Chirality of sulfoxides

Light DR, Waxman DJ, Walsh C. 1982. Studies on the chirality of sulfoxidation catalyzed by bacterial flavoenzyme cyclohexanone monooxygenase and hog liver flavin adenine dinucleotide containing monooxygenase. Biochemistry 21 2490-2498. 

How can the chirality of sulfoxides be made useful This area of research has received a lot of attention in the last 10-15 years, with many attempts to design reactions in which the chirality at sulfur is transferred to chirality at carbon. 0 - 0... 

D. R. Boyd, C. T. Walsh, and Y-C. J. Chen, S-oxygenases II—Chirality of sulfoxidation reactions. Sulfur Drugs and Related Organic Chemicals Chemistry, Biochemistry, and Toxiccdogy, Vol. 2 (L. A. Damani, ed.), Wiley, New York, 1989. 

The usefulness of chirality of sulfoxide as a sole chiral source was demonstrated. Use of chiral sulfoxides 25a,b afforded (S)-2 with 56% and 49% ee, respectively. 

In cyclic sulfoxides Che diastereomeric product ratio is even higher, and the chirality of the sulfur atom has been efficiently transferred to the carbon atom in synthesis. 

An achiral reagent cannot distinguish between these two faces. In a complex with a chiral reagent, however, the two (phantom ligand) electron pairs are in different (enantiotopic) environments. The two complexes are therefore diastereomeric and are formed and react at different rates. Two reaction systems that have been used successfully for enantioselective formation of sulfoxides are illustrated below. In the first example, the Ti(0-i-Pr)4-f-BuOOH-diethyl tartrate reagent is chiral by virtue of the presence of the chiral tartrate ester in the reactive complex. With simple aryl methyl sulfides, up to 90% enantiomeric purity of the product is obtained. 

Chiral acetylenic sulfoxides and related compounds in synthesis of heterocycles 97MI39. 

To control the stereochemistry of 1,3-dipolar cycloaddidon reacdons, chiral auxiliaries are introduced into either the dipole-part or dipolarophile A recent monograph covers this topic extensively ° therefore, only typical examples are presented here. Alkenes employed in asymmetric 1,3-cycloaddidon can be divided into three main groups (1) chiral allyhc alcohols, f2 chiral amines, and Hi chiral vinyl sulfoxides or vinylphosphine oxides. 

G. H. Posner, Addition of Organometallic Reagents to Chiral Vinyl Sulfoxides in Asymmetric Synthesis. J. D. Morrison, Ed. Vol. 2, p. 225, Academic, New York 1983. 

The stereogenic sulfur atom in sulfoxides is usually configurationally stable at room temperature thus, sulfoxides may be chiral based on this property alone1. In fact, there are many examples of optically active sulfoxides of both synthetic and natural origin. This chapter reviews the important methods for obtaining optically active sulfoxides, and discusses some reactions at sulfur which either leave the coordination number at three or increase it to four, generally with preservation of optical activity. It also describes briefly some recent studies on the conformational analysis and chiroptical properties of sulfoxides. 

Racemic mixtures of sulfoxides have often been separated completely or partially into the enantiomers. Various resolution techniques have been used, but the most important method has been via diastereomeric salt formation. Recently, resolution via complex formation between sulfoxides and homochiral compounds has been demonstrated and will likely prove of increasing importance as a method of separating enantiomers. Preparative liquid chromatography on chiral columns may also prove increasingly important it already is very useful on an analytical scale for the determination of enantiomeric purity. 

Arai Y., Koizumi T. Synthesis and Asymmetric Diels-Alder Reactions of Chiral. Alpha.,.Beta.-Unsaturated Sulfoxides Bearing a 2-Exo-Hydroxy-lO-Bornyl Group As an Efficient Ligand on the Sulfur Center Rev. Heteroat. Chem. 1992 6 202-217 Keywords allenic sulfoxide, a-sulfinylmaleate, a-sulfinylmaleimide, asymmetric synthesis, chiral unsaturated sulfoxides... 

The oxidation of heteroatoms and, in particular, the conversion of sulfides to asymmetric sulfoxides has continued to be a highly active field in biocatalysis. In particular, the diverse biotransformations at sulfur have received the majority of attention in the area of enzyme-mediated heteroatom oxidation. This is particularly due to the versatile applicability of sulfoxides as chiral auxiliaries in a variety of transformations coupled with facile protocols for the ultimate removal [187]. 

The enzymatic oxygenation process is of particular value as there is a significant difference in the formation rates of sulfoxides and sulfones. The initial conversion of sulfide to the optically active sulfoxide by an MO is usually very fast compared to the subsequent oxidation step to sulfone, upon which chirality is lost (Scheme 9.26). In many cases, over-oxidation to sulfone is not observed at all when employing MOs. 

Ketosulfoxides are subject to chelation control when reduced by DiBAlH in the presence of ZnCl2.141 This allows the use of chirality of the sulfoxide group to control the stereochemistry at the ketone carbonyl. 

To understand the interdependence of the creation of the two chiral centers relative to each other and to the sulfoxide, monosubstituted vinyl sulfoxides (S)-53 and (S)-54 were prepared and reduced with BH3-THF under the same conditions (Scheme 5.19). Both the 2- and 3-phenyl substituted substrates gave the chiral products 54 and 55 with complete stereo specificities dictated by the configuration of the starting sulfoxides. These results again were unexpected and indicated that both hydrogens were delivered solely directed by the chiral sulfoxide. This was not consistent with the mechanism in which the chirality of the initially formed chiral center at the 3-postion dictates the chirality of the subsequently formed chiral center at the 2-position. 

The propensity of S-S dications to undergo dealkylation was found to decrease in the order of methyl > ethyl > benzyl. This order of reactivity parallels the increase in the stability of the corresponding carbocations.94 Dealkylation of dication 77 affords thiosulfonium salt 78 in quantitative yield.95 Kinetic studies suggest SN1 mechanism of dealkylation. In addition, reaction of sulfoxide 79 with a substituent chiral at the a-carbon results in racemic amide 80 after hydrolysis. 

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