65484-48-2Relevant academic research and scientific papers
Asymmetric Syntheses via Heterocyclic Intermediates, IV. - Asymmetric Synthesis of α-Methylphenylalanine and its Analogues by Alkylation of 1-chiral Substituted 4-Methyl-2-imidazoline-5-one
Schoellkopf, Ulrich,Hausberg, Hans-Heinrich,Segal, Marcos,Reiter, Udo,Hoppe, Inga,et al.
, p. 439 - 458 (2007/10/02)
Treatment of 2-isocyano-N-propionamide (3a) with butyllithium or potassium tert-butoxide (-70 deg C, tetrahydrofuran) initially causes metalation and subsequent (at ca. -20 deg C) cyclization to give the anionized 4-methyl-1--2-imidazolin-5-one (8).This reacts with benzyl or heterobenzyl halides to yield (4S)-4-benzyl- or (4S)-4-heterobenzyl-4-methyl-1--2-imidazolin-5-ones 9 with an asymmetric induction (d.e. = diastereomeric excess) >>95percent.Hydrolysis of 9 gives α-methylphenylalanine or its analogues of type 11 (nearly optically pure) which have been characterized as their N-acetyl derivatives 12.More over, (S)-1-phenylethylamine (2a), the chiral auxiliary compound, is recovered. - With non-benzylic alkyl halides d.e. is much lower (i.e. with allyl bromide 17percent, with cyclohexylmethyl iodide 35percent). - A model concept for the asymmetric induction which also explains the extremely high asymmetric induction with benzyl halides is proposed. - Methods for the synthesis of 2- unsubstituted 4-alkyl-2-imidazolin-5-ones (type 9a, 15-17) and 2-substituted 4-alkyl-2-imidazolin-5-ones (type 18-20) are described. - The X-ray analysis of 4-benzyl-4-methyl-1-(1'-phenylethyl)-2-imidazolin-5-one (9b) shows a) the "phenyl inside conformation" (folded conformation) for the C-4-benzyl group and b) C-1' fixed in such a way that the hydrogen atom of the phenylethyl group lies in the heterocyclic plane, pointing towards the carbonyl oxygen.
