A diastereoselective radical cyclization approach to substituted quinuclidines.
A new, concise, and flexible approach to novel quinuclidines has been developed, which employs a phosphorus hydride mediated radical addition/cyclization reaction in the key step. 1,7-Diene 5 reacts with diethyl thiophosphite in an efficient and diastereoselective radical addition/cyclization reaction to give trisubstituted piperidines 4ab. Piperidines 4ab are subsequently converted into 2,5-disubstituted quinuclidines using S(N)2-type cyclizations. Finally, the resulting quinuclidines are shown to undergo novel Horner-Wadsworth-Emmons-type (HWE-type) reactions to give unsaturated quinuclidines 21a and 21b, which have structures similar to that of (-)-quinine 1.
Hunt
Thomas A
TA
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.
Parsons
Andrew F
AF
Pratt
Robert
R
D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D011812:Quinuclidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D005609:Free Radicals; D011812:Quinuclidines