Spirocyclic restriction of nucleosides. Synthesis of the first exemplary syn-1-oxaspiro[4.4]nonanyl member.

[reaction: see text] The potential benefits associated with the spirocyclic restriction of nucleosides are summarized. Following exploration of a pi-allylpalladium route to 5'-alpha- or syn-dideoxy examples, we evaluated MOM protection of the 5'-hydroxyl as being suited to the synthesis of the first member of this new class of nucleoside mimic.

1-Oxaspiro[4.4]nonan-6-ones. Synthetic access via oxonium ion technology, optical resolution, and conversion into enantiopure spirocyclic alpha,beta-butenolides.

A general approach to the synthesis of enantiomerically pure spirocyclic alpha,beta-butenolides is presented where the fundamental framework is rapidly elaborated by acid- or bromonium ion-induced rearrangement of the carbinol derived by addition of 2-lithio-4,5-dihydrofuran to cyclobutanone. Subsequent resolution of the resulting ketones by either sulfoximine or mandelate acetal technology has been applied effectively. The availability of these building blocks makes possible in turn the acquisition of the enantiomers of dihydrofurans typified by 17, 35, and 38 and lactones such as 25 and 31, as well as the targeted title compounds. Complementary reductions of the early intermediates provide the added advantage that the alpha- and beta-stereoisomeric carbinol series can be obtained on demand. These capabilities have been coordinated to allow the crafting of any member of the series in relatively few steps.