Vinylogous Reactivity of Enol Diazoacetates with Donor–Acceptor Substituted Hydrazones. Synthesis of Substituted Pyrazole Derivatives

Abstract

A regiospecific synthesis of multi-functional pyrazoles has been developed from a cascade process triggered by Rh(II)-catalyzed dinitrogen extrusion from enoldiazoacetates with vinylogous nucleophilic addition followed by Lewis acid catalyzed cyclization and aromatization.

Reversal of the Regiochemistry in the Rhodium‐Catalyzed [4+3] Cycloaddition between Vinyldiazoacetates and Dienes

“…We rationalized that the formation of the regioisomeric [4+3] cycloadduct 13 a was most likely caused by a competing reaction of the diene occurring at the vinylogous position of the carbenoid, thus generating a zwitterionic intermediate, which then cyclizes to 13 a. [7][8][9] Previous studies have shown that vinylogous reactivity is favored in polar solvents. [7] Indeed, when the reaction was repeated using dichloromethane as the solvent, the ratio of 12 a to 13 a improved to 87:13, and the regiosiomeric [4+3] cycloadduct 13 a was produced in 71 % ee.…”

“…Chemie quent cyclization to the cycloheptadiene 25 is faster than bond rotation. Zwitterionic intermediates have been shown to be likely in several types of stereoselective reactions of rhodium vinylcarbenes, [8] so the concept of rapid cyclization of zwitterionic intermediates without epimerization is well established. Both the diene and the vinylcarbenoid would need to react through an s-cis conformation for ring closure to occur without bond rotation.…”

“…In general, vinylogous reactivity under rhodium(II) catalysis is most common when the vinyl terminus of the carbenoid is unsubstituted. [8] [Rh 2 (S-BTPCP) 4 ], however, is capable of inducing vinylogous reactivity on more highly substituted vinylcarbenes. [8j] Therefore, the [Rh 2 (S-BTPCP) 4 ] reaction of the methyl-substituted vinyldiazoacetate 17 was examined ( Table 4).…”

Cycloaddition reactions of enoldiazo compounds

“…Additionally, when donor/acceptor-substituted hydrazones ( N -aryl hydrazonoacetates) were used instead of diarylhydrazones 42 , a series of pyrazole derivatives were formed via dirhodium(II)-catalyzed vinylogous addition followed by Lewis acid-catalyzed cyclization and aromatization. 134 …”

N-vinylation and N-allylation of 3,5-disubstituted pyrazoles by N–H insertion of vinylcarbenoids

“…The vinylogous reactivity of rhodium carbenoids derived from vinyl-diazoacetates, including those without [39,40] and those with [29,32,41,42] a substituent at the vinyl terminus, is known and has been discussed. Among other factors, this vinylogous carbenoid reactivity is favored with bulky substrates and bulky ligands on the rhodium catalyst [29,32], furthermore by the use of diruthenium(I,I) [43] and silver catalysts.…”