Enzymes in Organic Chemistry, 11: [1] Hydrolase‐Catalyzed Resolution of α‐ and β‐Hydroxyphosphonates and Synthesis of Chiral, Non‐Racemic β‐Aminophosphonic Acids

The enantioselective acylation of racemic diisopropyl α‐ and β‐hydroxyphosphonates by hydrolases in t ‐butyl methyl ether with isopropenyl acetate as acyl donor is limited by the narrow substrate specificity of the enzymes. High enantiomeric excesses (up to 99%) were obtained for the acetates of ( S )‐diisopropyl 1‐hydroxy‐(2‐thienyl)methyl‐, 1‐hydroxyethyl‐ and 1‐hydroxyhexylphosphonate and ( R )‐diisopropyl 2‐hydroxypropylphosphonate. The hydrolysis of a variety of β‐chloroacetoxyphosphonates by the lipase from Candida cylindracea and protease subtilisin in a biphasic system gives ( S )‐β‐hydroxyphosphonates (ee 51–92%) enantioselectively. ( S )‐2‐Phenyl‐2‐hydroxyethyl‐ and ( S )‐3‐methyl‐2‐hydroxybutylphosphonates (ee 96% and 99%, respectively) were transformed into ( R )‐2‐aminophosphonic acids of the same ee.