 (m, Ar-H, 3H), 2.30 (s, CH2CO, 2H), 2.04 (s,
COCH3, 3H), 1.05 (s, (CH3)2C, 6H), 0.33 (s, Si(CH3)2, 6H); 13
C
NMR (125 MHz, CDCl3) δ 209.7, 137.2, 134.8 (2C), 129.2, 127.8
(2C), 51.3, 32.8, 23.5 (2C), 20.5, -5.5 (2C); FTIR (film, cm-1
)
2957, 2862, 1716, 1427, 1357, 1251, 815, 703; MS m/z 234 (M+,
3%), 219 (M - CH3, 100%), 157 (M - C6H5, 30%), 135 (M -
C6H11O, 30%), 83 (C6H11, 50%).
Supporting Information Available: General and chemi-
cal information plus copies of 1H and 13C NMR spectra of
compounds 1-2, 4-11, 18-31, and 33-36. This material is
available free of charge via the Internet at http://pubs.acs.org.
3-(Dimethylphenylsilyl)-5-trimethylsilylpent-4-ynoic
Acid Methyl Ester (33). 33 was obtained from a reaction of
5-trimethylsilyl-pent-2-ene-4-ynoic acid methyl ester (32)44
with Li[Me2PhSiCuI] in DMS as solvent. The crude product
JO048269E
J. Org. Chem, Vol. 70, No. 2, 2005 589