Conformational Preferences of Allene Ketones in Lewis Base Catalysis: Synthesis of 4H-Pyrans and 3,4-Dihydro-2H-pyrans via α-Regioselective [4+2] Annulations of γ-Substituted Allene Ketones and Activated Alkenes

A Lewis base-catalyzed exclusively alpha-regioselective [4+2] annulation of gamma-substituted allene ketones with 2-arylidene-1,3-indanediones to construct highly functionalized 3,4-dihydro-2H-pyran isomers have been developed. The annulation reaction initiates with addition of NR3/PR3 to s-cis- or s-trans-allene ketone to generate two geometrically distinct zwitterionic isomers, and the ratio of the two zwitterionic isomers depends on catalyst-controlled conformation preference of s-cis/s-trans-allene ketone. By utilizing cinchonine as the catalyst, s-trans-allene ketone usually leads to preferential formation of (3S, 4S)-3-benzoyl-4-phenyl-3,4-dihydro-2H-pyran isomer 3. In contrast, s-cis-allene ketone mainly favors the formation of (3R, 4S)-3-benzoyl-4-phenyl-3,4-dihydro-2H-pyran isomer 5 under the catalysis of R,S-Josiphos-1. It's worth noting that only (3S, 4S)-3-benzoyl-4-phenyl-3,4-dihydro-2H-pyran half-chair isomer 3 can easily isomerize into 4H-pyran. Density functional theory calculations elucidated the origin of considerable difference in isomerization between isomer 3 and isomer 5.

Automated summary

An exclusive alpha-selective annulation reaction between gamma-substituted allene ketones and 2-arylidene-1,3-indanediones catalyzed by Lewis bases has been developed to construct highly functionalized 3,4-dihydro-2H-pyran isomers. The reaction pathway and selectivity are determined by the catalyst-controlled conformation preference of the allene ketones.