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

Abstract

A Lewis base-catalyzed exclusively α-regioselective [4 + 2] annulation of γ-substituted allene ketones with 2arylidene-1,3-indanediones to construct highly functionalized 3,4-dihydro-2H-pyran isomers have been developed. The annulation reaction initiates with addition of NR 3 /PR 3 to s-cisor 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-3,4dihydro-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-4phenyl-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.

Highlighting the Rich Chemistry of the Allenone Moiety

“…[187,188] Interestingly, a change of regioselectivity has been observed when quinine has been used as catalyst, obtaining adducts 390 from the reaction of pyrazolones with the inner double bond of the allene moiety of allenones 2 lacking substitution at the internal carbon atom (Scheme 69a). [187,188] Alternative fused pyran structures have been synthesized from allenones and different oxadienes such as benzylidene-1H-indene-1,3(2H)-diones 391 [189] and 2,3-dioxopyrrolidine derivatives 394. [190] In both examples, cinchonine derived alkaloids 392 and 395 have been used as catalysts, providing compounds 393 and 396 in a regioselective manner (Schemes 69b and 69c).…”