Stereoselective Mn-mediated coupling of functionalized iodides and hydrazones: a synthetic entry to the tubulysin gamma-amino acids.

[structure: see text] Synthesis of gamma-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 alpha-branched amines. Reductive N-N bond cleavage and alcohol oxidation provides alpha-substituted gamma-amino acid building blocks for tubulysin D.