Highly Enantio- and Diastereoselective One-Pot Synthesis of Acyclic Epoxy Alcohols and Allylic Epoxy Alcohols

• Published in: Journal of the American Chemical Society Vol. 127; no. 42; pp. 14668 - 14674
• Main Authors: Kelly, Ann Rowley, Lurain, Alice E, Walsh, Patrick J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 26.10.2005; Amer Chemical Soc
• Subjects: Alcohols - chemical synthesis; Alcohols - chemistry; Chemical reactivity; Chemistry; Chemistry, Multidisciplinary; Epoxy Compounds - chemical synthesis; Epoxy Compounds - chemistry; Exact sciences and technology; Molecular Structure; Organic chemistry; Physical Sciences; Reactivity and mechanisms; Science & Technology; Stereoisomerism; DIOXYGEN; REAGENTS; ALPHA,BETA-UNSATURATED KETONES; KINETIC RESOLUTION; COMPLEXES; ENONES; CATALYTIC ASYMMETRIC EPOXIDATION; HYDROGEN-PEROXIDE; ALDEHYDES; DISULFONAMIDE-TI(O-ISO-PR)4-DIALKYL ZINC SYSTEM; One pot reaction; Catalytic reaction; Enantioselectivity; Chemoselectivity; Catalyst selectivity; Transition metal Complexes; Complex catalyst; Experimental study; Tandem reaction; Allylic compound; Diastereoselectivity; Titanium Complexes; Addition reaction; Epoxidation; Secondary alcohol; Catalyst activity
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja051291k

In this report, we outline a highly enantio- and diastereoselective one-pot method for the efficient synthesis of synthetically useful acyclic epoxy alcohols and allylic epoxy alcohols. Our method takes advantage of a highly enantioselective C−C bond-forming reaction to set the initial chirality. The resulting allylic zinc alkoxide intermediate is then epoxidized in situ using either dioxygen or TBHP in the presence of a titanium tetraalkoxide. Epoxy alcohols with up to three contiguous stereocenters are formed in one pot with excellent enantio- and diastereoselectivity. In cases where the zinc alkoxide intermediates contain two different allylic olefins, the more electron-rich double bond is chemoselectively epoxidized to afford an allylic epoxy alcohol. This method represents a highly efficient, stereoselective, and chemoselective approach to the synthesis of a wide range of useful epoxy alcohol and allylic epoxy alcohol products that were previously difficult to access.