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Highly Stereoselective Strecker Synthesis Induced by a Slight Modification of Benzhydrylamine from Achiral to Chiral
Author(s) -
Takamatsu Naoya,
Aiba Shohei,
Yamada Takuya,
Tokunaga Yuji,
Kawasaki Tsuneomi
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201704033
Subject(s) - stereoselectivity , strecker amino acid synthesis , diastereomer , chirality (physics) , chemistry , chiral auxiliary , amine gas treating , enantioselective synthesis , stereochemistry , combinatorial chemistry , organic chemistry , catalysis , chiral symmetry , nambu–jona lasinio model , physics , quantum mechanics , quark
2‐Methylbenzhydrylamine is a chiral variant of achiral benzhydrylamine; however, the chirality formed from the small difference between the phenyl and o ‐tolyl groups is not expected to induce sufficient stereoselectivity in conventional homogeneous reactions. Initiated by the spontaneous formation and asymmetric amplification of the enantioenriched N ‐benzhydryl‐α‐aminonitrile forming conglomerate, we here report that ( S )‐ and ( R )‐configured title amine, upon the Strecker reaction with achiral aldehydes and HCN, afford the corresponding α‐aminonitriles with up to >99.5 % diastereomeric excess, in conjunction with an enhancement of chirality in the solid state. l ‐Alanine with 98 % ee was synthesized from the ( S )‐amine by using the method discussed here. Achiral aromatic and heteroaromatic aldehydes could also be successfully utilized to afford chiral α‐aminonitriles in a highly stereoselective manner. The stereodivergent synthesis of styrylglycine nitriles has also been accomplished by using racemic and enantioenriched 2‐methylbenzhydrylamine. Thus, accompanied with a small rearrangement of the common substrate from achiral toward chiral, the present reactions induce an enhancement of chirality, and expands the concept of stereoselective synthesis to increase the opportunity to access highly enantioenriched compounds such as α‐amino acids.