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Synthesis of Nonracemic α‐Trifluoromethyl α‐Amino Acids from Sulfinimines of Trifluoropyruvate
Author(s) -
Asensio Amparo,
Bravo Pierfrancesco,
Crucianelli Marcello,
Farina Alessandra,
Fustero Santos,
Soler Juan García,
Meille Stefano V.,
Panzeri Walter,
Viani Fiorenza,
Volonterio Alessandro,
Zanda Matteo
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200104)2001:8<1449::aid-ejoc1449>3.0.co;2-2
Subject(s) - chemistry , diastereomer , steric effects , trifluoromethyl , stereoselectivity , chiral auxiliary , alkyl , reagent , stereochemistry , organic chemistry , medicinal chemistry , enantioselective synthesis , catalysis
We describe a novel and useful method for the synthesis of nonracemic α‐trifluoromethyl α‐amino acids (α‐Tfm‐AAs). Key building blocks are the sulfinimines ( S )‐ 1a and ( S )‐ 1b , prepared by Staudinger reaction from trifluoropyruvate esters and the chiral N ‐sulfinyl iminophosphorane ( S )‐ 8 , which were treated with benzyl, allyl, and alkylmagnesium halides. The resulting diastereomeric N ‐sulfinyl α‐Tfm α‐amino esters, 12 and 13 , were produced with moderate to good stereoselectivity and yields. When alkyl Grignard reagents were used, stereocontrol became progressively higher with increasing steric bulk, while reversed, though poor, stereocontrol was achieved with benzyl/allyl Grignard reagents. An explanation for the observed stereochemical outcome is proposed, on the basis of the exclusive E geometry ( N ‐sulfinyl and CF 3 trans about the C=N bond) of the chiral sulfinimines 1 . This assignment is the product of structural correlation and is supported by ab initio calculations and NOE experiments. Sulfinamides 12 and 13 were transformed into a series of nonracemic α‐Tfm‐AAs 16−22 . The sulfinyl auxiliary can be regenerated and recycled.