C O M M U N I C A T I O N S
Scheme 2
is unreactive with 1 (Scheme 3).6 These results are consistent with
a modified mechanism in which the acyl oxygen becomes covalently
attached to the silane reagent by chloride displacement, and only
then does allylation occur.
Figure 1. X-ray structure of 11.
addition, while it is clear that the success of these reactions is due
at least partly to the fact that the allylation is rendered intramo-
lecular, it may also be true that the protonation of the amine of the
pseudoephedrine is responsible for increased Lewis acidity of the
silane as well.9
Scheme 3
A highly practical method for the enantioselective synthesis of
tertiary carbinamines has been reported. Reagent 1 is easily prepared
in bulk, the experimental procedures are trivial, the products may
be isolated (no chromatography) in high ee by crystallization, and
the pseudoephedrine controller may be recovered in high yield by
simple extraction.
Acknowledgment. We are grateful to Dr. Kevin Janak and
Guang Zhu (Parkin research group) for the X-ray structure analysis
of 11. We thank Merck Research Laboratories for unrestricted
research support and fellowship support of R.B. We thank Amgen
and the Yamanouchi USA Foundation for research support. K.D.
was supported by the NSF-REU program.
To gain direct evidence for this hypothesis, we have prepared
phenylsilane 7 (isolated as a 2:1 mixture of diastereomers). Upon
reaction of 7 with hydrazone 8 in CDCl3, 1H NMR analysis shows
the disappearance of 7 and 8 and the clean appearance of four new
sets of signals that are consistent with structures such as 9 or 10
(Scheme 4).7
Supporting Information Available: Experimental procedures,
characterization data, and stereochemical proofs (PDF, CIF). This
Scheme 4
References
(1) For reviews, see: (a) Cativiela, C.; D´ıaz-de-Villegas, M. D. Tetrahe-
dron: Asymmetry 1998, 9, 3517. (b) Gro¨ger, H. Chem. ReV. 2003, 103,
2795. See also: (c) Saaby, S.; Nakama, K.; Lie, M. A.; Hazell, R. G.;
Jørgensen, K. A. Chem.-Eur. J. 2003, 9, 6145 and references therein.
(2) For reviews, see: (a) Steinig, A. G.; Spero, D. M. Org. Prep. Proced.
Int. 2000, 32, 205. (b) Enders, D.; Reinhold, U. Tetrahedron: Asymmetry
1997, 8, 1895.
(3) (a) Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35,
984. (b) Cogan, D. A.; Ellman, J. A. J. Am. Chem. Soc. 1999, 121, 268.
(c) Hua, D. H.; Miao, S. W.; Chen, J. S.; Iguchi, J. J. Org. Chem. 1991,
56, 4.
(4) (a) Berger, R.; Rabbat, P. M. A.; Leighton, J. L. J. Am. Chem. Soc. 2003,
125, 9596. For other recent reports concerning stereoselective allylation
of hydrazones, see: (b) Friestad, G. K.; Ding, H. Angew. Chem., Int. Ed.
2001, 39, 4491. (c) Kobayashi, S.; Ogawa, C.; Konishi, H.; Sugiura, M.
J. Am. Chem. Soc. 2003, 125, 6610.
(5) (a) Hirabayashi, R.; Ogawa, C.; Sugiura, M.; Kobayashi, S. J. Am. Chem.
Soc. 2001, 123, 9493. (b) Ogawa, C.; Sugiura, M.; Kobayashi, S. J. Org.
Chem. 2002, 67, 5359. (c) Ding, H.; Friestad, G. K. Org. Lett. 2004, 6,
637.
(6) Aldehydes are allylated by 5, establishing that it is an otherwise competent
allylation reagent. Leighton, J. L.; Lombardi, P. J. Unpublished results.
(7) The N-CH3 peak is a doublet, for example. See the Supporting
Information.
(8) Many X-ray structures of pentacoordinated silicon compounds have been
reported. See: Holmes, R. R. Chem. ReV. 1996, 96, 927.
(9) (a) Ryu, D. H.; Lee, T. W.; Corey, E. J. J. Am. Chem. Soc. 2002, 124,
9992. (b) Ryu, D. H.; Corey, E. J. J. Am. Chem. Soc. 2003, 125, 6388.
This mixture precipitated as a white powder 11 (a single
compound by H NMR analysis) in 90% yield from toluene, and
1
X-ray quality crystals were obtained by recrystallization from a
CH2Cl2/hexanes solution (Figure 1). Not only does this structure
strongly support the proposed chloride-displacement mechanism,
it also represents the first X-ray structure of a silane Lewis acid-
Lewis base complex directly relevant to an asymmetric reaction.8
One particularly notable feature is the isomerization of the CdN
double bond from E in 8 to Z in 11. This provides direct evidence
for the feasibility of the E:Z isomerization in these reactions that
is clearly suggested by entry 14 in Table 1. In this context, it is
noteworthy as well that substitution of allyl for phenyl on the silicon
in structure 11 would lead to a prediction of the observed sense of
induction.
This revised mechanism has profound implications for the further
development of this chemistry. Certainly new substrates that carry
functionality capable of adding to the silane may be imagined. In
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