Synthetic Applications of Chiral Unsaturated Epoxy Alcohols Prepared by Sharpless Asymmetric Epoxidation

Abstract

An overview of the synthesis and applications of chiral 2,3-epoxy alcohols containing unsaturated chains is presented. One of the fundamental synthetic routes to these compounds is Sharpless asymmetric epoxidation, which is reliable, highly chemoselective and enables easy prediction of the product enantioselectivity. Thus, unsaturated epoxy alcohols are readily obtained by selective oxidation of the allylic double bond in the presence of other carbon-carbon double or triple bonds. The wide availability of epoxy alcohols with unsaturated chains, the versatility of the epoxy alcohol functionality (e.g. regio- and stereo-selective ring opening; oxidation; and reduction), and the arsenal of established alkene chemistries, make unsaturated epoxy alcohols powerful starting materials for the synthesis of complex targets such as biologically active molecules. The popularization of ring-closing metathesis has further increased their value, making them excellent precursors to cyclic compounds.

Enantioselective One‐Pot Catalytic Synthesis of 4,5‐Epoxy‐3‐alkanols and 1‐Phenyl‐2,3‐epoxy‐1‐alkanols from α,β‐Unsaturated Aldehydes

“…It was observed that all substrates afforded the allylic alcohols in very good yields and good or perfect enantioselectivity (entries 1-13). Higher diastereoselectivities were achieved for enals that lead to A 1,3 strain instead of A 1,2 strain (see entries 6-8 vs. entries [1][2][3][4][5], and an inversion in the diastereoselection of the process was observed. Catalytic asymmetric ethyl transfer to α,β-unsaturated aldehydes in the presence of 1.…”

“…In 1965 a low level of stereoinduction was already obtained by Henbest, using (+)-peroxycamphoric acid. [2,4] The original Sharpless-Katsuki asymmetric epoxidation requires the use of catalytic amounts of titanium isopropoxide and tartrate ester ligands, tert-butyl hydroperoxide, and molecular sieves. This well-known achievement allowed high stereocontrol to be obtained in the epoxidation of allylic alcohols, including the kinetic resolution (KR) of secondary alcohols.…”

Biocatalysis as an alternative for the production of chiral epoxides: A comparative review

“…The predominant approach for the asymmetric epoxidation of allylic alcohols is through the titanium-catalyzed Sharpless epoxidation, which can usually achieve the enantioselective epoxidation of primary allylic alcohols catalyzed by l-(+)/d-(−)-diisopropyl tartrate and titanium tetraisopropoxide (Ti(O-i-Pr) 4 ) using tert-butyl hydroperoxide (TBHP) as the oxidant [10,22,69,70]. The absolute configuration of the resulting epoxide can be easily predicted using a rule developed by Sharpless, which correlates to the enantiomer of the tartrate used.…”

“…Several reviews on the preparation of chiral epoxides have been published [3,7,8,[22][23][24][25][26]. This review does not seek to provide a comprehensive list of all kinds of synthetic/enzymatic methods, but rather to emphasize the potential of biocatalysis in the preparation of chiral epoxides.…”

Concise, Protecting-Group-Free Synthesis of (+)-Nemonapride <i>via</i> Eu(OTf)₃-Catalyzed Aminolysis of 3,4-Epoxy Alcohol

“…1,2) Along with expanding the scope of catalytic enantioselective epoxidation reactions, the structural diversity of chiral epoxides is increased, [3][4][5][6][7][8] inspiring chemists to develop methods that conduct a selective nucleophilic ring opening of the epoxide. [9][10][11][12][13] To date, a number of reagents and conditions that lead to the regio-and stereocontrolled installation of various nucleophiles have been developed employing Lewis acid catalysis. 14) Among potential nucleophiles, N-nucleophiles, 15) such as amines, azides, amides, carbamates, and so on, have received considerable attention because the reaction allows access to β-amino alcohols, 16,17) which are versatile intermediates for biologically active compounds, chiral ligands, and catalysts.…”