Epoxidations enoates

The epoxidation of alkenes is one of the most impoi4ant oxidation methods. Electrochemical epoxidation of electron-poor olefins such as enoates (154 155) and enones has been accomplished by using silver(III)oxo bis(2,2 -bipyridine) and similar complexes (Scheme 61) [241], )-Dimethyl glutaconate is electrolyzed in an MeCN-LiCl04/Ag0Ac)(bpy)-(Pt) system to give the trans-epoxide in 90% yield. 

This enzyme [EC 3.S.2.6] catalyzes the hydrolysis of (7E,9E,11Z,14Z) - (5vS,6.S) - 5,6 - epoxyicosa - 7,9,11,14 - tetra-enoate to form (6Z,8E,10E,14Z)-(55,12R)-5,12-dihy-droxyicosa-6,8,10,14-tetraenoate. This enzyme is highly specific yet it also converts 4,5-leukotriene A4 into leukotriene B4. Note also that epoxide hydrolase [EC 3.3.2.3] is not identical with this enzyme. 

The dianion derived from but-2-ynoic acid reacts with aldehydes to give 5-hydroxyalk-2-ynoates (539). Partial reduction over a Lindlar catalyst and acid-catalyzed cyclization of the resulting enoate gives the dihydropyran-2-one (78LA337). The route is exemplified by the synthesis of the naturally occurring massoia lactone (Scheme 200). In previous work (46JCS954) the hydroxyalkynoic acids themselves, obtained from epoxides and acetylene, were used. 

In contrast with metal-complex catalyzed transformations [52], enantioselective organocatalyzed intermolecular conjugate additions of O-nudeophiles seem to be limited to peroxides such as hydrogen peroxide or tert-butyl hydroperoxide. In these reactions the primary addition product, a / -peroxy enolate, reacts further to yield an epoxide (Scheme 4.31). Consequently, reactions of this type are covered in Section 10.2 Epoxidation of Enones and Enoates . 

As discussed in Section 10.1, asymmetric epoxidation of C=C double bonds usually requires electrophilic oxygen donors such as dioxiranes or oxaziridinium ions. The oxidants typically used for enone epoxidation are, on the other hand, nucleophilic in nature. A prominent example is the well-known Weitz-Scheffer epoxidation using alkaline hydrogen peroxide or hydroperoxides in the presence of base. Asymmetric epoxidation of enones and enoates has been achieved both with metal-containing catalysts and with metal-free systems [52-55]. In the (metal-based) approaches of Enders [56, 57], Jackson [58, 59], and Shibasaki [60, 61] enantiomeric excesses > 90% have been achieved for a variety of substrate classes. In this field, however, the same is also true for metal-free catalysts. Chiral dioxiranes will be discussed in Section 10.2.1, peptide catalysts in Section 10.2.2, and phase-transfer catalysts in Section 10.2.3. 

In the metal-free epoxidation of enones and enoates, practically useful yields and enantioselectivity have been achieved by using catalysts based on chiral electrophilic ketones, peptides, and chiral phase-transfer agents. (E)-configured acyclic enones are comparatively easy substrates that can be converted to enantiomeri-cally highly enriched epoxides by all three methods. Currently, chiral ketones/ dioxiranes constitute the only catalyst system that enables asymmetric and metal-free epoxidation of (E)-enoates. There seems to be no metal-free method for efficient asymmetric epoxidation of achiral (Z)-enones. Exocyclic (E)-enones have been epoxidized with excellent ee using either phase-transfer catalysis or polyamino acids. In contrast, generation of enantiopure epoxides from normal endocyclic... 

A chiral ytterbium complex formed from Yb(0-(-Pr)3 and 6,6 -diphenyl-BINOL catalyzed the asymmetric epoxidation of chalcone in 91% yield and 97% ee <2001TL6919>. A related reaction proceeds efficiently using enoates <2005JA8962>. 

A simple, divergent, asymmetric synthesis of the four stereoisomers of the 3-amino-2,3,6-trideoxy-L-hexose family was proposed by Dai and coworkers [222], which is based on the Katsuki-Sharpless asymmetric epoxidation of allylic alcohols (Scheme 13.115). Recently, A-trifluoroacetyl-L-daunosamine, A-trifluoroacetyl-L-acosamine, A-benzoyl-D-acosamine and A-benzoyl-D-nistosamine were derived from methyl sorbate via the methyl 4,5-epoxy-( -hex-2-enoates obtained via a chemoenzymatic method [223]. 

Apart from the significant clinical potential of 1 and its restricted natural supply, the attraction of laulimalide (1) as a synthetic target originates from its unique and complex molecular architecture. Specifically, its 16,17-epoxide is liable to nucleophilic attack from the 20-hydroxy group to form the more stable but biologically less active tetrahydrofuran isomer 2, and the 2,3-c/5-enoate moiety readily undergoes /Z-isomerization. To date, in addition to an impressive number of 15 approaches to key fragments, as many as ten total syntheses of 1 have been completed. 

Recently, reactions of acyclic vinyl epoxides have attracted increased attention. In many cases, regio-selectivity is strongly dependent upon substrate structure, with ( )- and (Z)-isomers providing different results. Similarly, stereoselectivity is the result of a complex interplay of steric and conformational effects, but anti addition to an s-trans conformation appears to be preferred. The regio- and stereo-selective ot-alkylation of "y,8-epoxy-a,p-enoates has been reported recently. Again, Sn2 selectivity was greater with cyanocuprates than with the harder homocuprates, but in no case was conjugate addition detected. 

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