Enantioselective Synthesis of <i>anti</i>–<i>syn</i>-Trihalides and <i>anti</i>–<i>syn</i>–<i>anti</i>-Tetrahalides via Asymmetric β‑Elimination

Structural motifs containing contiguous halide-bearing stereocenters are common in natural products as well as bioactive molecules. A few successful examples have been reported in the area of asymmetric vicinal dihalogenation of alkenes for accessing dihalogenated products; in this report, an alternative generation method of contiguous halide-bearing stereocenters α,β,γ,δ relative to carbonyl group in excellent enantioselectivity is proposed by utilizing a Song’s oligoEG catalyst-catalyzed asymmetric β-elimination. According to this methodology, a wide range of <i>anti</i>–<i>syn</i>-trihalides and <i>anti</i>–<i>syn</i>–<i>anti</i>-tetrahalides with high levels of enantioselectivity were synthesized. The synthetic utility of the contiguous halide-bearing stereocenters was demonstrated by several transformations. The results of high-resolution mass spectrometry indicated that the favorable interaction between catalyst and one of the enantiomers of racemic contiguously multihalogenated ketone contributed to the original enantioselectivity of dehydrohalogenation. A deuterium kinetic isotope effect experiment revealed that this β-elimination reaction proceeds by the <i>E</i>2 mechanism. This strategy opens a new pathway for the asymmetric synthesis of contiguous halide-bearing stereocenters of great complexity

Asymmetric Synthesis of Trisubstituted Tetrahydrothiophenes via in Situ Generated Chiral Fluoride-Catalyzed Cascade Sulfa-Michael/Aldol Reaction of 1,4-Dithiane-2,5-diol and α,β-Unsaturated Ketones

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

Enantioselective Synthesis of <i>anti</i>–<i>syn</i>-Trihalides and <i>anti</i>–<i>syn</i>–<i>anti</i>-Tetrahalides via Asymmetric β‑Elimination

Structural motifs containing contiguous halide-bearing stereocenters are common in natural products as well as bioactive molecules. A few successful examples have been reported in the area of asymmetric vicinal dihalogenation of alkenes for accessing dihalogenated products; in this report, an alternative generation method of contiguous halide-bearing stereocenters α,β,γ,δ relative to carbonyl group in excellent enantioselectivity is proposed by utilizing a Song’s oligoEG catalyst-catalyzed asymmetric β-elimination. According to this methodology, a wide range of <i>anti</i>–<i>syn</i>-trihalides and <i>anti</i>–<i>syn</i>–<i>anti</i>-tetrahalides with high levels of enantioselectivity were synthesized. The synthetic utility of the contiguous halide-bearing stereocenters was demonstrated by several transformations. The results of high-resolution mass spectrometry indicated that the favorable interaction between catalyst and one of the enantiomers of racemic contiguously multihalogenated ketone contributed to the original enantioselectivity of dehydrohalogenation. A deuterium kinetic isotope effect experiment revealed that this β-elimination reaction proceeds by the <i>E</i>2 mechanism. This strategy opens a new pathway for the asymmetric synthesis of contiguous halide-bearing stereocenters of great complexity