Premium
Synthesis of Nonproteinogenic ( R )‐ or ( S )‐Amino Acids Analogues of Phenylalanine, Isotopically Labelled and Cyclic Amino Acids from tert ‐Butyl 2‐( tert ‐Butyl)‐3‐methyl‐4‐oxo‐1‐imidazolidinecarboxylate (Boc‐BMI)
Author(s) -
Seebach Dieter,
Dziadulewicz Edward,
Behrendt Linda,
Cantoreggi Sergio,
Fitzi Robert
Publication year - 1989
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.198919890293
Subject(s) - chemistry , amino acid , pyrrolidine , enantiomer , deprotonation , protonation , lithium diisopropylamide , phenylalanine , medicinal chemistry , enantiomeric excess , stereochemistry , enantioselective synthesis , organic chemistry , catalysis , ion , biochemistry
The enantiomerically pure glycine derivatives ( R )‐ and ( S )‐Boc‐BMI, commercially available on a kg scale, are used as starting materials (Scheme 1) for the preparation of (i) open‐chain amino acids such as α‐deuterio amino acids ( 4, 5 ), β‐arylalanines ( 2 ), aspartic acid derivatives ( 6, 7a, 8 ), or ω‐halo amino acids ( 7b, c, 12, 13, 16, 17, 19, 22 ), (ii) of α‐aminocycloalkanecarboxylic acids ( 9, 11 ), and (iii) of heterocyclic α‐amino acids ( 14, 15, 18, 20 ) containing azetidine, pyrrolidine, piperidine or perhydroazepine rings. Inversion by deprotonation / protonation or deuteration allows to prepare either enantiomer of an amino acid from the same Boc‐BMI enantiomer (Scheme 5). Effects of additives such as the cyclic urea DMPU, lithium salts, or secondary amines upon the reactivity of lithium enolates are discussed and, in part, exploited.