Synthesis of functionalized 1,4-cyclohexadienes through intramolecular anionic dearomatization of N-alkyl-N-benzyldiphenylphosphinamides. Insight into the reaction mechanism.
A generalization of the intramolecular nucleophilic dearomatization-electrophilic alkylation reactions of N-alkyl-N-benzyldiphenylphosphinamide anions is presented. The process has been optimized by analyzing the effects of metalation and quench times, additives, the nature of the electrophiles used (MeI, CF(3)SO(3)Me, Me(3)O(+)BF(4)(-), AllylBr, PhCH(2)Br, BrCH(2)CO(2)Me, and RCH=O, where R = Ph, 4-Cl-C(6)H(4), 4-MeO-C(6)H(4), and (i)()Pr), and the alkyl substituent linked to the nitrogen of the phosphinamide. Both HMPA and DMPU act as catalysts. The latter proved to be much more efficient for obtaining high yields of substituted tetrahydrobenzo[c][1,2]-1lambda(5)-phospholes containing a 1,4-cyclohexadiene system with very high regio- and diastereoselectivity. Steric effects in the neighborhood of the benzylic anion tend to decrease the stereoselectivity of the anionic cyclization. The optimization study also served to shed light on the reaction mechanism of the dearomatization process by identifying several intermediate species and showing the reversibility of the anionic cyclization step as well as of the reaction with aldehydes.
Fernández
Ignacio
I
Area de Química Orgánica, Universidad de Almería, Carretera de Sacramento, Spain.
Forcén-Acebal
Angela
A
García-Granda
Santiago
S
López-Ortiz
Fernando
F