Gram-Scale Strecker Synthesis of Unnatural α-Amino Acids

Significance

The authors report a scalable Strecker synthesis of unnatural amino acids, using a thiourea catalyst (4) and KCN as cyanide source. The catalyst 4 is simplified from their first generation thiourea catalysts 5 which contain a diamino-cyclohexane moiety. In the presence of 0.5 mol% of 4, two equivalents of KCN and 1.2 equivalents of AcOH at 0 ˚C, different aliphatic imines undergo a modified Strecker reaction with high enantioselectivity. The reaction conditions are mild and practical (without purification by chromatography), and 25-100 mmol scale reactions were exemplified for the preparation of 3a-c.

Review: For a review on organocatalytic Strecker reactions, see: P. Merino, E. Marqués-López, T. Tejero, R. P. Herrera Tetrahedron 2009, 65, 1219-1234.