J. Am. Chem. Soc. 2001, 123, 12095-12096
12095
Table 1. Enantioselective Addition Reactions of Allenylsilanes 2a
Highly Enantioselective Syntheses of
Homopropargylic Alcohols and Dihydrofurans
Catalyzed by a Bis(oxazolinyl)pyridine-Scandium
Triflate Complex
David A. Evans,* Zachary K. Sweeney, Tomislav Rovis, and
Jason S. Tedrow
Department of Chemistry & Chemical Biology
HarVard UniVersity, Cambridge, Massachusetts 02138
ReceiVed August 16, 2001
Lewis acid promoted reactions of allylsilanes and allenylsilanes
provide access to important building blocks for natural product
synthesis.1 For example, trimethylsilylallenes function as prop-
argylic anion equivalents in aldehyde addition reactions (eq 1,
Path A).2 If the silicon center is sterically congested, the normal
addition pathway is suppressed and functionalized dihydrofurans
are produced (eq 1, Path B).3 Although both transformations may
be promoted by stoichiometric amounts of titanium tetrachloride,
enantioselective reactions of allenylsilanes have not been re-
ported.4 In this Communication, we describe highly enantiose-
lective scandium triflate catalyzed addition and annulation
reactions of allenylsilanes with ethyl glyoxylate.
a Unless otherwise noted, all reactions were carried out in CH2Cl2
for 16 h at -55 °C with 10 equiv of HFIP and 10 mol% 1.
b Enantiomeric excess determined by GLC using a Cyclodex-B or
Gamma-TA column. c Reaction run at 0 °C.
or branched alkyl substituents. When the less reactive 1-phenyl-
1-(trimethylsilyl)allene (2e) was used as a substrate, it was
necessary to warm the reaction mixture to 0 °C to ensure complete
conversion of the allene (entry 5, 97% ee, 63% yield).
As expected, [3+2] cycloaddition products are produced when
the steric bulk of the silane substituents is increased.3 Dihydro-
furan 5 was isolated in excellent yield (>98%) and enantiomeric
excess (89% ee) when scandium complex 1 was used as a catalyst
for the reaction between 1-methyl-1-(triisopropyl)allene (4) and
ethyl glyoxylate (10 mol % 1, CH2Cl2, -45 °C, eq 3).7 The
sterically demanding silicon substituents completely altered the
course of the reaction, and no addition products were observed
in the 1H NMR spectra of unpurified reaction mixtures. Variation
in the silyl group of the allenylsilane component revealed that
the tert-butyldiphenylsilyl functionality was optimal for this
process (92% ee).
Initial investigations revealed that [Sc(S,S)-Ph-pybox](OTf)3
complex (1)5 (10 mol %, CH2Cl2, -55 °C) promotes the addition
of 1-methyl-1-(trimethylsilyl)allene (2a) to ethyl glyoxylate (eq
2) to afford (R)-3a in high enantioselectivity following desilylation
with K2CO3/EtOH (98% ee, 95% yield).6 The catalyst does not
appear to be affected by small amounts of water (ca. 1 equiv) or
alcohol (10 equiv), and yields were slightly improved when
hexafluoro-2-propanol (HFIP) was added to the reaction mixture.
This additive suppresses the formation of oligomeric byproducts,
but does not influence either the catalyst activity or the reaction
enantioselectivity. The scope of this reaction is summarized in
Table 1. The scandium triflate complex 1 affords good enanti-
oselectivities and yields with allenylsilanes containing either linear
Several (tert-butyldiphenylsilyl)allenes were prepared and
employed in the annulation reaction (Table 2). Alkyl-substituted
allenes provided the corresponding dihydrofurans in good yields
(63-91%) and enantioselectivities (91-94% ee). To demonstrate
the practicality of the catalyzed [3+2] annulation, the reaction
between 6a and ethyl glyoxylate was performed with 3.5 mmol
of 6a and 5 mol % of readily available catalyst 1 to produce 1.2
g of 7a (94% ee, 91% yield, entry 2). The phenyl-substituted
allenylsilane 6g was poorly nucleophilic, and 7g was isolated in
low yield (entry 9). An X-ray crystal structure of 7g confirmed
the connectivity of the products while the absolute configuration
of 7a was determined by crystallographic analysis of the (S)-R-
methylbenzylamide derivative (see Supporting Information).
The dihydrofurans and homopropargylic alcohols described in
this study afford useful chiral synthons. The vinylsilane func-
tionality in dihydrofurans 7 is nucleophilic, and can be acylated
(1) (a) Hirashima, S.; Aoyagi, S.; Kibayashi, C. J. Am. Chem. Soc. 1999,
121, 9873-9874. (b) Aoyagi, S.; Hasegawa, Y.; Hirashima, S.; Kibayashi,
C. Tetrahedron Lett. 1998, 39, 2149-2152. (c) Marshall, J. A.; Maxon, K. J.
Org. Chem. 2000, 65, 630-633. (d) Gauthier, D. R.; Carreira, E. M. Angew.
Chem., Int. Ed. 1996, 35, 2363-2365. (e) Mikami, K.; Nakai, T. In Catalytic
Asymmetric Synthesis, 2nd ed.; Ojima, O. ,Ed.; Wiley-VCH: New York, 2000;
Chapter 8C.
(2) (a) Danheiser, R. L.; Carini, D. J. J. Org. Chem. 1980, 45, 3927-
3928. (b) Danheiser, R. L.; Carini, D. J.; Kwasigroch, C. A. J. Org. Chem.
1986, 51, 3870-3878.
(3) Danheiser, R. L.; Kwasigroch, C. A.; Tsai, Y.-M. J. Am. Chem. Soc.
1985, 107, 7233-7235.
(4) For catalyzed addition reactions of 1-(tributylstannyl)-1,2-propadiene
see: (a) Keck, G. E.; Krishnamurthy, D.; Chen, X. Tetrahedron Lett. 1994,
35, 8323-8324. (b) Yu, C.-M.; Yoon, S.-K.; Choi, H.-S.; Baek, K. Chem.
Commun. 1997, 763-764. (c) Denmark, S. E.; Wynn, T. J. Am. Chem. Soc.
2001, 123, 6199-6200.
(5) (S,S)-Ph-pybox ) [(S)-(R*,R*)]-2,6-bis(4,5-dihydro-4-phenyl-2-oxazolyl)-
pyridine. Both enantiomers of this ligand, as well as scandium(III) triflate,
are commercially available.
(6) The absolute stereochemistry of product 3b was established by
hydrogenation with Pd/C to produce ethyl (R)-2-hydroxynonanoate and
comparison of the spectral data and optical rotation of this material with that
reported in the literature. The remaining adducts are assigned the indicated
configuration by analogy. See Supporting Information.
(7) Other catalysts were either less active or less selective: Cu((S,S)-tBu-
box)(SbF6)2, 21% ee, -78 °C; Cu((S,S)-tBu-box)(OTf)2, 45% ee, 0 °C; Cu-
((S,S)-Ph-pybox)(SbF6)2, 80% ee, -78 °C to room temperature, (incomplete
reaction). See: (a) Evans, D. A.; Johnson, J. S. Acc. Chem. Res. 2000, 33,
325-335. (b) Evans, D. A.; Rovis, T.; Johnson, J. S. Pure Appl. Chem. 1999,
71, 1407-1415.
10.1021/ja011983i CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/09/2001