109 / 2023-10-06 21:44:44

Phosphine-Catalyzed Stereoselective Ring-Opening Addition of Cyclopropenones with Nucleophiles

phosphine-catalyzed;,α-ketenyl phosphorus ylide;,E-selectivity

Phosphorus in Synthetic Chemistry > 1) Phosphorus compounds as catalysts

A phosphine-catalyzed ring-opening addition reaction of cyclopropenones with a variety of nucleophiles (NuH), including oxygen- (phenols, acetophenone oxime, 4-hydroxy-6-methyl-2-pyrone, and N,N-dibenzylhydroxylamine, acetoacetate, acetylacetone, and 1,3-cyclohexanedione, H₂O), nitrogen- (anilines, indole, benzotriazole, and 5-phenyltetrazole, S-prolinol and 4-pyridinol), sulfur- (thiophenols), and carbon-based (malononitrile) ones has been investigated, which produces potentially useful α,β-unsaturated carbonyl derivatives in high yields (up to 99%), with 71 examples, high regioselectivity, and exclusive E-selectivity. The reaction proceeds in high efficiency under very mild conditions using only 1 mol % PPh₃ as the catalyst at room temperature. In additional, thiobenzamide can underwent a cyclization with diphenylcyclopropenone to form 1,3-thiazinone as a pair of diastereomers (dr = 5:1). Unsymmetrical substitution on the two phenyl rings of diphenylcyclopropenone、alkyl and aryl disubstituted cyclopropenones、Mono-substituted cyclopropenone all worked well. The method is also amenable for the synthesis of deuterated alkenes when deuterated nucleophiles (NuD) are employed. The mechanism is investigated by ³¹P NMR monitoring、HMRS experiments and DFT calculations, which suggests an α-ketenyl phosphorus ylide as a key intermediate in the catalytic cycle that captures the nucleophiles in a stereoselective manner and shows that the addition of PhOH would be asynchronous and the attack of PhO⁻ at ketene lag behind the proton transfer. To further illustrate the synthetic usefulness of the reaction, a tandem photocyclization/oxidation process of products was carried out. This organocatalytic ring-opening addition reaction stands in contrast with the transition-metal catalyzed variant, which not only enriches the chemistry of the cyclopropenones but also expands the scope of the phosphine catalysis previously mainly centered on alkenes, alkynes, or allenes. Investigations on the application of this ring-opening addition reaction, especially for the polymer synthesis, are currently underway in our laboratory.