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EPC‐Synthesis of β‐Amino Acid Derivatives through Lithiated Hydropyrimidines
Author(s) -
Seebach Dieter,
Boog Alois,
Schweizer W. Bernd
Publication year - 1999
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/(sici)1099-0690(199901)1999:1<335::aid-ejoc335>3.0.co;2-a
Subject(s) - chemistry , enantiopure drug , stereocenter , electrophile , propargyl , deprotonation , hydrolysis , nuclear magnetic resonance spectroscopy , stereochemistry , organic chemistry , medicinal chemistry , enantioselective synthesis , ion , catalysis
Racemic and enantiopure 2‐ tert ‐butyltetrahydropyrimidinones (from pivalaldehyde and 3‐aminocarboxylic acids) are converted to Alloc‐, Boc‐, and Z‐protected cyclic imino esters ( 7 – 10 , Schemes 2–4). These are deprotonated to Li enaminates ( K , L ). Reactions with electrophiles ( prim. , sec . alkyl, allyl, benzyl, propargyl halides, aldehydes, imines, enoates) give good yields and are highly diastereoselective (products 11 – 42, Schemes 5–10). A two‐step cleavage (removal of protecting group and hydrolysis) under very mild conditions converts the heterocyclic products to α‐branched β‐amino acid methyl esters ( 43 – 61 , Schemes 11–13). The structure of the products is determined by NMR spectroscopy (Figure 1), by chemical correlation (Scheme 14), and by X‐ray analysis (Figure 2, 3, 7, Table 1). A structure of the Li enaminates is proposed (Figure 4). Mechanistic models are derived for the reactions occurring with formation of two stereogenic centers with relative topicity like (Figures 5, 6).