Catalytic enantioselective isomerization of silacyclopentene oxides: New strategy for stereocontrolled assembly of acyclic polyols

Article abstract of DOI:10.1002/1521-3773(20011217)40:24<4757::AID-ANIE4757>3.0.CO;2-S

A versatile precursor for the assembly of a range of polyol-containing fragment is the silacyclic alcohol 2 that results from the highly enantioselective, calalytic isomerization of diphenylsilacyclopentene oxide (1). The use of this precursor is illustrated with the efficient and highly diastereoselective assembly of acyclic tetraol motifs.

Full text of DOI:10.1002/1521-3773(20011217)40:24<4757::AID-ANIE4757>3.0.CO;2-S

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[7] The reaction of 7 withAuCl 3 as catalyst afforded exclusively phenol 8
(69%).[3] In the platinum(ii)-catalyzed reaction, traces (ca. 1%) of a
phenol tentatively assigned as 1,3-dihydro-6-methyl-5-isobenzofura-
nol were also obtained.
Catalytic Enantioselective Isomerization of
Silacyclopentene Oxides: New Strategy for
Stereocontrolled Assembly of Acyclic
Polyols**
[8] a) The calculations were performed with Gaussian98.[8b] The geo-
metries of all complexes were optimized at the DFT level of theory
with the generalized gradient approximation and the B3LYP hybrid
functional.[8c, d] The standard 6-31G(d) basis set was used for C, H, O
and Cl, and the default LANL2DZ pseudorelativistic potential and
basis set were used for Pt. Harmonic frequencies were calculated at
B3LYP level to characterize the stationary points and to determine
the zero-point energies (ZPE). The starting approximate geometry for
the transition states (TS) were located graphically; b) Gaussian98
(RevisionA.7), M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E.
Scuseria, M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A.
Montgomery, R. E. Stratmann, J. C. Burant, S. Dapprich, J. M.
Millam, A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi,
V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo,
S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K.
Morokuma, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B.
Foresman, J. Cioslowski, J. V. Ortiz, B. B. Stefanov, G. Liu, A.
Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin, D. J.
Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, C.
Gonzalez, M. Challacombe, P. M. W. Gill, B. G. Johnson, W. Chen,
M. W. Wong, J. L. Andres, M. Head-Gordon, E. S. Replogle, J. A.
Pople, Gaussian, Inc., Pittsburgh, PA, 1998.; c) P. J. Stephens, F. J.
Devlin, C. F. Chabalowski, M. J. Frisch, J. Phys. Chem. 1994, 98,
11623 11627; d) W. Kohn, A. D. Becke, R. G. Parr, J. Phys. Chem.
1996, 1000, 12974 12980.
Dong Liu and Sergey A. Kozmin*
Creation of molecular chirality by desymmetrization of
readily available prochiral precursors is a powerful synthetic
strategy.[1] This approach is particularly attractive when a
substoichiometric amount of chiral catalyst is utilized to
mediate suchtransformations withhighefficiency and enan-
tioselectivity.[2] We have been engaged in the development of
new catalytic desymmetrization approaches based on the use
of cyclic silicon-containing templates. Herein, we disclose a
highly enantioselective base-promoted rearrangement of
silacyclopentene oxide, which resulted in the development
of a novel strategy for the preparation of acyclic polyol-
containing motifs. To our knowledge, enantioselective de-
symmetrization of cyclic silanes has not been documented
prior to this work.[3, 4]
Pioneered by Whitesell and Felman,[5] base-mediated
epoxide isomerization utilizing chiral lithium amides has
become a valuable method for the preparation of allylic
alcohols.[6] Withthis as a precedent, we devised a strategy for
desymmetrization of meso-silane A (Scheme 1). Enantiose-
lective deprotonation, followed by b-elimination would result
in the formation of enantiomerically enriched allylic alcohol
B. Importantly, the use of a catalytic amount of chiral base in
combination withan appropriate agent capable of regenerat-
[9] Bond lengths, bond angles, and atomic coordinates for the structures
of Figure 1 are given in the Supporting Information.
[10] a) A mechanistic hypothesis for the formation of dihydrofurans from
XI is outlined in the Supporting Information; b) we have previously
observed the formation of an aldehyde from a related platinum
carbene intermediate;[1b] c) for the related oxidation of a nickel
carbene intermediate, see: S. K. Chowdhury, K. K. D. Amarasinghe,
M. J. Heeg, J. Montgomery, J. Am. Chem. Soc. 2000, 122, 6775 6776.
[11] Rhodium carbenes, generated in situ from [Rh2(OAc)4] and diazo
compounds, react withaldehydes to form epoxides. See, for example,
a) V. K. Aggarwal, H. Abdel-Rahman, R. V. H. Jones, H. Y. Lee, B. D.
Reid, J. Am. Chem. Soc. 1994, 116, 5973 5974; b) M. Hamaguchi, H.
Matsubara, T. Nagai, Tetrahedron Lett. 2000, 41, 1457 1460.
[12] Trapping of an intermediate alkenylmetal intermediate withallyl
¬
¬
chloride: C. Fernandez-Rivas, M. Mendez, A. M. Echavarren, J. Am.
Chem. Soc. 2000, 122, 1221 1222.
[13] a) K. Kaneda, T. Uchiyama, Y. Fujiwara, T. Imanaka, S. Teranishi, J.
Org. Chem. 1979, 44, 55 63; b) J.-E. B‰ckvall, Y. I. M. Nilsson,
R. G. P. Gatti, Organometallics 1995, 14, 4242 4246, and references
therein.
Scheme 1. General strategy for the desymmetrization of meso-silane A to
give enatiomerically enriched allylic alcohol B.
[*] Prof. Dr. S. A. Kozmin, D. Liu
Department of Chemistry
University of Chicago
5735 SouthEllis Avenue
Chicago, IL 60637 (USA)
Fax : (‡1)773-702-0805
E-mail: skozmin@uchicago.edu
[**] Initial funding of this work was provided by the University of Chicago.
We are grateful to the donors of the Petroleum Research Fund for
further financial support.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
Angew. Chem. Int. Ed. 2001, 40, No. 24
¹ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
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ing the active catalyst would result in the development of a
catalytic enantioselective process.[7] Silane B, which incorpo-
rates structural features of boththe vinyl silane and allylic
alcohol, was envisioned to serve as a versatile precursor for
the assembly of a wide range of synthetically valuable acyclic
polyol fragments.
ers for the rearrangement of carbocyclic epoxides.[10] While
91% ee was obtained witha 5 mol% loading, the use of
10 mol% of amide 4 resulted in 93% ee and 78% yield
(Scheme 3).[11, 12]
Silacyclopentene oxides can be readily assembled on a
preparative scale according to the general sequence illustrat-
ed in Scheme 2. In the case of the diphenyl-substituted
derivative, silylation of magnesium butadiene,[8] followed by
oxidation of the resulting silacyclopentene 1 with3-chloro-
peroxybenzoic acid (MCPBA) furnished epoxide 2 in an
overall yield of 80% for the two steps.[9]
Scheme 3. Catalytic enantioselective isomerization of 2 to give (‡)-3a.
Having secured an efficient access to alcohol (‡)-3a in high
enantiomeric purity, our subsequent efforts focused on the
stereoselective construction of tetraol fragment 12 (see
Table 2). The approach commenced with a diastereoselective
hydroxy-directed epoxidation of (‡)-3a to give (À)-10 (d.r.:
>97:3),[9] followed by Si-guided cuprate addition to afford
silacyclic diol 11 (Table 1).[13] The latter transformation was
found to be highly regioselective and general for incorporat-
ing a variety of alkyl, aryl, and alkenyl fragments. Importantly,
potential products resulting from either the Peterson elimi-
nation or fragmentation were not observed under these highly
nucleophilic conditions.
Our studies on the oxidative cleavage of silacyclic diols 11
began with the examination of the Tamao[14] and the Flem-
ing[15] protocols, which generally resulted in incomplete
reactions and isolation of multiple products. We soon
uncovered that the oxidative cleavage of the silacyclopentane
Scheme 2. Preparation of diphenylsilacyclopentene oxide (2).
We anticipated that the presence of the silicon atom would
have two beneficial effects on the epoxide rearrangement: 1)
a-Si-carbanion stabilization favoring initial deprotonation;
and 2) the ability to maximize the level of asymmetric
induction by adjusting the exocyclic silicon substituents
positioned in the direct proximity to the deprotonation site.
Systematic cross-examination of three silacyclopentene ox-
ides and four chiral amide bases (Figure 1) revealed that the
Table 1. Epoxidation/cuprate addition sequence.[a]
Entry
R
11
Yield [%][b]
91[c]
d.r.
1
2
(À)-11a
(À)-11a
> 97:3
> 97:3
72[d]
3
(À)-11b
78[c]
> 97:3
4
5
6
7
8
9
(À)-11c
(À)-11d
(À)-11e
(À)-11 f
(À)-11g
(À)-11 f
92[c]
87[c]
92[c]
86[c]
91[d]
64[e]
> 97:3
> 97:3
> 97:3
> 97:3
> 97:3
> 97:3
Figure 1. Base-mediated rearrangement of silacyclopentene oxides 2 to
give allylic alcohols 3.
use of diphenylsilacyclopentene oxide 2a in combination with
bicyclic amide 4[10] resulted in the highest level of enantiose-
lectivity (95% ee). Furthermore, we found that the rearrange-
ment can be performed efficiently using a catalytic amount of
4 and two equivalents of lithium disopropylamide (LDA), in
agreement withresults obtained by Andersson and co-work-
[a] For detailed experimental procedures and compound characterization,
see Supporting Information. [b] Refers to the yield of spectroscopically
pure product isolated after silica gel chromatography. [c] Organocuprate
was generated from the corresponding Grignard reagent. [d] Organo-
cuprate was generated from the corresponding organolithium reagent.
[e] Reduction was carried out on the methoxymethyl(MOM)-protected
alcohol (À)-10 to prevent formation of the meso product.
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Table 2. Oxidative cleavage of cyclic silanes.[a]
[6] For reviews, see: a) J. K. Crandall, M. Apparu, Org. React. 1983, 29,
345; b) D. M. Hodgson; A. R. Gibbs, G. P. Lee, Tetrahedron 1996, 52,
14361; c) P. O×Brien, J. Chem. Soc. Perkin Trans. 1 1998, 1439.
[7] For a pioneering investigation on catalytic enantioselective isomer-
ization of carbocyclic epoxides, see: M. Asami, T. Ishizaki, S. Inoue,
Tetrahedron: Asymmetry 1994, 5, 793.
[8] a) W. J. Richter, Synthesis 1982, 1102; b) S. Mignani, D. Damour, J.-P.
Bastart, G. Manuel, Syn. Commun. 1995, 25, 3855.
[9] G. Manuel, R. Boukherroub, J. Organomet. Chem. 1993, 447, 167.
[10] a) M. J. Sˆdergren, P. G. Andersson, J. Am. Chem. Soc. 1998, 120,
10760; b) M. J. Sˆdergren, S. K. Bertilsson, P. G. Andersson, J. Am.
Chem. Soc. 2000, 122, 6610.
[11] Determination of the enantiomeric excess was carried out by the
Mosher ester 1H NMR analysis; see Supporting Information for
details. The attempts to resolve alcohol 3a using six different chiral
HPLC stationary phases proved unsuccessful.
[12] The absolute configuration of silane (R)-3a was later confirmed by its
conversion to the known (S)-triol 9, as illustrated below.
Entry
1
Silane
R
R'
12
Yield [%][b]
78
(À)-11a
H
(À)-12a
2
(‡)-11b
H
(À)-12b
76
3
4
5
(‡)-11c
(À)-11 f
(À)-11h
H
(À)-12c
(À)-12d
(À)-12e
79
70
74
H
MOM
[a] For detailed experimental procedures and compound characterization,
see Supporting Information. [b] Refers to the yield of spectroscopically
pure product isolated after silica gel chromatography.
scaffold can be efficiently accomplished according to the
Woerpel procedure employing the use of basic tBuOOH in
DMF.[16] Several representative tetraols 12 were prepared in
good yields with complete overall diastereoselectivity illustrat-
ing the generality of this strategy (Table 2). The occurrence of
a polyol motif 12 in a number of bioactive natural products is
noteworthy. Representative examples include the side chain
portion of bacteriohopanoid.[17a] and the central macrolide
segment of herbarumin I, a highly potent phytotoxic agent.[17b]
In summary, we have demonstrated a highly enantioselec-
tive catalytic isomerization of silacyclopentene oxide, a
pivotal point in our strategy for the stereoselective assembly
of acyclic polyols. Development of an arsenal of new
asymmetric processes utilizing cyclic silanes is currently in
progress.
[13] K. Tamao, E. Nakajo, Y. Ito, J. Org. Chem. 1987, 52, 4414.
[14] K. Tamao, M. Kumada, K. Maeda, Tetrahedron Lett. 1984, 321.
[15] I. Fleming, P. E. Sanderson, Tetrahedron Lett. 1987, 28, 4229.
[16] J. H. Smitrovich, K. A. Woerpel, J. Org. Chem. 1996, 61, 6044.
[17] a) N. Zhao, N. Berova, K. Nakanishi, M. Rohmer, P. Mougenot, U. J.
Jurgens, Tetrahedron 1996, 52, 2777; b) J. F. River-Cruz, G. Garcia-
Aguirre, C. M. Cerda-Garcia-Rojas, R. Mata, Tetrahedron 2000, 56,
5337.
The First Catalytic, Diastereoselective, and
Enantioselective Crossed-Aldol Reactions of
Aldehydes**
Received: September 6, 2001 [Z17864]
[1] a) T.-L. Ho, Symmetry: A Basis for Synthetic Design, Wiley, New
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Scott E. Denmark* and Sunil K. Ghosh
[2] For selected examples of catalytic enantioselective desymmetriza-
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[3] For the use of cyclic siloxanes in stereoselective synthesis, see: a) K.
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Chem. Soc. 1986, 108, 6090; b) S. H. Bergens, P. Noheda, J. Whelan, B.
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Bodnar; W. S. Palmer, J. T. Shaw, J. H. Smitrovich, J. D. Sonnenberg,
A. L. Presley, K. A. Woerpel, J. Am. Chem. Soc. 1995, 117, 10575, and
references therein.
The apotheosis of the aldol addition reaction is one of the
most well-documented chapters of modern organic synthesis;
the generality, versatility, and selectivity associated with this
process have been the subject of countless reviews and
authoritative summaries. Stimulated by the challenge posed
by nature, a generation of synthetic organic chemists has
constructed an impressive edifice of knowledge which con-
stitutes insightful, elegant, and practical solutions to the
structural and stereochemical problems presented by poly-
propionate-derived natural products. Yet, at this advanced
vantage, it is remarkable that the most basic of aldol
[*] Prof. Dr. S. E. Denmark, Dr. S. K. Ghosh
Department of Chemistry, University of Illinois
Urbana, IL 61801 (USA)
Fax : (‡1)217-333-3984
E-mail: denmark@scs.uiuc.edu
[**] We are grateful to the National Science Foundation for generous
financial support (NSF CHE 9803124).
[4] For reviews on preparation and properties of cyclic silanes, see: a) J.
Hermanns, B. Schmidt, J. Chem. Soc. Perkin. Trans. 1 1998, 2209; b) J.
Hermanns, B. Schmidt, J. Chem. Soc. Perkin. Trans. 1 1999, 81.
[5] J. K. Whitesell, S. W. Felman, J. Org. Chem. 1980, 45, 755.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
Angew. Chem. Int. Ed. 2001, 40, No. 24
¹ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4024-4759 $ 17.50+.50/0
4759