followed by an intramolecular 8-endo-trig radical cyclization. The planar and rigid
molecular scaffold provided by the bicyclic framework in 145 limits the conformational degrees of freedom of the alkyne and alkene side chains so that a highly
and efficient unusual 8-endo vinyl radical cyclization can occur.
This regioselectivity is in line with that found in the existing literature, which
clearly demonstrates the predominance of the 8-endo cyclization mode over the
7-exo mode [128].
Mandal and Roy [129] developed novel titanocene chloride-mediated 8-endo
radical cyclizations (Scheme 31). Through the generation of radicals from epoxides
149 and 151, a cyclization took place to form the eight-membered ring ethers 150
and 152, respectively. The mechanism for the formation of 152 from 151 is
depicted in Scheme 31. Ti(III) reagents reacted as a single electron reductor to
open the epoxide motif in 151 to form intermediate 153, which then underwent an
8-endo radical cyclization to form 154. Radical intermediate 154 was reduced by a
second equivalent of Ti(III) species to form 155, which underwent protonation to
furnish 152.
Scheme 30 Thiophenol-mediated radical cyclization reported by Majumdar et al.
Scheme 31 Radical cyclization reactions reported by Roy et al.
Synthesis of Eight- to Ten-Membered Ring Ethers
345
molecular scaffold provided by the bicyclic framework in 145 limits the conformational degrees of freedom of the alkyne and alkene side chains so that a highly
and efficient unusual 8-endo vinyl radical cyclization can occur.
This regioselectivity is in line with that found in the existing literature, which
clearly demonstrates the predominance of the 8-endo cyclization mode over the
7-exo mode [128].
Mandal and Roy [129] developed novel titanocene chloride-mediated 8-endo
radical cyclizations (Scheme 31). Through the generation of radicals from epoxides
149 and 151, a cyclization took place to form the eight-membered ring ethers 150
and 152, respectively. The mechanism for the formation of 152 from 151 is
depicted in Scheme 31. Ti(III) reagents reacted as a single electron reductor to
open the epoxide motif in 151 to form intermediate 153, which then underwent an
8-endo radical cyclization to form 154. Radical intermediate 154 was reduced by a
second equivalent of Ti(III) species to form 155, which underwent protonation to
furnish 152.
Scheme 30 Thiophenol-mediated radical cyclization reported by Majumdar et al.
Scheme 31 Radical cyclization reactions reported by Roy et al.
Synthesis of Eight- to Ten-Membered Ring Ethers
345