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

The 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′)‐CH 2 CONH‐CH(5′)(Et)), arc described. Their fully protected derivatives 35a and 35b , respectively, are suitable for incorporation into antisense oligonucleotides. Unexpectedly, an attempted Pd II ‐catalysed aza‐ Claisen rearrangement of trichloroacetimidate 7 provided the diastereoisomerically pure cyclopropane derivative 17 , whose structure was confirmed by X‐ray analysis.