Enantioselective Synthesis of anti–syn-Trihalides and anti–syn–anti-Tetrahalides via Asymmetric β-Elimination

Journal of the American Chemical Society

4 years ago

Enantioselective Synthesis of anti–syn-Trihalides and anti–syn–anti-Tetrahalides via Asymmetric β-Elimination

Dongmei Li, Nan Zhang, Choong Eui Song, Hailong Yan, Yidong Liu, Shilong Luo, Yu Tan, Wenling Qin, Shiqi Jia

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 anti–syn-trihalides and anti–syn–anti-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 E2 mechanism. This strategy opens a new pathway for the asymmetric synthesis of contiguous halide-bearing stereocenters of great complexity.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b02076

DOI: 10.1021/jacs.7b02076