C O M M U N I C A T I O N S
and 6) is possible without loss in efficiency or enantiocontrol (60-
88% yield, 97-99% ee). Notably, these mild reaction conditions
allow the use of electron-rich π-systems which are typically prone
to oxidative degradation. For example, enamine oxidation to access
enantio-enriched R-oxyaldehydes can be selectively accomplished
with substrates that incorporate olefinic or indolic functionality
(entries 4 and 8; g80% yield, g98% ee).
pot procedure highlights the utility of this organocatalytic protocol
as a dihydroxylation surrogate. Specifically, reduction of the
oxyamination product with NaBH4, followed by N-O bond
hydrogenolysis provides the corresponding terminal diol in 74%
yield and 98% ee (eq 4). With respect to operational convenience,
it should be noted that all reactions performed in this study were
conducted in an aerobic atmosphere with wet solvents.
Table 3. Enantioselective R-Oxyamination: Substrate Scope
In summary, we have described the first direct, enantioselective
R-oxyamination of aldehydes. Further efforts to evaluate the scope
of this and related processes are underway. A full account of these
studies will be forthcoming.
Acknowledgment. Financial support was provided by the
NIHGMS (R01 GM66142-01) and kind gifts from Bristol-Myers
Squibb, Johnson and Johnson, Lilly, and Merck Research Labo-
ratories. D.W.C.M is grateful for support from the Sloan Foundation
and Research Corporation. C.J.S. is grateful to the NIH for
postdoctoral fellowship support (NIH-F32-CA-091635-01).
Supporting Information Available: Experimental procedures,
structural proofs, and spectral data for all new compounds (PDF). This
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a Yields based upon isolation of the corresponding primary alcohol.
b Enantiomeric excess determined by chiral HPLC analysis (Chiracel AD).
c Using 2 mol % L-proline. d Using 10 mol % L-proline. e Yield determined
by NMR analysis.
The R-oxyaldehyde products are oligomeric in solution and were
most conveniently isolated as the corresponding primary alcohols.
Nonetheless, these oligomeric aldehydes smoothly undergo reactions
typical of aldehydes. For example, treatment of the unpurified
oxyamination product with dibenzylamine and sodium triacetoxy-
borohydride provides 1,2-amino alcohols in high yield and with
excellent enantioselectivity (eq 3). Furthermore, a convenient one-
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