Reduction of 4-oxo α-amino acids as a route to 4-hydroxylated α-amino acids. Concise approaches to the synthesis of clavalanine, erythro-4-hydroxyornithine and (+)-bulgecinine

Abstract

The stereochemical course of reduction of derivatives of 4-oxo α-amino acids 3 to give cis- and trans-γ-substituted α-aminobutano-4-lactones 9 and 10 using a range of hydride reducing agents is reported. Although reduction with sodium boranuide (sodium borohydride) in protic solvents proceeds with low stereoselectivity, use of triethylsilane–boron trifluoride–diethyl ether gives good selectivity in favour of the cis-isomer, provided that the 4-substituent is phenyl. Moderate to excellent stereoselectivity in favour of the trans-isomer may be obtained by using L-Selectride® in tetrahydrofuran. The presence of an additional stereogenic centre at C-5 completely overwhelms the effect of the α-centre. Applications of this method in approaches to the synthesis of clavalanine, erythro-4-hydroxyornithine and (+)-bulgecinine are described.