Silyl cuprate couplings: Less silicon, accelerated, yet catalytic in copper [4]

Full text of DOI:10.1021/ja980152i

J. Am. Chem. Soc. 1998, 120, 4021-4022
4021
Silyl Cuprate Couplings: Less Silicon, Accelerated,
Yet Catalytic in Copper
Bruce H. Lipshutz,* Joseph A. Sclafani, and
Toshikatsu Takanami
Figure 1.
Table 1. Reactions of PhMe2SiZnMe2Li + cat Me2Cu(CN)Li2
Department of Chemistry, UniVersity of California
Santa Barbara, California 93106
ReceiVed January 14, 1998
Among the myriad uses of silicon in organic synthesis,1 the
dimethylphenylsilyl moiety occupies a special niche, perhaps most
notably in its service as a hydroxyl group surrogate.2 Introduction
of this moiety is commonly effected via a silyl cuprate reagent,
such as that formed from CuCN and 2 equiv of PhMe2SiLi (i.e.,
“(PhMe2Si)2Cu(CN)Li2”).3 This species, now in its second decade
of usage, requires not only 2 equiv of silyllithium but, more
importantly, stoichiometric amounts of copper which detract from
its appeal, in particular for large-scale reactions. We now report
a solution to these issues which allows for consumption of only
one silyl group, is applicable to highly hindered substrates, and
relies on catalytic amounts of Cu(I). In addition, we disclose
the unprecedented use of a rare earth as a new catalyst for
accelerating 1,4-additions of an in situ derived silylcuprate.
Addition of a toluene solution of Me2Zn to preformed PhMe2-
SiLi in THF at -78 °C generates known PhMe2SiZnMe2Li.4
Introduction of 3 mol % of the higher order cyanocuprate Me2-
Cu(CN)Li2 to this mixed zincate followed by a substrate leads to
high yields of silylated adducts (Figure 1). The presumed reactive
species, mixed cuprate (PhMe2Si)(Me)Cu(CN)Li2 (1, Scheme 1),
generated in situ via a facile, rapid ligand exchange at low
temperatures,5 selectively releases silicon rather than methyl from
copper.6 Representative examples are illustrated in Table 1.
Conjugate additions were studied in highly challenging, â,â-
disubstituted enones including isophorone, verbenone, mesityl
oxide, and an octalone (entries 1-4), with which excellent yields
of â-silylated products were obtained. 1,4-Addition to crotonal-
dehyde and myrtenal were equally successful (entries 5 and 6).
Cuprate alkylations with epoxides also proceeded smoothly to
the 1,2- or 1,4-silyl alcohols (entries 7-9). Poor results with
the corresponding zincates alone4,7 clearly indicated the key role
being played by copper in this chemistry.
a Characterized by spectral and HRMS data. b Same conditions as
used for reactions where 3 mol % cuprate was present. c Isolated,
chromatographically purified materials. d See ref 4. e Not attempted.
f Ratio of isomers is 3:1. g Ratio is 4:1. h E:Z ratio is 1:1.
Scheme 1
* Author to whom correspondence should be addressed at the following:
phone 805-893-2521; fax 805-893-8265; e-mail Lipshutz@chem.ucsb.edu.
(1) Colvin, E. W. Silicon in Organic Synthesis; Butterworths: London,
1981. Weber, W. P. Silicon Reagents for Organic Synthesis; Springer-
Verlag: Berlin, 1983. Colvin, E. W. Silicon Reagents in Organic Synthesis;
Academic Press: Orlando, FL, 1988.
(2) Fleming, I.; Henning, R.; Plaut, H. J. Chem. Soc., Chem. Commun.
1984, 351. Fleming, I.; Sanderson, P. E. J. Tetrahedron Lett. 1987, 28, 4229.
Tamao, K.; Kawachi, A.; Ito, Y. J. Am. Chem. Soc. 1992, 114, 3989.
(3) (a) Fleming, I.; Newton, T. W.; Roessler, F. J. Chem. Soc., Perkin Trans.
1 1981, 2527. (b) Ager, D. J.; Fleming, I.; Patel, S. K. Ibid. 1981, 2520. (c)
Fleming, I.; Thomas, A. P. J. Chem. Soc., Chem. Commun. 1985, 411. (d)
Fleming, I.; Rowley, M.; Cuadrado, P.; Gonzalez-Nogal, A. M.; Pulido, F. J.
Tetrahedron 1989, 45, 413. (e) Barbero, A.; Cuadrado, P.; Fleming, I.;
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Fleming, I. In Organocopper Reagents; Taylor, R. J. K., Ed.; Oxford University
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Trans. 1 1994, 2527. Tuckmantel, W.; Oshima, K.; Nozaki, H. Chem. Ber.
1986, 119, 1581.
(5) For recent examples of this type of ligand exchange, see: Lipshutz, B.
H.; Woo, K.; Gross, T.; Buzard, D. J.; Tirado, R. Synlett 1997, 477. Lipshutz,
B. H.; Wood, M. R.; Tirado, R. J. Am. Chem. Soc. 1995, 117, 6126. Lipshutz,
B. H.; Wood, M. R. Ibid. 1993, 115, 12625. See also: Lipshutz, B. H. In
Organometallics in Synthesis; Schlosser, M., Ed.; Wiley: Chichester. In press.
(6) Fleming, I.; Newton, T. W. J. Chem. Soc., Perkin Trans. 1 1984, 1805.
Lipshutz, B. H.; Reuter, D. C.; Ellsworth, E. L. J. Org. Chem. 1989, 54, 4975.
(7) MacLean, B. L.; Hennigar, K. A.; Kells, K. W.; Singer, R. D.
Tetrahedron Lett. 1997, 38, 7313.
Initial cuprate couplings with R,â-unsaturated carbonyl sub-
strates, which are catalytic in copper, implicate an intermediate
zinc enolate (e.g., 2, Scheme 1),8 which is potentially subject to
further C-C bond constructions. Thus, trapping 2, derived from
(8) Lipshutz, B. H.; Wood, M. R. Tetrahedron Lett. 1994, 35, 6433.
S0002-7863(98)00152-8 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/14/1998

4022 J. Am. Chem. Soc., Vol. 120, No. 16, 1998
Communications to the Editor
Table 2. Effect of Additives on Rates of 1,4-Addition Reactions
of Enones with Silylzincate/3% Cuprate
Scheme 2
Scheme 3
a 5 mol % was used. b 1.2 equiv were used. c The remaining mass
was starting material. d 1,2-Adduct was the major product.
some unattractive features associated with these: both are used
in excess, the former generates a silyl enol ether requiring
subsequent hydrolysis, and the latter is limiting in its functional
group tolerance. To our knowledge, no other additive of any
generality is known in copper chemistry which increases rates of
Michael additions and giVes the carbonyl product directly. We
have found that Yb(OTf)3 and, especially, Sc(OTf)312 significantly
enhance 1,4-additions of silyl cuprates and do so in a catalytic
fashion. Hence, for the case of isophorone (Scheme 3), in the
presence of only 5 mol % Sc(OTf)3, along with 3 mol % cuprate
and the silylzincate, adduct 8 is obtained in 5 min. Similarly,
treatment of both verbenone and mesityl oxide under the influence
of this rare earth derivative reduced reaction times from hours to
5 min (Table 2). Thus, these couplings, which are catalytic in
both copper and Sc(OTf)3, are at least three times faster than the
corresponding reactions done stoichiometrically in cuprate!13
In summary, valuable silylated derivatives can now be realized
using a silylzincate/cyanocuprate transmetalation scheme. Most
notably, the process minimizes the amount of silyl ligand involved
and requires the presence of only small percentages of transition
metal, Cu(I). While efficiencies are high, rates of couplings with
Michael acceptors are slowed. This observation has led to the
unprecedented use of catalytic amounts of Sc(OTf)3 as an additive
for accelerating 1,4-additions of a silyl group via organocopper
reagents. Other uses of rare earth derivatives in cuprate chemistry
are now under active investigation.
ethyl crotonate, with an aldehyde prior to an aqueous workup
afforded the R-alkylated, â-silylated product 3 in good overall
yield. Likewise, copper-catalyzed silylcupration of terminal
alkyne 4 leads to presumed intermediate vinylzincate9 5 (Scheme
2). Subsequent exposure of 5 to cyclohexenone, given the
continuing presence of Cu(I), induces a second-stage Michael
addition ultimately affording the 3-component coupling product
6.
Due to the catalytic nature of this process, as well as the
requirement for only 1 equiv of silyl ligand, reaction rates can
be slowed considerably relative to those expected with stoichio-
metric silyl cuprate 1. That is, several bimolecular events must
occur for a successful catalytic cycle (i.e., cuprate-zincate
transmetalation, 1,4-addition, copper/lithium enolate-zincate
transmetalation). Thus, for example, while disilylcuprate 1 (at
0.07 M) reacts with isophorone 7 in 15 min, this highly diluted
(0.0024 M in cuprate) copper-catalyzed zincate coupling requires
2.5 h under otherwise identical conditions (-78 °C, THF; Scheme
3). In an effort to accelerate this process, we considered the usual
additives Me3SiCl10 and BF3‚OEt2.11 Unfortunately, there are
Acknowledgment. Financial support provided by the National Science
Foundation (CHE 93-03883) is warmly acknowledged.
Supporting Information Available: Experimental details and 1H
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(9) Wakamatsu, K.; Nonaka, T.; Okuda, Y.; Tuckmantel, W.; Oshima, K.;
Utimoto, K.; Nozaki, H. Tetrahedron 1986, 42, 4427.
(10) Corey, E. J.; Boaz, N. W. Tetrahedron Lett. 1985, 26, 6019. Alexakis,
A.; Sedrani, R.; Mangeney, P. Ibid. 1990, 31, 345. Alexakis, A.; Berlan, J.;
Besace, Y. Ibid. 1986, 27, 1047. Johnson, C. R.; Marren, T. J. Ibid. 1987, 28,
27. Hiroguchi, Y.; Komatsu, M.; Kuwajima, I. Tetrahedron Lett. 1989, 30,
7087. Nakamura, E.; Matsuzawa, S.; Horiguchi, Y.; Kuwajima, I. Ibid. 1986,
27, 4025, 4029.
JA980152I
(12) Kobayashi, S. Synlett 1994, 689. Ishihara, K.; Karumi, Y.; Yamamoto,
H. Synlett 1996, 839.
(13) Thus, the Sc(OTf)3 more than makes up for the fact that the cuprate
is ca. 30 times less concentrated when used catalytically in these couplings
(i.e., compare concentrations of Cu(I) in Scheme 3, last two reactions).
(11) Lipshutz, B. H.; Ellsworth, E. L.; Siahaan, T. J. J. Am. Chem. Soc.
1989, 111, 1351. Yamamoto, Y. Angew. Chem., Int. Ed. Engl. 1986, 25, 947.
Lipshutz, B. H.; Parker, D. A.; Kozlowski, J. A.; Nguyen, S. L. Tetrahedron
Lett. 1984, 25, 5959. Smith, A. B.; Jerris, P. J. J. Org. Chem. 1982, 47, 1845.