Enantioselective Acyl Migration Reactions of Furanyl Carbonates with Chiral DMAP Derivatives

Abstract

An efficient enantioselective acyl migration reaction of furanyl carbonates was developed to construct all‐carbon quaternary stereogenic centers. In some cases, the reactions required only 0.05 mol % (minimum 500 ppm) of catalyst and showed a high turnover frequency value (TOF; 3640 h−1). Multigram‐scale reactions (10 grams) also proceeded with high enantioselectivity (>99:1 e.r.) in quantitative yield. The catalyst was robust and easily recovered in 98 % yield. A wide range of functional groups were tolerated (15 examples, >98 % yield, up to >99:1 e.r.), and a variety of optically active 3,3′‐disubstituted benzofuranone derivatives, which are useful intermediates for the synthesis of natural products and pharmaceuticals, were efficiently obtained. Control experiments on the catalyst structure (e.g., catalyst 1 a vs. 1 a′ and 1 a′′) and computational calculations revealed that both the catalytic activity and enantioselectivity should be enhanced by hydrogen bonding between catalyst and substrate. Moreover, this system was applied to the challenging γ‐selective acyl migration reaction of furanyl carbonates with high γ‐selectivity and high enantioselectivity (α:γ=10:90, 95:5 e.r.).

Biocatalytic Construction of Quaternary Centers by Aldol Addition of 3,3-Disubstituted 2-Oxoacid Derivatives to Aldehydes

“…Therefore, synthetic access to this type of compound can be regarded as significant and a challenging task for organic chemists. Indeed, creation of quaternary stereocenters is elusive mainly due to the steric hindrance between the carbon substituents, and consequently, considerable efforts have been dedicated to implement chemical methodologies for this purpose. ,, These encompass long-established approaches such as Claisen rearrangement and Diels–Alder reaction up to the most recent ones based on transition metal catalysis ,,, and organocatalytic reactions. , However, innovative procedures expanding the range of structurally diverse products with improved efficacy, simplicity, and stereoselectivity are key for advancing the field of chemical synthesis. , …”

Recent advances in catalytic asymmetric [1,3]-rearrangement reactions

“…Later in 2019, they further expanded the scope of this work by changing substituents on chiral nucleophilic catalysts and skeletons of substrates (Scheme 10, top). 31 They explored the acyl migration reaction of furanyl carbonates 14 with low catalyst loading (1 mol% or less) and all the test substrates presented high reactivity. The desired products 15 were obtained in moderate to excellent yields (>98%) with good to excellent asymmetric induction (up to >99 : 1 er).…”

Preparation of chiral DMAP derivatives and investigation on their enantioselective catalytic activity in benzazetidine synthesis and kinetic resolutions of alcohols

“…In these compounds the chirality arises from the restricted rotation along the aryl-aryl single bond [28][29][30] in position 3 on the pyridine ring. In recent examples, Suga et al, following a similar approach, proposed the use of an axially chiral compound based on the BINOL skeleton [31,32] provided with bulky groups [33,34]. These catalysts provided good enantioselectivity although their synthesis is elaborated and expensive.…”