C O M M U N I C A T I O N S
Table 2. Enantioselective Addition of Silyl Ketene Acetal 8b To
Provide Substituted Isochromans
determining step, it is consistent with an oxocarbenium chloride-thiourea
complex as the reactive electrophilic species.17,18
This work brings oxocarbenium ions into the realm of viable
electrophilic substrates for asymmetric catalysis. Taken together with
our previously described reactions of N-acyliminium ions, thiourea
catalysis by anion binding provides a general mechanism for enanti-
oselective additions to cationic intermediates. We anticipate that this
mode of catalysis will find use in related reactions of oxocarbenium
ions, such as diastereoselective glycosyl bond formation, and this is
the focus of ongoing research.19
Acknowledgment. This work was supported by the NIGMS (GM-
43214), by predoctoral fellowship support to A.G.D. from the NSF,
and postdoctoral fellowship to S.E.R. from the NIH. We thank Dr.
Kevin Campos (Merck Process) for helpful discussions and generous
donations of N-Boc-2-arylpyrrolidine derivatives.
Supporting Information Available: Experimental procedures and
characterization data. This material is available free of charge via the
a Isolated yield (based on 6) after silica gel chromatography.
b Determined by HPLC analysis using commercial chiral columns.
References
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Figure 1. Addition of tetrasubstituted silyl ketene acetals to provide
substituted isochromans.
derivatives. The substituted chloroisochromans were prepared from
the corresponding methyl acetals and used directly without purification
in a one-pot, two-stage procedure. Saponification of ester 9a provided
the corresponding carboxylic acid, which was found to be levorotatory,
and therefore assigned as the S-enantiomer by comparison to previously
published data.14 Symmetric tetrasubstituted silyl ketene acetals afforded
addition products with uniformly high enantioselectivities (Figure 1). When
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The successful enantioselective catalysis of silyl ketene acetal
addition to racemic 1-chloroisochromans raises interesting mechanistic
questions. The products are isolated in >50% yield in good-to-excellent
ee’s that were found to remain constant over the course of the reaction.
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(17) Similar reactivity and slightly diminished enantioselectivity is observed using
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(19) Preliminary results obtained in additions to both simple and stereochemically
complex tetrahydropyranyl derivatives are included in the Supporting Information.
JA801514M
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