Stereochemistry of Chiral 2-Substituted Chromanes: Twist of the Dihydropyran Ring and Specific Optical Rotation
Bei-Bei Yang,
Fan Gao,
Ya-Dong Yang,
Ru Wang,
Xin Li,
Li Li
Affiliations
Bei-Bei Yang
Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Fan Gao
Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Ya-Dong Yang
Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Ru Wang
Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Xin Li
Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Li Li
Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Chiral 2-substituted chromanes are important substructures in organic synthesis and appear in numerous natural products. Herein, the correlation between specific optical rotations (SORs) and the stereochemistry at C2 of chiral 2-substituted chromanes was investigated through data mining, quantum-chemical calculations using density functional theory (DFT), and mechanistic analyses. For 2-aliphatic (including acyloxy and alkenyl) chromanes, the P-helicity of the dihydropyran ring usually corresponds to a positive SOR; however, 2-aryl chromanes with P-helicity tend to exhibit negative SORs. 2-Carboxyl (including alkoxycarbonyl and carbonyl) chromanes often display small experimental SORs, and theoretical calculations for them are prone to error because of the fluctuating conformational distribution with computational parameters. Several typical compounds were discussed, including detailed descriptions of the asymmetric synthesis, absolute configuration (AC) assignment methods, and systematic conformational analysis. We hope this work will enrich the knowledge of the stereochemistry of chiral 2-substituted chromanes.
