Nucleophiles asymmetric epoxidations

Dual activation of nucleophile and epoxide has emerged as an important mechanistic principle in asymmetric catalysis [110], and it appears to be particularly important in epoxide ARO reactions. Future work in this area is likely to build on the concept of dual substrate activation in interesting and exciting new ways. 

Alternatively, epoxides can be formed with concomitant formation of a C-C bond. Reactions between aldehydes and various carbon nucleophiles are an efficient route to epoxides, although the cis. trans selectivity can be problematic (see Section 9.1.4). Kinetic resolution (see Section 9.1.5.2) or dihydroxylation with sequential ring-closure to epoxides (see Section 9.1.1.3) can be employed when asymmetric epoxidation methods are unsatisfactory. 

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

Asymmetric epoxidation of a prochiral alkene is an appealing process because two stereogenic centers are established in the course of the reaction. Often, the starting alkene is inexpensive. There have been several interesting recent advances in the asymmetric nucleophilic epoxidation. 

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. 

Nucleophilic ring opening of epoxy sugars is a valuable method for the synthesis of many modified sugar derivatives. The reaction is accompanied by Walden inversion, and a wide range of nucleophiles can be used. The cyclic nature of epoxides renders the competing elimination process stereoelectronically unfavourable. For asymmetric epoxides, in principle, two regio-isomeric products can be formed however, in... 

The first enantioselective total synthesis of l -(—)-cembrene A (59) and / -( )-nephthenol (40) were achieved by employing an intramolecular nucleophilic addition of sulfur-stabilized carbanion to asymmetric epoxide as the key step, starting from L-serine (Scheme 6-13). ... 

A polymeric binaphthyl zinc complex has been used for related epoxidation reactions <1999JOC8149>.A bimetallic samarium-based Lewis acid complex catalyzes the nucleophilic epoxidation of unsaturated carbonyl compounds very efficiently <2002JA14544>. The use of amino acids has organocatalysts for asymmetric epoxidations of enones and enals has been investigated <2005OL2579, 2005JA6964>. 

Nucleophilic reduction by telluride ion of oxirane tosylates provides allylic alcohols, presumably via telluriranes as shown in Equation (12) and Table 7 <1997T12131>. When used in conjunction with the Sharpless-Katsuki asymmetric epoxidation, optically active transposed allylic alcohols can be made in high enantiomeric excess <1993JOC718, 1994JOC4311, 1994JOG4760>. 

Alcohols can be obtained from many other classes of compounds such as alkyl halides, amines, al-kenes, epoxides and carbonyl compounds. The addition of nucleophiles to carbonyl compounds is a versatile and convenient methc for the the preparation of alcohols. Regioselective oxirane ring opening of epoxides by nucleophiles is another important route for the synthesis of alcohols. However, stereospe-cific oxirane ring formation is prerequisite to the use of epoxides in organic synthesis. The chemistry of epoxides has been extensively studied in this decade and the development of the diastereoselective oxidations of alkenic alcohols makes epoxy alcohols with definite configurations readily available. Recently developed asymmetric epoxidation of prochiral allylic alcohols allows the enantioselective synthesis of 2,3-epoxy alcohols. 

Reactions of chiral allylic boranes with carbonyl compounds Reactions of chiral allyl boranes with imines Asymmetric Addition of Carbon Nucleophiles to Ketones Addition of alkyl lithiums to ketones Asymmetric epoxidation with chiral sulfur ylids Asymmetric Nucleophilic Attack by Chiral Alcohols Deracemisation of arylpropionic acids Deracemisation of a-halo acids Asymmetric Conjugate Addition of Nitrogen Nucleophiles An asymmetric synthesis of thienamycin Asymmetric Protonation... 

Sharpless asymmetric epoxidation (chapter 27) of the allylic alcohol 148 with cumyl hydroperoxide and (+)-di-isopropyl tartrate (DIPT) gave the epoxide 149 in excellent yield and enantiomeric purity. The other enantiomer could be made simply by using the other enantiomer of DIPT. The problem is now how to react the epoxide regiospecifically with a nitrogen nucleophile ... 

---