Employing the simple monosilylcopper reagent, Li[PhMe2SiCuI], in 1,4-addition reactions

Article abstract of DOI:10.1039/b210792a

Conjugate addition reactions using the simple Li[PhMe₂SiCuI] reagent to a variety of α,β-unsaturated carbonyl compounds is described; dimethyl sulfide from the purification of CuI plays a key role for very high yields as well as high stereosele

Full text of DOI:10.1039/b210792a

Employing the simple monosilylcopper reagent, Li[PhMe2SiCuI], in
1,4-addition reactions†
Jesse Dambacher and Mikael Bergdahl*
Department of Chemistry, San Diego State University, San Diego, CA 92182-1030, USA.
E-mail: bergdahl@sciences.sdsu.edu
Received (in Corvallis, OR, USA) 30th October 2002, Accepted 19th November 2002
First published as an Advance Article on the web 3rd December 2002
Conjugate addition reactions using the simple Li[PhMe2Si-
CuI] reagent to a variety of a,b-unsaturated carbonyl
compounds is described; dimethyl sulfide from the purifica-
tion of CuI plays a key role for very high yields as well as
high stereoselectivities in the formation of b-silyl carbonyl
compounds.
the simple monosilylcopper reagent are superior to those from
other known silylcopper classes on the same substrates,13 not
only with respect to chemical yield, but also levels of
stereoselectivity. High chemical yields (71–99%) using a,b-
unsaturated ketones, aldehydes, and esters, suggests that there is
little, if any, oligomerization. We found the monosilylcopper
reagent obtained from CuI/DMS undergoes efficient conjugate
additions to moderately unreactive a,b-unsaturated substrates
with imides as well as esters, where excellent isolated yields
( > 90%) were obtained (entries 5 and 6). Remarkably, Li[Ph-
Me2SiCuI] also underwent a conjugate addition with an a,b-
unsaturated amide in 60% yield (entry 9), showing that it is
possible to conduct a conjugate addition in the presence of fairly
acidic protons. A significant advantage in terms of cost and
reducing chemical waste is that preparing Li[PhMe2SiCuI]
requires only one equivalent of PhMe2SiLi, whereas other
commonly used silyl copper reagents, e.g. Li[(PhMe2Si)2Cu]-
LiCN, require two equivalents of PhMe2SiLi per CuCN.
The Li[PhMe2SiCuI] reagent was scrutinized in asymmetric
conjugate additions to some optically active a,b-unsaturated
Carbon–silicon bonds have fundamental roles in organic
synthesis, for example as control moieties for stereochemistry
in chemical reactions,1 or as precursors to introduce a hydroxy
function.2 Among the silyl substituted variants available, the
dimethylphenylsilyl group is very useful because it can be
removed under oxidative conditions (Tamao–Fleming)3,2b to
make alcohols via retention of stereochemistry.2a Hence,
establishing the carbon–silicon bond configuration in the b-
position to a carbonyl group serves as a complementary way of
making enantiomerically pure aldol fragments. The most
frequent way of introducing a PhMe2Si group to a b-carbonyl
carbon is via the conjugate addition of a silylcuprate reagent to
an a,b-unsaturated carbonyl compound.4b,5
Much attention has been focused on the silylcyanocuprates,
depicted as (PhMe2Si)2Cu(CN)Li2,6a or Li[(PhMe2Si)2Cu]-
LiCN,6b as PhMe2Si donors over the last two decades,4a yet it is
rather surprising that little consideration has been paid to the
simpler Li[PhMe2SiCuI]7 reagent in conjugate addition reac-
tions. We now report that the Li[PhMe2SiCuI] reagent works
extraordinarily well, which counters previous indications.8 The
monosilylcopper reagent is more useful than expected for
1,4-type additions (Scheme 1).
Table 1 Reactions of Li[PhMe2SiCuI]
Entry Substrate
1
Producta
Yield (%)b
82c
We have obtained high yields of products in the conjugate
addition process employing the simple monosilylcopper reagent
even without external additives, such as tributylphosphine,8b
HMPA,8a or dialkylzinc.9 In THF at 278 °C, Li[PhMe2SiCuI]
was prepared from 1 equiv of LiSiMe2Ph and 1 equiv10 of CuI,
purified via its dimethyl sulfide complex.11 The corresponding
a,b-unsaturated substrate was added at 278 °C, and the
reaction temperature was increased toward 0 °C over a period of
5–8 h depending on the reactivity of the starting material.
Representative results are shown in Table 1.12
2
71c
3
4
95c
91c
The Li[PhMe2SiCuI] reagent seems mild enough to work in
the presence of fairly sensitive substrates, and slow enough to
prompt diastereoselective additions. Our results obtained with
5
99c
Ratiod
6
7
8
92c 96+4
63e 1+1 (2DMS)
76e 85+15 (+DMS)f
9
60c
Scheme 1
a Characterized by NMR (1H and 13C), IR and MS. b Isolated and purified.
c Reactions were conducted using a CuI·0.75DMS complex. d Ratio of
diastereomers. e 99.999% reagent purity CuI (Aldrich). f 0.75 equivalents of
DMS vs. CuI.
† Electronic supplementary information (ESI) available: Typical experi-
mental procedure, 1H-NMR, 13C-NMR, MS and IR spectral data for all b-
silyl carbonyl compounds (PDF). See http://www.rsc.org/suppdata/cc/b2/
b210792a/
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This journal is © The Royal Society of Chemistry 2003

substrates, (entries 5–8). In entry 5,14 not only is the chemical
yield almost quantitative but also de is 94% for the conjugate
addition of the monosilylcopper reagent. This result is some-
what surprising since tributylphosphine was reported ‘im-
perative’ for the Li[PhMe2SiCuI] reagent to undergo a con-
jugate addition to an imide, even at 0 °C.8b Likewise, the
Li[(PhMe2Si)2Cu]LiCN reagent typically gives 50% de to the
same substrate. Moreover, Koga’s glutamic acid based auxil-
iary15,16 is a very efficient chiral director for asymmetric
conjugate addition of Li[PhMe2SiCuI] (entry 6). As a final
point, the present Li[PhMe2SiCuI] system is more attractive
than the introduced silylzincate, PhMe2SiZnEt2Li,9b because
yields are comparable, levels of diastereomeric excess are
higher, and the monosilylcopper reagent is easier to make.
As for the copper source, CuI purified via its dimethyl sulfide
(DMS) complex is crucial for the Li[PhMe2SiCuI] reagent to
undergo a smooth 1,4-addition reaction. Applying one equiva-
lent of the Aldrich 99.999% grade CuI, versus one equivalent of
LiSiMe2Ph in THF, without the presence of DMS, provided
only 50% of the b-silylated product (Scheme 1). The presence
of DMS has dramatic effects on the rate, stability and selectivity
of BuCu/LiI, as reported by Bertz.17 DMS remaining from the
purification process of CuI seems likely a component responsi-
ble for the higher yield, possibly due to a more soluble
silylcopper reagent. Additionally, the presence of DMS plays a
fundamental role in favoring the formation of one major
diastereomer in the conjugate addition. Thus, employing
Koga’s 2-pyrrolidinone (entry 7) and the Li[PhMe2SiCuI]
reagent made from the 99.999% grade CuI, in the absence of
DMS, not only lowered the yield from 92% to 63%, it also
reduced the diastereomeric ratio of the conjugate addition
product from 92% to 0% de! When DMS was combined with
the 99.999% grade CuI, the yield and the diasteromeric ratio of
the b-silylated product increased significantly (entry 8).
The CuI·DMS complex initially formed in the purification
process of CuI has been reported to be unstable and loses DMS
rapidly to form the more stable CuI·0.75DMS stoichiometry.11
At that point, the DMS concentration remains essentially
constant.18 A four month old sample of CuI·0.75DMS taken
from a light-protected bottle, gave identical yields and stereo-
selectivities in the conjugate addition reactions as a freshly
prepared sample of CuI·0.75DMS.
Notes and references
1 (a) E. W. Colvin, Silicon in Organic Synthesis, Butterworths, London,
1981; (b) W. P. Webber, Silicon Reagents in Organic Synthesis,
Springer, Berlin, 1983; (c) E. W. Colvin, Silicon Reagents in Organic
Synthesis, Academic Press, Orlando, FL, 1988; (d) M. A. Brook, Silicon
in Organic, Organometallic and Polymer Chemistry, Wiley, New York,
2000; (e) I. Fleming, A. Barbero and D. Walter, Chem. Rev., 1997, 97,
2063–2192.
2 (a) I. Fleming, R. Henning and H. Plaut, J. Chem. Soc., Chem.
Commun., 1984, 29–31; (b) I. Fleming and P. E. J. Sanderson,
Tetrahedron Lett., 1987, 28, 4229–4232; (c) I. Fleming, R. Henning, D.
C. Parker, H. E. Plaut and P. E. J. Sanderson, J. Chem. Soc., Perkin
Trans. 1, 1995, 317–337.
3 (a) K. Tamao, T. Tanaka, T. Nakajima, R. Sumiya, H. Arai and Y. Ito,
Tetrahedron Lett., 1986, 27, 3377–3380; (b) K. Tamao, A. Kawachi and
Y. Ito, J. Am. Chem. Soc., 1992, 114, 3989–3990.
4 (a) D. J. Ager, I. Fleming and S. K. Patel, J. Chem. Soc., Perkin Trans.
1, 1981, 2520–2526; (b) I. Fleming, in Organocopper Reagents—A
Practical Approach; ed. R. J. K Taylor, Oxford University Press,
Oxford, 1994, pp. 267–292, and references therein; (c) P. Perlmutter,
Conjugate Addition Reactions in Organic Synthesis, Pergamon Press,
Oxford, 1992.
5 For some developments of 1,4-additions of silyl groups, see (a) B. H.
Lipshutz, J. A, Sclafani and T. Takanami, J. Am. Chem. Soc., 1998, 120,
4021–4022; (b) H. Ito, T. Ishizuka, J. Tateiwa, M. Sonoda and A.
Hosomi, J. Am. Chem. Soc., 1998, 120, 11196–11197; (c) T. W. Lee and
E. J. Corey, Org. Lett., 2001, 3, 3337–3339.
6 (a) B. H. Lipshutz and B. James, J. Org. Chem., 1994, 59, 7585–7587;
(b) S. H. Bertz, G. Miao and M. Eriksson, Chem. Commun., 1996,
815–816.
7 As there is no evidence for the Cu–I bond, the monosilylcopper reagent
could also be depicted as PhMe2SiCu/LiI.
8 (a) K. Takaki, T. Maeda and M. Ishikawa, J. Org. Chem., 1989, 54,
58–62; (b) C. Palomo, J. M. Aizpurua, M. Iturburu and R. Urchegui, J.
Org. Chem., 1994, 59, 240–244.
9 (a) W. Tückmantel, K. Oshima and H. Nozaki, Chem. Ber., 1986, 119,
1581–1593; (b) R. A. N. C. Crump, I. Fleming and C. J. Urch, J. Chem.
Soc., Perkin Trans. 1, 1994, 701–706; (c) B. L. MacLean, K. A.
Hennigar, K. W. Kells and R. D. Singer, Tetrahedron Lett., 1997, 38,
7313–7316.
10 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 S. Sharma and A. C.
Oehlschlager, J. Org. Chem., 1989, 54, 5383–5387.
11 For a discussion on the stability of CuI/DMS complex, see E. Eriksson,
A. Hjelmencrantz, M. Nilsson and T. Olsson, Tetrahedron, 1995, 51,
12631–12644. See also M. Eriksson, T. Iliefski, M. Nilsson and T.
Olsson, J. Org. Chem., 1997, 62, 182–187.
12 Typically, reactions were conducted in 1 mmol scale ( ~ 60 mM, THF)
using 1.4–2.0 equivalents of Li[PhMe2SiCuI].
13 Li[PhMe2SiCuI]/DMS gives low yields of addition to b,b-disubstituted
enones. Additives, such as TMSI, MgBr2(OEt2), BF3OEt2, or Yb(OTf)3,
did not influence the yields of the desired products.
14 E. Nicolás, K. C. Russel and V. J. Hruby, J. Org. Chem., 1993, 58,
766–770. For conjugate additions of monoorganocuprate reagents,
Li[RCuI], to this substrate, see P. Pollock, J. Dambacher, R. Anness and
M. Bergdahl, Tetrahedron Lett., 2002, 43, 3693–3697.
15 K. Tomioka, T. Suenaga and K. Koga, Tetrahedron Lett., 1986, 27,
369–372.
16 I. Fleming and N. D. Kindon, J. Chem. Soc., Chem. Commun., 1987,
1177–1179.
This paper shows that excellent results in diastereoselective
conjugate additions can be obtained employing the mono-
silylcopper reagent, Li[PhMe2SiCuI]. It is suggested that the
CuI should be purified via its DMS complex prior to making the
monosilylcopper reagent. We have also demonstrated that
external additives such as tributylphosphine, HMPA, or dialkyl-
zinc are unnecessary, even though only one equivalent, not two,
of silyl lithium reagent is used. Employing the simple
Li[PhMe2SiCuI] reagent obtained from CuI, could be an
attractive alternative to the use of CuCN, which (although it
provides catalytic activity)5a is used in conjunction with
stoichiometric quantities of the R2Zn reagents. In summary, the
Li[PhMe2SiCuI] system is expected to be a very useful reagent,
for the chemo- and diastereoselective formation of silicon–
carbon bonds in organic synthesis.
17 S. H. Bertz and G. Dabbagh, Tetrahedron, 1989, 45, 425–434. See also
E. J. Corey and R. L. Carney, J. Am. Chem. Soc., 1971, 93, 7318–7319;
R. D. Clark and C. H. Heathcock, Tetrahedron Lett., 1974,
1713–1715.
This work was funded by RSCA and FGIA SDSU Founda-
tion. The authors wish to thank Dr Le Roy Lafferty and Dr Sam
Somanathan for technical assistance.
18 Confirmed by us using elemental analysis.
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