Catalytic Enantioselective Synthesis of Axially Chiral Diarylmethylidene Indanones

Abstract

We describe the first atropselective Suzuki−Miyaura cross-coupling of β-keto enol triflates to access axially chiral (Z)diarylmethylidene indanones (DAIs). The chemical, physical, and biological properties of DAIs are unknown, despite their being structurally similar to arylidene indanones, primarily due to the lack of racemic or chiral methods. Through this work, we demonstrate a general and efficient protocol for the racemic as well as the atropselective synthesis of (Z)-DAIs. An unusual intramolecular Morita−Baylis−Hillman reaction is utilized for the Z-selective synthesis of β-keto enol triflates. ■ ASSOCIATED CONTENT * sı Supporting InformationThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.1c01671.Experimental details and characterization data for all new compounds ( 1 H NMR, 13 C NMR) (PDF)Accession CodesCCDC 2057339 and 2057498 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk

Axially chiral alkenes: Atroposelective synthesis and applications

“…Diversely, Ramasastry recently reported the atroposelective Suzuki-Miyaura cross-coupling reaction of β-keto enol triflates (122) with 1naphthyl boronic acids (123) catalyzed by palladium in the presence of chiral bisoxazoline (BOX)-type ligand L6 (Scheme 21). Various axially chiral (Z)-diarylmethylidene indanones (124) were obtained with moderate to good enantioselectivities [67]. Comparing alkenes 124a-124c, ortho-substituent other than alkoxy groups on boronic acids had little influence on product yield but could markedly diminish the enantioselectivity.…”

Asymmetric Construction of an Aryl‐Alkene Axis by Palladium‐Catalyzed Suzuki–Miyaura Coupling Reaction

“…Variously, the classic Suzuki–Miyaura coupling has found extraordinary utility in constructing aryl‐alkene scaffolds [12, 13] and even the challenging axially chiral biaryl skeletons [14] . With the exception of Gu's work that applied 2‐iodo‐3‐methylcyclohex‐2‐enones to construct 2‐arylcyclohex‐2‐enone atropisomers [4c] and Ramasastry's synthesis of axially chiral diarylmethylidene indanones, [7c] the formation of chiral aryl‐alkene axis from acyclic alkenes with this chemistry has remained challenging. This discrepancy stems from the marked structural difference of participating substrates where replacing one aryl partner with alkene could challenge selectivity control and reactivity in several aspects.…”

Asymmetric Construction of an Aryl‐Alkene Axis by Palladium‐Catalyzed Suzuki–Miyaura Coupling Reaction

“…Alkene‐aryl cross‐coupling removes one avenue for such control and judicious choice of alkene partners becomes crucial. This requirement of interaction handle was manifest in the asymmetric Suzuki‐Miyaura coupling developed by Ramasastry for enol triflates derived from arylidene indanones [7c] . Aside from weak coordination between ortho‐ ether group of aryl boronic acid and palladium center, enantiocontrol arises also from double π‐π stacking effect between the catalyst and aryl rings on enol triflate substrates.…”