Epoxide synthesis addition reactions

In spite of their intrinsic synthetic potential, addition reactions of metal enolates of non-stabilized esters, amides, and ketones to epoxides are not widely used in the synthesis of complex molecules. Following the seminal work of Danishefsky [64], who introduced the use of Et2AlCl as an efficient catalyst for the reaction, Taylor obtained valuable spiro lactones through the addition reaction of the lithium eno-late of tert-butyl acetate to spiro-epoxides, upon treatment of the corresponding y-... 

An alternative to the synthesis of epoxides is the reaction of sulfur ylide with aldehydes and ketones.107 This is a carbon-carbon bond formation reaction and may offer a method complementary to the oxidative processes described thus far. The formation of sulfur ylide involves a chiral sulfide and a carbene or carbenoid, and the general reaction procedure for epoxidation of aldehydes may involve the application of a sulfide, an aldehyde, or a carbene precursor as well as a copper salt. This reaction may also be considered as a thiol acetal-mediated carbene addition to carbonyl groups in the aldehyde. 

The successful synthesis of 2-thienyl and substituted 2- and 3-thienyl-acetylenes in yields as high as 60-80% opened a wide variety of synthetic applications. Various addition reactions with carbonyl compounds or epoxides could be carried out with ease. Aliphatic as well as aromatic amine addition reactions, or condensation reactions with hydrazine or hydroxylamine could be easily performed. 

Herein we will focus on the recent development of vinylogous [1] aldol reactions and their application in the synthesis of natural products [2-5]. In particular the synthesis of unsaturated esters through the vinylogous Mukaiyama aldol reaction is of great interest, since it provides rapid access to larger carbon frameworks and allows for a wide variety of transformations of the double bond (dihydroxylation, epoxidation, cuprate addition etc.). 

Review M. G. Finn and K. B. Sharpless, On the Mechanism of Asymmetric Epoxidation with Titanium-Tartrate Catalysts, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 5, Chap. 8, Academic Press, New York, 1985 R. A. Johnson and K. B. Sharpless, Addition Reactions with Formation of Car-... 

Halohydrins are useful intermediates especially in the synthesis of epoxides. The main reaction is usually accompanied by the formation of a dihalide. When the reactions are performed in the presence of acetic acid, then acetates of the hydrins can be the predominant products. With several exceptions, alkenes with a nonfluorinated C = C bond have been subjected to halohydrinations. Halogen cations usually undergo addition to the substituted carbon of the C = C bond in (fluoroalkyl)ethenes. 

The first issue confronted by Myers was preparation of homochiral epoxide 7, the key intermediate needed for his intended nucleophilic addition reaction to enone 6. Its synthesis began with the addition of lithium trimethylsilylacetylide to (R)-glyceraldehyde acetonide (Scheme 8.6).8 This afforded a mixture of propargylic alcohols that underwent oxidation to alkynone 10 with pyridinium dichromate (PDC). A Wittig reaction next ensued to complete installation of the enediyne unit within 11. A 3 1 level of selectivity was observed in favour of the desired olefin isomer. After selective desilylation of the more labile trimethylsilyl group from the product mixture, deacetalation with IN HC1 in tetrahydrofuran (THF) enabled both alkene components to be separated, and compound 12 isolated pure. 

A. S. Rao, Addition Reactions with Formation of Carbon-Oxygen Bonds (i) General Methods of Epoxidation, in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 7, 357, Pergamon Press, Oxford, 1991. 

The isomorphous substitution of T atoms by other elements produces novel hybrid atom molecular sieves with interesting properties. In the early 1980s, the synthesis of a zeolite material where titanium was included in the MFI framework of silicalite, that is, in the aluminum-free form of ZSM-5, was reported. The name given to the obtained material was titanium silicalite (TS-1) [27], This material was synthesized in a tetrapropylammonium hydroxide (TPAOH) system substantially free of metal cations. A material containing low levels (up to about 2.5 atom %) of titanium substituted into the tetrahedral positions of the MFI framework of silicalite was obtained [28], TS-1 has been shown to be a very good oxidation catalyst, mainly in combination with a peroxide, and is currently in commercial use. It is used in epoxidations and related reactions. TS-1, additionally an active and selective catalyst, is the first genuine Ti-containing microporous crystalline material. 

The selected examples by Cole et al. [120] and Shimizu et al. [121] reported the parallel synthesis of a small library of solid supported dipeptide Schiff bases as ligands for the Ti-catalyzed enantioselective addition of trimethylsilyl cyanide to meso epoxides, and the determination of their catalytic activity on different substrates. The catalyzed addition reaction and the general structure of the dipeptide ligands are shown in Figure 7.15. 

The intermediate resulting from addition of H is similar to the intermediate in a Williamson ether synthesis. Intramolecular reaction occurs to form the epoxide. 

In the literature, two additional reactions following addition esterification have been treated using the cascade theory the addition esterification followed by polyetherification with epoxide groups in excess (a reaction used for crosslinking of carboxyl terminated polydienes) and addition esterification followed by transesterification. Transesterification often interferes wherever hydroxyester groups are formed, for example, in synthesis of linear oligomeric polyesters from diepoxide and acids. As has been explained before, polyetherification is an initiated reaction and, therefore, the statistical treatment offerend in Refs. should be revised. Below we show the treatment of transesterification for a system composed of a diepoxide and a dicar boxylic acid. 

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