Amphiphilic allylation of arylidene-1,3-oxazol-5(4H)-one using bis-pi-allylpalladium complexes: an approach to synthesis of cyclohexyl and cyclohexenyl alpha-amino acids

作者：Genady Afaf R; Nakamura Hiroyuki^*

来源：Organic and Biomolecular Chemistry, 2011, 9(20): 7180-7189.

DOI：10.1039/c1ob05952a

An efficient method for synthesis of cyclohexyl and cyclohexenyl alpha-amino acids via palladium-catalyzed three-component assemblies followed by ring-closing metathesis (RCM) is described. The present catalytic reaction is successfully extended to substituted benzylidene azlactones 2a-j RCH=(1,3-oxazole): R = alkyl or aryl. The amphiphilic bis-allylation of these substrates has been achieved by replacing toxic allylstannanes with allyltrifluoroborate and the reaction proceeded smoothly to afford the corresponding 1,7-diene derivatives 3a-j in acceptable to good yields. RCM of the resulting octadienes using the first generation Grubbs catalyst gave easy access to stereodefined substituted cyclohexene derivatives 7-11 in high yields. Acid hydrolysis of the oxazolone ring of 7-10 gave protected amino acids 12-16. Debenzoylation of 13 and 15 afforded 1-amino-6-arylcyclohex-3-enecarboxylic acids 17 and 18 in excellent yields, respectively. Moreover, catalytic reduction of 13 gave the corresponding cyclohexane derivative 19 which could be debenzoylated to give 1-amino-2-phenylcyclohexene-1-carboxylic acid (20). The structures of compounds 9, 12 and 13 were confirmed by X-ray structural analysis. It is an excellent method for creating a wide range of cyclic alpha,alpha-disubstituted alpha-amino acids.

• 出版日期2011