Stereoselective Mn-mediated coupling of functionalized iodides and hydrazones: A synthetic entry to the tubulysin γ-amino acids

Abstract

(Chemical Equation Presented) Synthesis of γ-amino acids, important building blocks in bioorganic and natural product chemistry, is accomplished using a stereoselective carbon-carbon bond construction of the chiral amine. Alkyl iodides and chiral hydrazones with protected alcohol functionality are coupled via highly diastereoselective photolytic Mn-mediated addition to the C=N bond, providing access to enantiomerically pure multifunctional chiral α-branched amines. Reductive N-N bond cleavage and alcohol oxidation provides α-substituted γ-amino acid building blocks for tubulysin D.