Quinine-Promoted, Enantioselective Boron-Tethered Diels–Alder Reaction by Anomeric Control of Transition-State Conformation

Abstract

Diels-Alder reactions of tethered vinyl-metal species offer the opportunity to fashion highly functionalized diol intermediates for synthesis. We have developed the first enantioselective boron-tethered Diels-Alder reaction using quinine as a chiral promoter. Quinine recovery, enantioselectivity enhancement, and manipulation of the cyclohexene core are also investigated. DFT modeling calculations confirm the role of quinine as a bidentate ligand enhancing reaction rates. The enantioselectivity of the cycloaddition is proposed to originate from a boron-centered anomeric effect.

Boron and Silicon-Substituted 1,3-Dienes and Dienophiles and Their Use in Diels-Alder Reactions

“…Several reports of boron-substituted dienophiles for use in Diels-Alder reactions have appeared in the last few years as well. In 2018, Houck, Morgan, and co-workers reported a quinine-promoted, enantioselective, boron-tethered Diels-Alder reaction of a boron-substituted dienophile (82) (Scheme 23) [21]. In this work, a variety of dienols were tethered to phenylethenyl boronic acid and quinine was used as a chiral promoter to coordinate to boron for the subsequent intramolecular Diels-Alder reaction.…”

Organoboron Compounds Towards Asymmetric Pericyclic Reaction; Exploitation to Bioactive Molecule Synthesis

“…Next bicyclic zwitterion formation via [4+2] cycloaddition followed by intramolecular elimination resulted in a variety of dihydronaphthalenes with excellent ee . Recently Morgan group engaged various substitute alkenyl boronate ester as the effective dienophiles towards the intramolecular asymmetric DA reaction (Scheme 3c) [22] . Quinine being a bidentate ligand, gets chelated through five‐membered ring formation via transesterification.…”

“…Recently Morgan group engaged various substitute alkenyl boronate ester as the effective dienophiles towards the intramolecular asymmetric DA reaction (Scheme 3c). [22] Quinine being a bidentate ligand, gets chelated through five-membered ring formation via transesterification. A stereocontrolled BÀ N coordination based on anomeric effect imposed S-configuration, which is shown in T.S.-2.…”

Nickel- and Brønsted Acid-Catalyzed Redox-Neutral Coupling of 1,3-Dienes and Aldehydes for Synthesis of Dienols

“…Dienols are important structural motifs that not only widely exist in numerous bioactive compounds (Figure 1a), [1][2][3][4] but also act as versatile synthons in Diels-Alder reactions 5,6 and other reactions. 7,8 Although numerous methods have been developed to synthesize them, for example Wittig reaction and cross-coupling reactions, [9][10][11][12][13][14][15] carbonyl addition reactions that join diene precursors with carbonyl compounds would undoubtedly be more attractive pathways because of easier availability of carbonyls.…”