The first radical method for the introduction of an ethynyl group using a silicon tether and its application to the synthesis of 2'-deoxy-2'-C-ethynylnucleosides.
A novel radical method for the stereoselective introduction of an ethynyl group has been developed. When a solution of ethynyldimethylsilyl (EDMS) or [2-(trimethylsilyl)ethynyl]dimethylsilyl (TEDMS) ethers of trans-2-iodoindanol was treated with Et(3)B followed by tetrabutylammonium fluoride in toluene, atom transfer 5-exo-cyclization and subsequent elimination occurred to give cis-2-ethynylindanol in high yield. The method was shown to be useful in the introduction of an ethynyl group in various five- and six-membered-ring iodohydrins. Furthermore, 2'-deoxy-2'-C-ethynyluridine (6) and -cytidine (7), which were designed as novel antimetabolites, were readily synthesized by using this method as the key step. This would be the first example in which a radical reaction was used for introducing an ethynyl group.
Sukeda
Makoto
M
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Ichikawa
Satoshi
S
Matsuda
Akira
A
Shuto
Satoshi
S
D002625:Chemistry, Organic / Q000379:methods*; D003500:Cyclization; D007202:Indicators and Reagents; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D012825:Silicon / Q000737:chemistry*; D013237:Stereoisomerism
D007202:Indicators and Reagents; D009705:Nucleosides; D012825:Silicon