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

Abstract

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.

Catalytic Asymmetric Generation of (Z)-Disubstituted Allylic Alcohols

“…[5][6][7]4 Other drawbacks to the KR include the need to separate the desired allylic alcohol from the epoxy alcohol product and a maximum yield of 50%. 20 More efficient methods to prepare allylic alcohols include asymmetric vinylation of aldehydes [21][22][23][24][25]13,15,[8][9][10][26][27][28] or ketones 29,30 (Scheme 2) and reductive coupling of alkynes and carbonyl compounds. 31-36 These methods simultaneously generate the C-C bond and a stereogenic center in a single step.…”

“…13,15,8,9,30,29,10,19,42 Synthons for these species are shown in Figure 1. The synthon for the (E)-disubstituted vinyl groups represented in Scheme 2 (A , Figure 1) is readily derived from hydrometallation of terminal alkynes.…”

Direct, Stereospecific Generation of (Z)-Disubstituted Allylic Alcohols

“…The catalytic asymmetric addition of vinylzinc reagents to aldehydes has recently engendered a great deal of attention. 1 The resulting allylic alcohols are versatile building blocks for the synthesis of enantioenriched allylic amines, 2 R-amino acids, 2 γ-unsaturated β-amino acids, 3 cyclopropyl alcohols, 4 epoxy alcohols, [5][6][7] and natural products. 8,9 The majority of asymmetric aldehyde vinylations have employed (E)-disubstituted vinylzinc reagents generated via hydroboration 10 or hydrozirconation 11 of terminal alkynes and transmetalation to zinc.…”

A new era for organic synthesis—highlights of the recent progress

“…A number of other reports have also appeared in the last two years, including the molybdenum carbonyl mediated tandem allenic Pauson-Khand reaction [76] in the presence of CO-the highly enantio-and diastereoselective one-pot synthesis [77] of acyclic epoxy alcohols and allylic epoxy alcohols, the domino ring-opening/rearrangement reaction [78] of 2,3-epoxy-1-alcohols and PIFA(phenyliodine(III) bis(trifluoroacetate)), the tandem [4+2]/1,3-dipolar [3+2] cycloaddition of oxadiazoles [79] that allowed direct access to the pentacyclic aspidosperma skeleton in a reaction cascade forming four new C-C bonds and three new rings, and a catalytic asymmetric three-component 1,4-addition/aldol reaction in the enantioselective synthesis [80] of the spirocyclic moiety of Vannusal A. All these will not be detailed here due to space limitation.…”