3-fluoro-6-tert-butyltetrahydropyranosyl trichloroacetamidates. "chiral auxiliary donors" for hydroxyalkyl radicals.

An improved THP-based chiral auxiliary for hydroxyalkyl radicals is reported. The key modifications involve introduction of a fluorine substituent at C-3 to make the acetal center more robust and the use of Schmidt's trichloroacetamidate glycosylation methodology for efficient attachment of the auxiliary to the radical precursor. The resulting chiral hydroxyalkyl radical equivalents add to methyl 2-trifluoroacetoxyacrylate with selectivities ranging from 9:1 (0 degrees C) to 15:1 (-78 degrees C).

Benzaldehyde lyase-catalyzed enantioselective carboligation of aromatic aldehydes with mono- and dimethoxy acetaldehyde.

[reaction: see text] Benzaldehyde lyase from the Pseudomonas fluorescens catalyzes the reaction of aromatic aldehydes with methoxy and dimethoxy acetaldehyde and furnishes (R)-2-hydroxy-3-methoxy-1-arylpropan-1-one and (R)-2-hydroxy-3,3-dimethoxy-1-arylpropan-1-one in high yields and enantiomeric excess via acyloin linkage. Aromatic aldehydes and benzoins are converted into enamine-carbanion-like intermediates prior to carboligation.

A new and efficient chemoenzymatic route to both enantiomers of 4-hydroxycyclohex-2-en-1-one.

[reaction: see text] A chemoenzymatic synthesis of both enantiomers of the pharmacologically interesting 4-hydroxycyclohex-2-en-1-one in three steps starting from 3-methoxycyclohex-2-en-1-one is described. Manganese(III) acetate-mediated acetoxylation followed by enzyme-mediated hydrolysis of alpha-acetoxy enone affords acetoxy enone 3 and hydroxy enone 4 with high enantiomeric excesses and in good yields. The reduction of the acetoxy and hydroxy enones furnished both enantiomers of 4-hydroxycyclohex-2-en-1-one in high enantiomeric excess.