Synthesis of [1α,2β,3α-2,3-bis(benzyloxymethyl)cyclobutyl]imidazol-5-amines: important precursors to cyclobut-A derivatives

Abstract

A comparative study has been carried out on two different reaction sequences starting either from Feist's acid or ketene diethyl ketal and diethyl fumarate to prepare protected derivatives of (1α,2β,3α)-2,3-dihydroxycyclobutylamine. Difficulties were experienced upon reaction of the tert-butyldimethylsilyl-protected amine 13a with ethyl (Z)-N-(2-amino-l,2-dicyanovinyl)formimidate 6, but the dibenzoyl derivative 13b reacted smoothly to give the amidine 19 in high yield. The amidine is a useful intermediate for the synthesis of cyclobutane-based carbocyclic nucleosides. It can be readily converted by base treatment into the 4-cyanoimidazol-5-amine derivative 4b; a precursor to the dibenzoyl derivative of racemic Cyclobut-A and a new 1-amino-6-iminopurine derivative 25. Treatment of compound 19 with a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) afforded the previously unknown 5-amino-4-(cyanoformimidoyl)imidazole derivative 20. This has been used to synthesize new 1,2-dihydropurine and 1-methyl derivatives of Cyclobut-A in good yields.