A chiral fluoride-catalyzed asymmetric cascade sulfa-Michael/aldol condensation reaction of 1,4-dithiane-2,5-diol and a series of α,β-unsaturated ketones is described to access chiral trisubstituted tetrahydrothiophene derivatives. The target products, including the spiro tetrahydrothiophene derivatives bearing a five-, six-, and seven-membered ring, were highly functionalized and showed high ee value. This established protocol realized a highly enantioselective reaction with a catalytic amount of KF and Song's chiral oligoEG via in situ generated chiral fluoride to construct useful heterocyclic skeletons with great complexity.

Described herein is the enantioselective construction of oxygen-containing [5-6-5] tricyclic heterocycles by an organocatalyzed asymmetric [4+2] cycloaddition of vinylidene ortho-quinone methides and benzofurans. According to this methodology, a series of oxygen-containing [5-6-5] tricyclic heterocycles with various functional groups were synthesized in excellent enantio- and diastereoselectivities (>99 % ee, >20:1 d.r.). Furthermore, the deuterium-labeling experiments and high-resolution mass spectroscopy demonstrated that a vinylidene ortho-quinone methide intermediate was involved and possibly resulted from a prototropic rearrangement of 2-ethynylphenol. Remarkably, a catalyst loading as low as 0.1 mol %, and a gram-scale synthesis were achieved for this transformation.

Heterocyclic skeletons play major roles in pharmaceuticals and biological processes. Cycloaddition reactions are most suitable synthetic tools to efficiently construct chemically diverse sets of heterocycles with great structural complexity owing to the simultaneous or sequential formation of two or more bonds, often with a high degree of selectivity. Herein, we report an unprecedented formal cycloaddition of N-Boc-N-hydroxy amido sulfones as the nitrone precursors with terminal-hydroxy α,β-unsaturated carbonyls in the presence of Song's chiral oligoethylene glycol as a cation-binding catalyst and KF as a base to afford a wide range of highly enantio- and diastereo-enriched six-membered dioxazinane and seven-membered dioxazepane heterocycles. In this process, nitrones as well as terminal-hydroxy α,β-unsaturated carbonyls serve as "amphiphilic" building units, and the reaction proceeds through a tandem pathway sequence of oxa-Mannich reaction/oxa-Michael reaction/tautomerization/protonation. The cation-binding catalysis in a densely confined chiral space in situ formed by the incorporation of potassium salt is the key to this successful catalysis. This strategy opens a new pathway for the asymmetric synthesis of diverse heterocyclic skeletons of great complexity.

The development and characterization of enantioselective catalytic kinetic resolution of allylic alcohols through asymmetric isomerization with chiral BINOL derivatives-based alkoxides as bifunctional Brønsted base catalysts were described in the study. A number of chiral BINOL derivatives-based alkoxides were synthesized, and their structure−enantioselectivity correlation study in asymmetric isomerization identified a promising chiral Brønsted base catalyst, which afforded various chiral secondary allylic alcohols (ee up to 99%, S factor up to >200). In the mechanistic study, alkoxide species were identified as active species and the phenol group of BINOL largely affected the high reactivity and enantioselectivity via hydrogen bonding between the chiral Brønsted base catalyst and substrates. The strategy is the first successful synthesis strategy of various chiral secondary allylic alcohols through enantioselective transitionmetal-free base-catalyzed isomerization. The applicability of the strategy had been demonstrated by the synthesis of the bioactive natural product (+)-veraguensin.

Described herein is the enantioselective construction of oxygen‐containing [5‐6‐5] tricyclic heterocycles by an organocatalyzed asymmetric [4+2] cycloaddition of vinylidene ortho‐quinone methides and benzofurans. According to this methodology, a series of oxygen‐containing [5‐6‐5] tricyclic heterocycles with various functional groups were synthesized in excellent enantio‐ and diastereoselectivities (>99 % ee, >20:1 d.r.). Furthermore, the deuterium‐labeling experiments and high‐resolution mass spectroscopy demonstrated that a vinylidene ortho‐quinone methide intermediate was involved and possibly resulted from a prototropic rearrangement of 2‐ethynylphenol. Remarkably, a catalyst loading as low as 0.1 mol %, and a gram‐scale synthesis were achieved for this transformation.