title: A scalable, nonenzymatic synthesis of highly stereopure difunctional C4 secondary methyl linchpin synthons.
abstract: In response to the continuing widespread use of heterodifunctional C4 secondary methyl building blocks in asymmetric synthesis, we have developed a mole-scale, two-step synthesis of a 1:1 mixture of the diastereomers of 3-bromo-2-methyl-1-propyl camphorsulfonate (casylate). One isomer (2S) has been crystallized to >99:1 dr in ∼25% yield. Equilibration of the mother liquor (enriched in 2R) to a 1:1 mixture and recrystallization significantly raises the overall yield of 2S. Applications of 2S include chemoselective Grignard coupling, enabling the very short synthesis of highly stereopure long-chain natural products containing remote, methyl-bearing stereogenic centers [e.g., (R)-tuberculostearic acid], with complete control of configuration. Also, Ag-mediated, completely chemoselective Br displacement from 2S leads to a range of >99:1 er difunctional synthons. Both applications incorporate concurrent recovery of CasO. The enantiomer of 2S can be made from commercial (1R)-10-CasOH.
authors.affiliation: Department of Chemistry, Syracuse University , Syracuse, New York 13244-4100, United States.
authors.forename: Shekar
authors.initials: S
authors.lastname: Mekala
authors.forename: Roger C
authors.initials: RC
authors.lastname: Hahn
mesh_terms: D002164:Camphor / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013229:Stearic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C000600209:3-bromo-2-methyl-1-propyl camphorsulfonate; D013229:Stearic Acids; C026082:tuberculostearic acid; D002164:Camphor