Chiral sulfoxides synthesis

Colobert, F., Tito, A., Khiar, N., Denni, D., Medina, M. A., Martin-Lomas, M., Ruano, J.-L. G., Soiiadie, G. Enantioselective Approach to Polyhydroxylated Compounds Using Chiral Sulfoxides Synthesis of Enantiomerically Pure myo-lnositol and Pyrrolidine Derivatives. J. Org. Chem. 1998, 63, 8918-8921. 

The use of sulfoxides as chiral synthons has, over recent years, become a highly dependable protocol in synthetic organic chemistry. To some extent, however, the use of sulfoxides in asymmetric synthesis has been limited by the lack of a reliable and general method for their preparation in optically pure form. In this review we present the development of chiral sulfoxide synthesis via nucleophilic displacement at sulfur from the pioneering work of Andersen in 1962 to more recent methods. Sulfoxides have become associated with many diverse areas of synthetic chemistry indeed, their ability to act as a handle for the stereoselective generation of chirality at proximate centres has attracted much research worldwide. 

For a review of the synthetic uses of 3-keto sulfoxides, sulfones, and sulfides, see Trost, B.M. Chem. Rev., 1978, 78, 363. For a review of asymmetric synthesis with chiral sulfoxides, see Solladie, G. Synthesis, 1981, 185. 

Marino, J.P., Bogdan, S., Kimura, K. (1992) The Enantioselective Synthesis of (—)-Physostigmine via Chiral Sulfoxides. Journal of the American Chemical Society, 114, 5566-5572. 

Except for the syntheses using terpene-derived starting materials (Schemes 13.7, 13.8, and 13.9), the previous juvabione syntheses all gave racemic products. Some of the more recent juvabione syntheses are enantiospecific. The synthesis in Scheme 13.16 relied on a chiral sulfoxide that undergoes stereoselective addition to cyclohexenone to establish the correct relative and absolute configuration at C(4) and C(7). The origin of the stereoselectivity is a chelated TS that leads to the observed product.20... 

Scheme 18.5 Synthesis of the insect pheromone 12 from chiral sulfoxide 13 (pTol = p-tolyl) [23].

Two formal syntheses of (-)- [80] and (+)-kumausallene [81] followed this route and relied on the enantioselective preparation of the 2,6-dioxabicyclo[3.3.0]octane core 69 starting from diethyl tartrate or an appropriate chiral sulfoxide. In contrast, Evans et al. [82] used a distinct biomimetic approach in their enantioselective synthesis of the natural product (-)-62 (Scheme 18.23). 

Chiral sulfoxides play a key role in sulfur stereochemistry. Therefor much effort has been devoted to elaboration of convenient methods for their synthesis. Until now, chiral sulfoxides have been obtained in the following ways ... 

The most important and widely used approach to chiral sulfoxides is the method developed by Andersen (5) based on the reaction between the diastereomerically pure (or strongly enriched in one dia-stereomer) menthyl arenesulfinates and Grignard reagents. The first stereospecific synthesis of optically active (+H7 )-ethyl p-tolyl sulfoxide 22 was accomplished in 1962 by Andersen (75) from (-)-(iS)-menthyl p-toluenesulfmate 45 and ethylmagnesium iodide. 

The Andersen synthesis of chiral sulfoxides has also been extended to diastereomerically or enantiomerically pure arenesulfinamides, which on treatment with methyllithium give optically active methyl aryl sulfoxides (83,85). The use of menthyl sulfinates in the synthesis of sulfoxides has been exploited in the preparation of optically active sulfoxides 47 and 48, which are chiral by virtue of isotopic substitution, H- D (86), and (87), respectively. More recent... 

An alternative stereospecific synthesis of chiral sulfimides reported by Nudelman (137) consists of the reaction of the diastereomeric menthyl p-toluenesulfinimidoates 90 with Gri ard reagents giving the optically active sulfimide 91. This reaction, like the Andersen synthesis of chiral sulfoxides, proceeds with inversion of configura-... 

Wudl and Lee (96,97) reported the first preparation and resolution of the cyclic diastereomeric amidosulfites 58, which have been successfully used in the synthesis of chiral sulfoxides. A mixture of diastereomeric menthyl dimethylamidosulfites (100) was obtained in the reaction of racemic dimethylaminosulfinyl chloride (101) with menthol in the presence of pyridine (149). The degree of asymmetric... 

The synthesis of A -unsubstituted sulfoximides in the reaction of chiral sulfoxides with <9-mesitylsulfonylhydroxylamine follows the same steric course (180). Similarly, the reaction of (+)-(i )-methyl-p-... 

It is not the purpose of this section to discuss the synthesis of optically active sulfoxides which have recently been reviewed9. However, it is important to add recent results describing more efficient ways to introduce a chiral sulfoxide group in a molecule. 

Chiral sulfoxides are useful intermediates in asymmetric synthesis. A number of methods can be used for their preparation. For example, enantiomerically pure p-tolylsulfoxides can be obtained by displacing a dimethylphosphonylmethyl moiety, a carbon leaving... 

Chiral sulfoxides have emerged as versatile building blocks and chiral auxiliaries in the asymmetric synthesis of pharmaceutical products. The asymmetric oxidation of prochiral sulfides with chiral metal complexes has become one of the most effective routes to obtain these chiral sulfoxides.We have recently developed a new heterogeneous catalytic system (WO3-30% H2O2) which efficiently catalyzes both the asymmetric oxidation of a variety of thioethers (1) and the kinetic resolution of racemic sulfoxides (3), when used in the presence of cinchona alkaloids such as hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether [(DHQD)2-PYR], Optically active sulfoxides (2) are produced in high yields and with good enantioselectivities (Figure 9.3). ... 

Review,5 Solladie has reviewed use of nucleophiles containing a chiral sulfoxide group in asymmetric synthesis (140 references). 

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