1239987-75-7Relevant academic research and scientific papers
Versatile access to 2-aminocyclobutene-1-carboxylic acid derivatives and their incorporation into small peptides
De Meijere, Armin,Limbach, Michael,Janssen, Andre,Lygin, Alexander,Korotkov, Vadim S.
experimental part, p. 3665 - 3671 (2010/08/22)
Under a newly developed set of mild conditions [EtN(iPr)2, LiI, DMF, 20 °C, 3 d], methyl 2-chloro-2-cyclopropylideneacetate (1) smoothly undergoes Michael addition of various benzylamines (4 examples) with ensuing ring enlargement and elimination to give in very good yields (81-99%) the correspondingly substituted methyl 2-(benz-ylammojcyclobutenecarboxylates 3a-d, which were subsequently converted into the N-Boc-protected derivatives 4a-d. After hydrolysis of the esters, the free β-amino acids 5a, b were cleanly condensed with the methyl esters of glycine, (S)-proline, (S)-phenylglycine and (S)-tryptophan to give the dipeptides 6a-8a, 9b in 58-89% yield. The cyclic dipeptides 15e,f, consisting of a 2-aminocyclobutenecarboxylic acid and a glycine fragment, were obtained in 38 and 45 % yield, respectively, upon treatment of the spirocyclopropanated chlorohexahydrodiazepinediones 10e,f with sodium cyanide in DMSO at elevated temperatures. Palladium-catalyzed hydrogenation of 4a afforded, methyl N-Boc-2-aminocyclobutanecarboxylate 19 as a mixture of cis and trons isomers.
