Chiral peracids

Oxidation of sulfides by chiral peracids was investigated very early by Montanari et al. [36,37] and Balenovic etal. [38], but enantiomeric excesses were disappointingly low ( 10%). A detailed account of this area can be found in refs [15] and [39]. 

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The earliest attempts to obtain optically active sulfoxides by the oxidation of sulfides using oxidants such as chiral peracids did not fare well. The enantiomeric purities obtained were very low. Biological oxidants offered great improvement in a few cases, but not in others. Lately, some very encouraging progress has been made using chiral oxaziridines and peroxometal complexes as oxidants. Newer developments in the use of both chemical oxidants and biological oxidants are described below. 

In contrast to asymmetric oxidation of unsymmetrical sulfides with chiral peracids, microbial oxidation usually gives much better results. Thus, optically active phenyl benzyl sulfoxide was prepared by oxidation of the parent sulfide via fermentation with Aspergillus niger, NRRL 337, with 18% optical purity (42). Similarly, asymmetric... 

Since in principle the reactions of enantiomeric sulfoxides with a chiral reagent are expected to proceed at unequal rates, a possibility exists for obtaining chiral sulfoxides, especially when the reacting racemic sulfoxide is used in excess in relation to the chiral reagent. A typical example of such a kinetic resolution of a racemic sulfoxide is its reaction with a deficiency of chiral peracid, affording a mixture of optically active sulfoxide and achiral sulfone (62,63). However,... 

Although it was also Henbest who reported as early as 1965 the first asymmetric epoxidation by using a chiral peracid, without doubt, one of the methods of enantioselective synthesis most frequently used in the past few years has been the "asymmetric epoxidation" reported in 1980 by K.B. Sharpless [3] which meets almost all the requirements for being an "ideal" reaction. That is to say, complete stereofacial selectivities are achieved under catalytic conditions and working at the multigram scale. The method, which is summarised in Fig. 10.1, involves the titanium (IV)-catalysed epoxidation of allylic alcohols in the presence of tartaric esters as chiral ligands. The reagents for this asyimnetric epoxidation of primary allylic alcohols are L-(+)- or D-(-)-diethyl (DET) or diisopropyl (DIPT) tartrate,27 titanium tetraisopropoxide and water free solutions of fert-butyl hydroperoxide. The natural and unnatural diethyl tartrates, as well as titanium tetraisopropoxide are commercially available, and the required water-free solution of tert-bnty hydroperoxide is easily prepared from the commercially available isooctane solutions. 

This chiral peracid oxidation was used to convert the vinyl sulfide 3, derived from (S)-( + )-camphor-10-sulfonyl chloride, to a chiral sulfoxide (96 4 selectivity),... 

The use of chiral peracids was pioneered by Henbest1 who produced epoxides with an enantiomeric excess of 5% using ( + )-monoperoxycamphoric acid (1). The acid used was shown to be a mixture of isomers2 and later work improved enantiomeric excess in these reactions to 15% by using more highly purified epoxidizing agent. 

Peracetic acid was later replaced by m-chloroperbenzoic acid (MCPBA), which is easier to handle and relatively more stable than peracetic acid. Other solid per-acids including chiral peracids have been used in the synthesis of chiral oxaziridines (see Section IIl.l). Recently, MCPBA has been found to be effective in the preparation of oxaziridines with no substituent on the ring nitrogen, a class of oxaziridines that are rather unstable (Ref. 13 and references cited therein). Phase-transfer catalysis has been employed in an improved synthesis of Msulfonyloxa-ziridines. p-Nitroperbenzoic acid was used to oxidize an epoxy imine to an epoxyoxaziridine. ... 

The oxidation of chiral imines with peracids and the oxidation of achiral imines with chiral peracids to give optically active A-alkyl oxaziridines has been reviewed <84MI 112-01 >. The resolution of chiral A-alkyloxaziridine-3,3-dicarboxylic esters through the enzymatic hydrolysis of the racemic diesters, in moderate ees, has been reported <88CC1614>. 

Epoxidation. For asymmetric epoxidation of alkenes capable of H-bonding by aqueous H2O2 and AT,iV -diisopropylcarbodiimide the proline-based tripeptide 12 plays a catalytic role by transforming the aspartyl residue into a chiral peracid. ... 

Scheme 8.1. Generalized illustration of epoxidation of a fran -alkene using a chiral peracid R = a generic chiral substituent (in early work, monoperoxycamphoric acid was often used).

Thus, the aldol shown, which is susceptible to Sharpless-type epoxidation, has been obtained from phytal and the protected hydroquinone (ref. 120). Formation of the epoxide presumably with a chiral peracid (or perhaps with a conventional peracid relying on the asymmetry of the substrate) and then cleavage reductively in t-butyl methyl ketone containing lithium aluminium hydride led to a diol. The benzylic hydroxyl group of this was hydrogenolysed to afford the hydroquinone dimethyl ether in 85% yield. Ceric ammonium nitrate (CAN) oxidation afforded the intermediate benzoquinone hydrogenation of which was reported to result in 2R,4 R,8 R-a-tocopherol by, presumably, avoidance of a racemisation step. 

If the ester is applied both as solvent and as reactant, it is possible to use commercial 30-35% hydrogen peroxide without loss of reactivity. Additionally, perhydrolysis has a much broader substrate range, i.e., not only peroxy fatty acids but also branched and chiral peracids as well as peracetic and peracrylic acid can be prepared in situ. 

Non-racemic chiral peracids are of limited value for asymmetric epoxidation [9]. An asymmetric version of the related Payne procedure, mediated by a nitrile and hydrogen peroxide, has provided high ees [10]. 2-Cyanoheptahelicene 5 was reported to epoxidise frany-stilbene and a-methylstyrene under Payne conditions. 

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