Synthesis of Enantiomerically Pure Secondary γ-Halo Allylic Alcohols and Their Use in the Synthesis of Leukotrienes

In the first part of this account, a practical and general method for the synthesis of enantiomerically pure secondary γ-halo allylic alcohols is described. This involves the Sharpless kinetic resolution of secondary γ-trimethylsilyl, γ-tributylstannyl, and γ-halo allylic alcohols, which proceeds with very large rate differences for the two enantiomers, and the facile conversions of the resulting optically active allylic alcohols and/or epoxy alcohols to the γ-halo allylic alcohols. The Sharpless asymmetric epoxidation of primary allyl alcohols possessing a heteroatom substituent at the olefinic position and synthetic applications of the resulting epoxy alcohols are also described. In the second part of the review, highly stereoselective synthetic methods for preparation of biologically active lipoxygenase metabolites of arachidonic acid are discussed which include leukotriene B₄, hydroxyeicosatetraenoic acids, and lipoxins. This synthetic method involves the palladium-catalyzed coupling reaction of chiral γ-halo allylic alcohols with organoboranes or acetylenes as the key step. The synthesis of LTB₄ analogues and their biological activities are also briefly discussed. 1. Introduction 2. Kinetic Resolution of γ-Heteroatom Substituted Allylic Alcohols 2.1 Kinetic Resolution of γ-Trimethylsilyl Allylic Alcohols 2.2 Preparation of (E)- and (Z)-γ-Halo Allylic Alcohols 2.3 Kinetic Resolution of γ-Tributylstannyl Allylic Alcohols and γ-Iodo Allylic Alcohols 2.4 Asymmetric Epoxidation of 3-Heteroatom Substituted Allyl Alcohols 3. Synthesis of Leukotrienes 3.1 Synthesis of Leukotriene B₄, 20-Hydroxyleukotriene B₄, and Leukotriene B₃ 3.2 Synthesis of LTB Analogues and Their Biological Activities 3.3 Synthesis of Metabolites of the Lipoxygenase Cascade