Aza‐Claisen Rearrangement: Synthesis of 5′‐branched 5′‐aminothymidines

Abstract

AbstractThe syntheses of both diastereoisomers of 5′‐ethyl‐substituted thymidine dimers, the (5′R)‐ and (5′S)‐configurated 33a and 33b respectively, in which the natural phosphodiester linkage is replaced by an amide group (C(3′)‐CH2CONH‐CH(5′)(Et)), arc described. Their fully protected derivatives 35a and 35b, respectively, are suitable for incorporation into antisense oligonucleotides. Unexpectedly, an attempted PdII‐catalysed aza‐Claisen rearrangement of trichloroacetimidate 7 provided the diastereoisomerically pure cyclopropane derivative 17, whose structure was confirmed by X‐ray analysis.