C O MMU N I C A T I O N S
Table 2. Mg-Catalyzed anti-Aldol Reactions of 1a with
Representative Aldehydes (Eq 4)
workup afforded 9 in 87% isolated yield of the major diastereomer
a
(eq 6). Optimized conditions for this family of substrates include
the use of MgBr ‚OEt . Chemical correlation with known material
2
2
showed that 9 is the opposite anti-aldol diastereomer to that seen
in the oxazolidinone series (eq 4).16 Propiophenone readily under-
goes the magnesium-catalyzed aldol reaction with benzaldehyde,
affording 90% yield and 95:5 anti:syn diastereomeric ratio (eq 7).
Further investigations into the mechanism and catalytic enantio-
selective variants of this process are currently underway and results
will be reported in due course.
Acknowledgment. Support has been provided by the NSF and
the NIH (GM 33328-18). We acknowledge Dr. Paul Reider (Merck)
for the suggestion of ethyl acetate as a reaction solvent on the basis
of practical considerations. J.T.S. gratefully acknowledges an NIH
Postdoctoral Fellowship.
a
Procedure A: reactions were conducted with 1.0 equiv 1, 0.2 equiv
MgCl2, 2.0 equiv of triethylamine, 1.5 equiv of TMSCl, 1.2 equiv of RCHO
at 0.5 M in EtOAc for 24 h. Procedure B: reaction conducted as in
Procedure A but with 0.1 equiv MgCl2 and the addition of 0.3 equiv of
NaSbF6 at 0.2 M in ethyl acetate. Table 1 footnote b. Isolated yield of
a single diastereomer.
Supporting Information Available: Experimental procedures,
spectral data for all compounds, crystallographic data, and stereochem-
ical proofs (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
b
c
b
aldolate silylation is therefore essential for achieving a catalytic
process. We have also carried out experiments that bear on the
issue of product silylation and retro-aldolization (eq 5). In conjunc-
tion with this trapping experiment it was determined that p-
tolualdehyde reacts under the indicated conditions twice as fast as
p-methoxybenzaldehyde in a direct competition experiment. In the
illustrated reaction, the diastereomerically pure aldol adduct 5b
References
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1
7% yield. The diastereomer ratios within each family of aldol
2
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(
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(
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(
(
(
(
(
(
(
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be inferior in either diastereoselectivity or yield.
12) Magnesium halides were found to be superior to other metal halides
4 3 3 2 2
examined (TiCl , AlCl , ScCl , ZnCl , MnI ).
2 2
13) Aliphatic aldehydes (i-PrCHO, t-BuCHO, PhCH CH CHO) suffer from
low conversion.
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Chiral acylthiazolidinethiones have also been reported as useful
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major diastereomer different from the corresponding oxazolidinone
case.15 Magnesium-catalyzed aldol reaction of chiral acylthiazoli-
1
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