Chemistry of trichlorosilyl enolates. 1. New reagents for catalytic, asymmetric aldol additions

Full text of DOI:10.1021/ja9606539

7404
J. Am. Chem. Soc. 1996, 118, 7404-7405
Chart 1
Chemistry of Trichlorosilyl Enolates. 1. New
Reagents for Catalytic, Asymmetric Aldol Additions
Scott E. Denmark,* Stephen B. D. Winter, Xiping Su, and
Ken-Tsung Wong
Roger Adams Laboratory, Department of Chemistry
UniVersity of Illinois, Urbana, Illinois 61801
Scheme 1
ReceiVed February 28, 1996
The asymmetric aldol addition is among the most powerful
reactions in synthetic organic chemistry and has been extensively
studied over the past 15 years.1 The strategies for reagent-
controlled asymmetric induction fall into three broadly defined
classes (Chart 1): (1) asymmetric modification of the enolate
with chiral acyl auxiliaries (A), (2) asymmetric modification
of the enolate with chiral metalloid auxiliaries (B), and (3)
asymmetric modification of the aldehyde with chiral Lewis acids
(C). Each of these strategies has yielded spectacular success,
and each has unique advantages and disadvantages. The chiral
auxiliary approaches are extremely general and give high
selectivities by virtue of the highly ordered nature of the
transition structures (closed) which results from the structure
of R*/L* and the organizational features of the metal M.1a,c,2
Unfortunately, these reactions have yet to be made catalytic.
The chiral Lewis acid approach takes advantage of the Mu-
kaiyama aldol reaction3 of enoxysilane derivatives and is
demonstrably catalytic and often diastereo- and enantioselective.
However, these reactions are less general and the selectivity is
most likely dominated by van der Waals interactions which
guide the matching of enantiotopic faces in open transition
states.3,4
Scheme 2
We set for ourselves the goal of inventing a new type of aldol
addition reaction which involves the ordered preassembly of
enolate, aldehyde and chiral agent for maximum asymmetric
influence and which would be catalytic in the chiral reagent.
The formulation of this concept, Scheme 1, requires a metal
enolate moiety capable of expanding its valence by two and a
chiral Lewis base G*. The basis of this proposal for ligand-
promoted aldehyde additions finds precedent in our recently
disclosed asymmetric allylations (crotylations) with allylic
trichlorosilanes.5 We wish to report that the corresponding
trichlorosilyl enolates are highly reactiVe agents for the aldol
reaction and that their additions can be asymmetrically
catalyzed by chiral phosphoramides.
comparison.9 For the initial studies, the use of isolated, purified
trichlorosilyl enolates was deemed essential, and we followed
the general procedure of Baukov and Lutsenko,8a Scheme 2.
Thus, from methyl tributylstannylacetate (1)10 we could obtain
the trichlorosilyl ketene acetal 28a as a distillable liquid (bp 25
°C/5 mmHg),11 which thermally isomerized to methyl
(6) (a) Nakamura, E.; Kuwajima, I. Chem. Lett. 1983, 59. (b) Nakamura,
E.; Kuwajima, I. Tetrahedron Lett. 1983, 24, 3347. (c) Pridgen, L. N.; Abdel-
Magid, A.; Lantos, I. Tetrahedron Lett. 1989, 30, 5539. (d) Veronese, A.
C.; Gandolfi, V.; Basato, M.; Corain, B, J. Chem. Res. Synop. 1988, 246.
(e) Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Raimondi, L.
Tetrahedron 1994, 50, 5821. (f) For a general review of the chemistry of
tin enolates, see: Shibata, I.; Baba, A. Org. Prep. Proced. Int. 1994, 26,
85.
(7) The literature on reactions of trichlorotitanium enolates is vast. Only
leading papers containing previous references from representative labora-
tories are listed: (a) Yamago, S.; Machii, D.; Nakamura, E. J. Org. Chem.
1991, 56, 2098. (b) Harrison, C. R. Tetrahedron Lett. 1987, 28, 4135. (c)
Evans, D. A.; Duffy, J. L.; Dart, M. J. Tetrahedron Lett. 1994, 35, 8537.
(d) Evans, D. A.; Rieger, D. L.; Bilodeau, M. T.; Urpi, F. J. Am. Chem.
Soc. 1991, 113, 1047. (e) Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi,
F.; Ponzini, F.; Raimondi, L. Tetrahedron 1994, 50, 2939. (f) Yan, T.-H.;
Hung, A.-W.; Lee, H.-C.; Chang, C.-S.; Liu, W.-H. J. Org. Chem. 1995,
60, 3301. (g) Abrahams, I.; Motevalli, M.; Robinson, A. J.; Wyatt, P. B.
Tetrahedron 1994, 50, 12755. (h) Pridgen, L. N.; Abdel-Magid, A. F.;
Lantos, I.; Shilcrat, S.; Eggleston, D. S. J. Org. Chem. 1993, 58, 5107. (i)
Luke, G. P.; Morris, J. J. Org. Chem. 1995, 60, 3013.
(8) (a) Burlachenko, G. S.; Khasapov, B. N.; Petrovskaya, L. I.; Baukov,
Yu. I.; Lutsenko, I. F. J. Gen. Chem. USSR (Engl. Transl.) 1966, 36, 532.
(b) Lutsenko, I. F.; Baukov, Yu. I.; Burlachenko, G. S.; Khasapov, B. N.
J. Organomet. Chem. 1966, 5, 20. (c) Burlachenko, G. S.; Baukov, Yu. I.;
Dzherayan, T. G.; Lutsenko, I. F. J. Gen. Chem. USSR (Engl. Transl.) 1975,
45, 73. (d) Baukov, Yu. I.; Lutsenko, I. F. Moscow UniV. Chem. Bull. (Engl.
Transl.) 1970, 25, 72. (e) Ponomarev, S. V.; Baukov, Yu. I.; Dudukina, O.
V.; Petrosyan, I. V.; Petrovskaya, L. I. J. Gen. Chem. USSR (Engl. Transl.)
1967, 37, 2092. (f) Benkeser, R. A.; Smith, W. E. J. Am. Chem. Soc. 1968,
90, 5307. (g) Burlachenko, G. S.; Baukov, Yu. I.; Lutsenko, I. F. J. Gen.
Chem. USSR (Engl. Transl.) 1970, 40, 88.
While substantial literature exists on the generation and
reactions of trichlorostannyl6 and trichlorotitanium7 enolates,
the chemistry of trichlorosilyl enolates8 is embryonic by
(1) For reviews of enantioselective aldol additions see: (a) Evans, D.
A.; Nelson, J. V.; Taber, T. R. In Topics in Stereochemistry; Eliel, E. L.,
Allinger, N. L., Wilen, S. H., Eds.; Wiley Interscience: New York, 1982;
Vol. 13, p 1. (b) Heathcock, C. H. In ComprehensiVe Carbanion Chemistry;
Buncel, E., Durst, T., Eds.; Elsevier: New York, 1984; Vol. 5B, p 177. (c)
Heathcock, C. H. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic
Press: New York, 1984; Vol. 3, Chapter 2. (d) Kim, B. M.; Williams, S.
F.; Masamune, S. In ComprehensiVe Organic Synthesis. Additions to C-X
π Bonds; Heathcock, C. H., Ed.; Pergamon Press: Oxford; 1991; Vol. 2,
Part 2, pp 239-275. (e) Gennari, C. In ComprehensiVe Organic Synthesis.
Additions to C-X π Bonds; Heathcock, C. H., Ed.; Pergamon Press: Oxford;
1991; Vol. 2, Part 2, pp 629-660. (f) Bach, T. Angew. Chem., Int. Ed.
Engl. 1994, 33, 417. (g) Franklin, A. S.; Paterson, I. Contemp. Org. Synth.
1994, 1, 317-416. (h) Braun, M.; Sacha, H. J. Prakt. Chem. 1993, 335,
653-668. (i) Sawamura, M.; Ito, Y. In Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; VCH: New York, 1993; pp 367-388.
(2) Denmark, S. E.; Henke, B. R. J. Am. Chem. Soc. 1991, 113, 2177.
(3) (a) Mukaiyama, T. Org. React. 1982, 28, 203. (b) Mukaiyama, T.;
Murakami, M. Synthesis 1987, 1043. (c) Kobayashi, S.; Uchiro, H.; Shiina,
I.; Mukaiyama, T. Tetrahedron 1993, 49, 1761.
(4) Denmark, S. E.; Lee, W. J. Org. Chem. 1994, 59, 707.
(5) (a) Denmark, S. E.; Coe, D. M.; Pratt, N. E.; Griedel, B. D. J. Org.
Chem. 1994, 59, 6161. (b) Kobayashi has pioneered the use of formamides
as promoters of this reaction; see: Kobayashi, S.; Nishio, K. J. Org. Chem.
1994, 59, 6620.
S0002-7863(96)00653-1 CCC: $12.00 © 1996 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 118, No. 31, 1996 7405
Table 1. Aldol Reactions of 2 with Pivalaldehyde: Solvent and
Table 3. Catalytic Asymmetric Aldol Reactions of 2: Survey of
Additive Effectsa
Promotersa
entry
solvent
promoter, equiv
conversion/time,b %/min
entry
aldehyde
promoter, equiv
product
eeb (yieldc), %
1
2
3
4
toluene-d8
CD2Cl2
THF-d8
CD2Cl2
none
none
none
HMPA (0.1)
18/120
50/120
69/120
100/<3
1
2
PhCHO
PhCHO
PhCHO
PhCHO
5 (0.1)
6 (0.1)
7 (0.1)
6 (0.1)
6 (1.0)
5 (0.1)
6 (0.1)
7 (0.1)
7 (0.1)
7 (1.0)
(R)-4a
(S)-4a
(S)-4a
(S)-4a
(S)-4a
(R)-4f
(S)-4f
(S)-4f
(S)-4f
(S)-4f
20 (88)
33 (87)
23 (91)
38 (94)
53 (84)
26 (76)
40 (78)
49 (75)
50 (78)
62 (77)
3
4d
5
PhCHO
a Reactions monitored by 1H NMR (500 MHz) at -80 °C. b Percent
consumption of pivalaldehyde.
6
7
t-BuCHO
t-BuCHO
t-BuCHO
t-BuCHO
t-BuCHO
8
Table 2. Preparative Aldol Reactions of 2a
9d
10
a All reactions performed at -78 °C/0.1 M. b Determined by chiral
HPLC. c Chromatographically homogeneous material. d Slow addition
of aldehyde.
Scheme 3
R1
phenyl
R2
product
yield,b %
H
H
H
H
H
H
4a
4b
4c
4d
4e
4f
98
94
89
96
96
99c
97d
benzyl
(E)-cinnamyl
2-phenethyl
cyclohexyl
tert-butyl
phenyl
methyl
4g
a All reactions carried out at a 1.0 mmol scale. b Yields of analytically
pure material. c Reaction run at 20 °C. d Reaction run at 20 °C/0.5 M
with 10 mol % of HMPA.
benzaldehyde were initially disappointing with enantioselec-
tivities <40% ee. No improvement was observed with changes
in solvent (THF, toluene) or temperature (-90, 0 °C). The
enhanced selectivity (53% ee, entry 5) obtained with 1.0 equiv
of 6 confirmed that the background reaction was competitive
even at -80 °C.
Chart 2
The results with pivalaldehyde are also in accord with that
hypothesis. For all of the promoters examined, the enantio-
selectivity was superior, although interestingly the best selectiv-
ity (50% ee) was obtained with 7. The intervention of the
nonpromoted pathway with pivaladehyde was suggested as well
by the improved selectivity observed with 1.0 equiv of 7 (entry
10).
trichlorosilylacetate.8d Similarly, 1-((tributylstannyl)oxy)cyclo-
hexene12 underwent clean metathesis to the trichlorosilyl enolate
of cyclohexanone (3) (bp 76-78 °C/11 mmHg).8e,11
The ketene acetal 2 reacted spontaneously with a number of
aldehydes at -80 °C (VT-NMR observation). Only pivalal-
dehyde reacted slowly enough to be followed spectroscopically.
The results in Table 1 show a solvent effect on the rate of
reaction at -80 °C. However, most exciting is the acceleration
observed with a catalytic amount of HMPA (entries 2 and 4).
The preparative utility of the unpromoted reactions was
demonstrated by the survey of aldehydes shown in Table 2.
The aldol addition products 4 were obtained analytically pure
in excellent yield. The range of substrates attests to the
generality of the reaction and the compatibility of branched and
highly enolizable aldehydes. No evidence of 1,4-type addition
with cinnamaldehyde was observed. Remarkably, even
acetophenone gave the acetate adduct (with HMPA at 20 °C).
The demonstration of catalysis by HMPA clearly presaged
the use of chiral phosphoramides. The promoters11 (5,5a 6,
and 7) shown in Chart 2 were all surveyed with both benzal-
dehyde and pivalaldehyde, and the results are collected in Table
3.
Preliminary results from the reaction of enoxychlorosilane 3
show that the chiral Lewis base promoted aldol addition has
significant synthetic potential, Scheme 3. In combination with
benzaldehyde and (E)-cinnamaldehyde, the anti aldol products
8 were obtained in excellent diastereoselectivity (65-99/1) and
very good enantioselectivity (88-93% ee)13 with catalytic
amounts (10 mol %) of promoter 6.
While it is not possible to construct rational transition state
structures for the promoted aldol additions, our working
hypothesis is a classic chairlike arrangement of reactive partners
assembled around a hexacoordinate siliconate species. Methods
for in situ generation of trichlorosilyl enolates, exploration of
modulated chlorosilyl enolates, and optimization of promoter
structure are currently under investigation.
Acknowledgment. We are grateful to the National Science Founda-
tion for generous financial support (CHE 9500397). X.S. thanks the
University of Illinois for a graduate fellowship.
All promoted reactions of 2 were initially carried out at -78
°C in CH2Cl2 with 10 mol % of the promoter. The results with
Supporting Information Available: Procedures for the preparation
and full characterization of 1, 2, 3, 4a-g, (S)-4a, (S)-4f, 6, 7 (-)-anti-
8a, and (+)-anti-8b (25 pages). See any current masthead page for
ordering and Internet access instructions.
(9) For reports on the preparation of other chlorosilyl enolates, see: (a)
Walkup, R. D. Tetrahedron Lett. 1987, 28, 511. (b) Walkup, R. D.;
Obeyesekere, N. U.; Kane, R. R. Chem. Lett. 1990, 1055. (c) Kaye, P. T.;
Learmonth, R. A.; Ravindran, S. S. Synth. Commun. 1993, 23, 437.
(10) Zapata, A.; Acun˜a A. C. Synth. Commun. 1984, 14, 27.
(11) All compounds described herein were fully characterized by
spectroscopic and analytical methods. See the supporting information.
(12) (a) Pereyre, M.; Bellegarde, B.; Mendelsohn, J.; Valade, J. J.
Organomet. Chem. 1968, 11, 97. (b) Yasuda, M.; Katoh, Y.; Shibata, I.;
Baba, A.; Matsuda, H.; Sonoda, N. J. Org. Chem. 1994, 59, 4386.
JA9606539
(13) The absolute configuration of (-)-anti-8a has been determined to
be (2R,1′S) by X-ray analysis of the 4-bromobenzoate derivative. This will
be described in a full account.