Phosphine‐Catalyzed [3+2] and [4+3] Annulation Reactions of C,N‐Cyclic Azomethine Imines with Allenoates

Abstract

Phosphine-catalyzed [3+2] and [4+3]annulation reactions of C,N-cyclic azomethine imines with allenoates have been developed to give a variety of pharmaceutically attractive tetrahydroisoquinoline derivatives in moderate to excellent yields. The two distinct reaction pathways, [3+2] and [4+3]cyclization, depend on the nature of the nucleophilic phosphine and the allenoate. Generally, for α-alkylallenoates, the reactions always proceed with [3 +2]cyclization as the major pathway no matter what phosphine was used; for α-ArCH2-substituted allenoates, the reaction pathway was controlled by the phosphine catalyst used.

Organophosphine-Catalyzed [4C+X] Annulations

“…Despite its great efficiency in construction of 5- or 6-membered rings, phosphine-catalyzed preparation of medium-sized rings was elusive until in 2012. Guo, Zhong, Kwon and coworkers described phosphine-catalyzed [3+2] and [4+3] annulation reactions of α-substituted allenoates with C , N -cyclic azomethine imines for the synthesis of a variety of pharmaceutically important tetrahydroisoquinoline derivatives ( Scheme 22 ) [ 60 ]. Interestingly, they found that the nucleophilic phosphine catalyst together with the allenoate substrates had a great influence on the chemoselectivity of the annulation reaction.…”

Hydrazones as substrates for cycloaddition reactions

“…Such azomethine imines are highly reactive and add both to electron-deficient and to electron-rich dipolarophiles. The [3+2]-cycloaddition reactions of C,N-cyclic azomethine imines with alkynes, 183 ± 185 alkenes, 151, 152, 186 ± 188 allenoates, 153,189,190 carbon disulfide and isothiocyanates, 155,191 thioesters and thioketones 192 and isocyanides 193 …”

Diastereodivergent Synthesis of Pyrazoline Derivatives through [3 + 2] Cycloaddition of Baylis–Hillman Adducts and Nitrilimines

“…In contrast, as a readily available dipole, the application of nitrilimines in the cycloaddition of Baylis–Hillman adducts is very unsatisfactory, and only a few specific examples were described . As our continuing efforts on cycloaddition reactions , herein, we present a diastereodivergent [3 + 2] cycloaddition of Baylis–Hillman adducts and nitrilimines generated in situ to synthesize an array of pyrazoline derivatives under mild conditions (Scheme ).…”