Science and Mathematics Faculty Publications

Access to Oxetane-containing psico-Nucleosides from 2-Methyleneoxetanes: A Role for Neighboring Group Participation?

Document Type

Article

Publication Date

10-26-2011

Journal Title

The Journal of Organic Chemistry

Volume

76

Issue

24

First Page

9962

Last Page

9974

Abstract

The first psico-oxetanocin analog of the powerful antiviral natural product, oxetanocin A, has been readily synthesized from cis-2-butene-1,4-diol. Key 2-methyleneoxetane precursors were derived from beta-lactones prepared by the carbonylation of epoxides. F+-Mediated nucleobase incorporation provided the corresponding nucleosides in good yield but with low diastereoselectivity. Surprisingly, attempted exploitation of anchimeric assistance to increase the selectivity was not fruitful. A range of 2-methyleneoxetane and related 2-methylenetetrahydrofuran substrates was prepared to explore the basis for this. With one exception, these substrates also showed little stereoselectivity in nucleobase incorporation. Computational studies were undertaken to examine if neighboring group participation involving fused [4.2.0] intermediates is favorable.

Keywords

Chemistry

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