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α‐Methylidene‐ and α‐Alkylidene‐β‐lactams from Nonproteinogenic Amino Acids
Author(s) -
Buchholz Rainer,
Hoffmann H. Martin R.
Publication year - 1991
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19910740608
Subject(s) - chemistry , nucleophile , hydrolysis , amine gas treating , ether , solvent , medicinal chemistry , stereochemistry , organic chemistry , catalysis
Treatment of methyl 2‐(1‐hydroxyalkyl)prop‐2‐enoates 1 with conc. HBr solution afforded methyl ( Z )‐2‐(bromomethyl)alk‐2‐enoates 2 , which were transformed regioselectively into N ‐substituted methyl ( E )‐2‐ (aminomethyl)alk‐2‐enoates 3 (S N 2 reaction) and into N ‐substituted methyl 2‐(1‐aminoalkyl)prop‐2‐enoates 4 (S N 2′ reaction). Regiocontrol of nucleophilic attack by amine was accomplished simply by choice of solvent, the S N 2 reaction occurring in MeCN and the S N 2′ reaction in petroleum ether. Hydrolysis and lactamization afforded β‐lactams 7 and 8 , containing an exocyciic alkylidene and methylidene group at C(3), respectively.