biostudies-literatureBartolo NDDivision of Materials ResearchNational Institute of General Medical SciencesNIGMS NIH HHS3042-3065https://www.ebi.ac.uk/biostudies/studies/S-EPMC9022492biostudies-literatureUnknown87(5)The addition of the highly reactive reagent allylmagnesium halide to α-substituted acyclic chiral ketones proceeded with high stereoselectivity. The stereoselectivity cannot be analyzed by conventional stereochemical models because these reactions do not conform to the requirements of those models. Instead, the stereoselectivity arises from the approach of the nucleophile to the most accessible diastereofaces of the lowest-energy conformations of the ketones. High stereoselectivity is expected, and the stereochemical outcome can be predicted, with conformationally biased ketones that have sterically distinguishable diastereofaces wherein only one face is accessible for nucleophilic addition. The conformations of the ketones can be determined by a combination of computational modeling and, in some cases, structure determination by X-ray crystallography.The Journal of organic chemistryConformationally Biased Ketones React Diastereoselectively with Allylmagnesium Halides.PMC9022492DMR-2002964R01 GM1292861R01GM129286Bartolo NDYang YWard MDDemkiw KMHu CTWoerpel KADillon AMRead JAValentin EMfalseConformationally Biased Ketones React Diastereoselectively with Allylmagnesium Halides.The addition of the highly reactive reagent allylmagnesium halide to α-substituted acyclic chiral ketones proceeded with high stereoselectivity. The stereoselectivity cannot be analyzed by conventional stereochemical models because these reactions do not conform to the requirements of those models. Instead, the stereoselectivity arises from the approach of the nucleophile to the most accessible diastereofaces of the lowest-energy conformations of the ketones. High stereoselectivity is expected, and the stereochemical outcome can be predicted, with conformationally biased ketones that have sterically distinguishable diastereofaces wherein only one face is accessible for nucleophilic addition. The conformations of the ketones can be determined by a combination of computational modeling and, in some cases, structure determination by X-ray crystallography.2022-01-01T00:00:00Z2022 Mar2024-10-18T20:36:40.234Z2024-10-18T20:36:40.234ZS-EPMC90224923516730010.1021/acs.joc.1c02844