A General Chemoenzymatic Synthesis of Enantiopure cis β-Amino Alcohols from Microbially Derived cis-Glycols

Enantiomerically pure cis -glycols, derived through the microbial metabolism of hydrocarbons, represent a valuable chiral pool for the synthesis of cis β -amino alcohols. One generally applicable route to these important chiral intermediates is described. Reaction of the metabolically formed diol with α -acetoxyisobutyryl chloride affords regioand stereoselectively a single trans -1,2-chlorohydrin acetate isomer. Displacement of chloride by azide, aminolysis of the ester and reduction of the azide provides the requisite amino alcohols. This 4-step route is highly efficient and affords the cis β -amino alcohol enantiomers in 41–57% overall yields. Using the highly enantiopure amino alcohols diastereomeric oxazaborolidines were prepared with both (–)-( S )and (+)-( R )-[2-(1-methoxyethyl)phenyl]boronic acids. As described herein, these derivatives are potentially useful for absolute configurational assignments to cis amino alcohols.