Abstract
Unprecedented phosphine-catalyzed [4+1] cycloadditions of allenyl imides have been discovered using various N-based substrates including methyl ketimines, enamines, and a primary amine. These transformations provide a one-pot access to cyclopentenoyl enamines and imines, or (chiral) γ-lactams through two geminal C-C bond or two C-N bond formations, respectively. Several P-based key intermediates including a 1,4-(bis)electrophilic α,β-unsaturated ketenyl phosphonium species have been detected by 31 P NMR and HRMS analyses, which shed light on the postulated catalytic cycle. The synthetic utility of this new chemistry has been demonstrated through a gram-scaling up of the catalytic reaction as well as regioselective hydrogenation and double condensation to form cyclopentanoyl enamines and fused pyrazole building blocks, respectively.
Highlights
Nucleophilic catalysis, e.g. the conjugate addition of a phosphine or an amine catalyst across electrophilic allenes to generate reactive zwitterionic intermediates, has emerged as an indispensable method for the synthesis of both carbocycles and heterocyles.[1]
Further exploiting allenyl imides in phosphine catalysis are based on the following observations and anticipations: (1) we previously found that the 2-oxazolidinyl group of an α,β-alkenyl imide was readily detached when exposed to nucleophiles (Scheme 2a);[12] (2) a common approach to ketenes is base-mediated elimination of HCl from acyl chlorides (Scheme 2b);[13] (3) upon reaction of allenyl imide 1 with a nucleophilic phosphine catalyst, nucleophilic zwitterionic intermediate E is initially formed via conjugate addition; the elimination of the 2-oxazolidinyl group may result in the generation of the intriguing α,β-unsaturated ketenyl phosphonium intermediate F; the latter may act as a 1,4-(bis)electrophile and trigger unprecedented annulations (Scheme 2c)
It is noted that the synthetic utility of 1,4-(bis)electrophilic intermediates generated via phosphine-induced elimination of an acetate group from β'-acetoxy allenyl esters has been reported by Tong,[14] Fu,[15] and Lu;[16] to the best of our knowledge, the use of imines as reaction partners in this context is unprecedented
Summary
Nucleophilic catalysis, e.g. the conjugate addition of a phosphine or an amine catalyst across electrophilic allenes to generate reactive zwitterionic intermediates, has emerged as an indispensable method for the synthesis of both carbocycles and heterocyles.[1]. It is noted that the synthetic utility of 1,4-(bis)electrophilic intermediates generated via phosphine-induced elimination of an acetate group from β'-acetoxy allenyl esters has been reported by Tong,[14] Fu,[15] and Lu;[16] to the best of our knowledge, the use of imines as reaction partners in this context is unprecedented.
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