Silyl Ethers Containing the Radical Acceptor

Previous examples of silyl-tethered radical cyclizations have involved the incorporation of the radical precursor during the formation of the silyl ether tether. An alternative would be to incorporate the radical acceptor. A number of suitable silyl chlorides are commercially available which facilitate the preparation of such cyclization precursors. 

C-branched nucleosides have been found to possess a number of biological properties, including antibacterial, antitumour, and antiviral activity. This has fueled a drive for preparing novel analogs of such molecules. Chattopadhyaya and co-workers have published extensively on the manipulation of nucleosides using intramolecular radical cyclizations [76], which are carried out under mild and, importantly, neutral conditions, making them compatible with a range of functionality. 

The same group have also investigated the incorporation of the radical acceptor moiety via a silyl ether tether [76b]. A phenylseleno substituent was stereospecifically incorporated into either the 2 - or 3 -position of four thymidine nucleosides, followed by incorporation of an olefinic radical acceptor into the vicinal hydroxyl group by reaction with (allyl)dimethy]silyl chloride. In all cases, only produets resulting from a 1-endo cyclization mode were isolated after treatment with Bu3SnH/AIBN. 

Chattopadhyaya and co-workers have also demonstrated that alkynyl groups can be used as radical acceptors when linked through a silyl ether [76c]. Radical cyclization and subsequent oxidative cleavage of the tether provided access to 2 - and 3 -C-branched a-keto-]3-D-ribonucleosides, usually in good to excellent yields. 

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