Enantioselective Catalytic [4+1]‐Cyclization of ortho‐Hydroxy‐para‐Quinone Methides with Allenoates

Abstract

The first highly asymmetric catalytic synthesis of densely functionalized dihydrobenzofurans is reported, which starts from ortho ‐hydroxy‐containing para ‐quinone methides. The reaction relies on an unprecedented formal [4+1]‐annulation of these quinone methides with allenoates in the presence of a commercially available chiral phosphine catalyst. The chiral dihydrobenzofurans were obtained as single diastereomers in yields up to 90 % and with enantiomeric ratios up to 95:5.

Construction of Oxygen‐ and Nitrogen‐based Heterocycles from p‐Quinone Methides

“…Wang and co-workers accomplished a chiral bifunctional phosphonium salt (25) catalyzed highly enantio-and diastereo-selective [4 + 1]-annulation of 2-hydroxyphenyl-substituted p-QMs (16) with α-halogenated ketones (23) to obtain enantiomerically pure 2,3-dihydrobenzofuran derivatives (24) [Scheme 5]. [22] The control experiments suggested that, the p-QM ( 16) initially undergoes a base-mediated nucleophilic substitution reaction with 23 to produce 26, which, under the influence of the chiral catalyst 25, undergoes an enantioselective intramolecular 1,6-conjugate reaction to generate the desired product 24 with excellent enantioselectivities.…”

“…A fascinating organocatalytic protocol, based on phosphine catalysis, has been reported by Waser and co-workers to access enantiomerically-enriched dihydrobenzofurans (31) from 16 and allenoate (30) [Scheme 7]. [24] Waser's approach basically involves the activation of 30 by a chiral phosphine catalyst followed by a highly enantioselective 1,6-conjugate addition reaction of 32 with 16 to generate the zwitterionic intermediate 33. This intermediate 33, afterwards experiences a series of proton transfers and, then finally, undergoes an intramolecular cyclization to form the product 31 along with the phosphine catalyst.…”

Recent Advances in Phosphine‐Promoted (4 + 1) Annulation Reactions

“…Very recently, an asymmetric (4 + 1) annulation of ortho ‐hydroxy‐ para ‐quinone methides 42 with α‐substituted allenoates was further developed by the same group. By employing a commercially available chiral spiro phosphine catalyst 44 and in the presence of two equivalents K 2 CO 3 , the (4 + 1) annulation reaction smoothly afforded the corresponding dihydrobenzofurans 43 in moderate to high yields with exclusive diastereoselectivity and high enantiomeric ratio (Scheme ) …”

Recent Advances in Synthetic Strategies to 2,3-Dihydrobenzofurans

“…48 In 2019, Waser and co-workers started from o-hydroxyphenyl-substituted p-quinone methides in an asymmetric catalytic synthesis of highly functionalized DHBs. 49 The reaction relied on a formal [4+1]-annulation of these quinone methides with allenoates in the presence of a commercially available chiral phosphine catalyst. Chiral DHBs were obtained as single diastereomers up to 84% yield and with up to 95:5 er…”