Synthesis of Benzofuranones via Malonates Desymmetrization: Yield Increase by the Portion‐wise Addition of Quinones

Abstract

The organocatalyzed addition of several malonates to 1,4-benzoquinones affords benzofuranones bearing a quaternary stereocenter with good enantioselectivity. This reaction is an intramolecular desymmetrization since it proceeds through the formation of an arylated achiral malonate that cyclizes to give the reaction product. The addition rate of the quinone dramatically affects the reaction yield which was originally low. The yield was considerably increased, in some cases, from less than 20 % to over 95 %, by adding the quinone in portions rather than at once, keeping similar enantioselectivity. A possible rationalization for the preferential formation of the indicated enantiomer has been investigated by DFT calculations.

Recent advances towards organocatalytic enantioselective desymmetrizing reactions

“…Consequently, substantial endeavors have been devoted to this burgeoning domain during the last 5 years and a diverse number of novel desymmetric transformations have been successively exploited. Apart from aforementioned cases, other readily available substrates have been studied as well, such as diesters [101], acetals [102], and diamines [103,104]. These remarkable advances not only combine the respective advantages of organocatalysis with desymmetrization, which accelerates the development of related methodologies, but also open up new avenues for synthetic community.…”

Annulations involving p-benzoquinones: stereoselective synthesis of fused, spiro and bridged molecules

“…The organocatalyzed coupling of malonates 66 with benzoquinones 65 affording enantioenriched benzofuranones 68 was reported by Salvio and Bella. 83 Interestingly, the yield of the cyclization reaction could be enhanced via the portion-wise addition of quinones rather than at once, maintaining similar enantioselectivity (up to 95 : 5 er). Differently substituted malonates (R 2 = Me, Et, Bn, n Pr, NHCOMe, etc. )…”

Benzazetidines and Related Compounds: Synthesis and Potential

“…In 2019, Bella, Salvio, and their co‐workers, in the course of their studies about enantioselective organocatalysis, reported an organocatalytic synthesis of benzazetidines starting from inexpensive materials, which does not require any additive based on transition metals, unlike the procedure recently reported and illustrated above . The starting materials of this preparation are isatin and its derivatives.…”