Sulfur chiral centers

Various chiral centers, such as the chiral carbon center, chiral nitrogen center, chiral phosphorous center, and chiral sulfur center are depicted in Figure 12. 

This section surveys the most important reactions of chiral organo-sulfur compounds. Some of these were touched on in the previous sections. For the sake of convenience, a variety of reactions occurring at the chiral sulfur center are divided into three main types of reactions racemization, nucleophilic substitution reactions, and electrophilic reactions. 

Dialkylamino-aryloxosulfonium alkylides may be employed for enantioselective epoxidation if the ylide with its chiral sulfur center is resolved into its enantiomeric form, " An enantioselective oxirane is obtained by means of a chiral phase-transfer catalyzed procedure with dimethylsulfonium methylide. The utilization of arsonium ylides was reported some time ago. ° A highly stereoselective synthesis of trans-epoxides with triphenylarsonium ethylide has recently been described.Optically active arsonium ylide has been used in the asymmetric synthesis of diaryloxiranes. ... 

J. D. Morrison and J. W. ScoXt, Asymmetric Synthesis, Vol. 4, The Chiral Carbon Pool and Chiral Sulfur, Nitrogen, Phosphorus, and Silicon Centers, Academic Press, Inc., Odando, Fla., 1984. 

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 behavior of chiral phenyl /-butyl sulfoxide 219 and a-phenyl-ethyl phenyl sulfoxide 220 is completely different in strongly acidic media and in the presence of halide ions. Two reactions were found (266) to occur in parallel. One results in the loss of optical activity, and the second leads to the decomposition of the sulfoxide. It was observed that the racemization process is not accompanied by [ 0] oxygen exchange. In the case of sulfoxide 220 the complete loss of optical activity at chiral sulfur is accompanied by partial racemization at the chiral carbon center. These results are consistent with a sulfenic acid-ion-pair mechanism formulated by Modena and co-workers (266) as follows (it is obvious that the formation of achiral sulfenic acid is responsible for racemization). 

In the last two decades optically active sulfur compounds have found wide application in asymmetric synthesis. This is mainly because organic sulfur compounds are quite readily available in optically active form. Moreover, the chiral sulfur groupings that induce optical activity can be removed from the molecule easily, under fairly mild conditions, thus presenting an additional advantage in the asymmetric synthesis of chiral compounds. This section deals with reactions in which asymmetric induction in transfer of chirality from sulfur to other centers was observed. This subject has been treated only in a cursory manner in recent reviews on asymmetric synthesis (290-292). 

The most numerous group of asymmetric syntheses includes reactions of chiral sulfur compounds leading to diastereomeric systems as a result of the generation of a new chiral center and the preserva-... 

Organosulfur chemistry is presently a particularly dynamic subject area. The stereochemical aspects of this field are surveyed by M. Mikojajczyk and J. Drabowicz. in the fifth chapter, entitled Qural Organosulfur Compounds. The synthesis, resolution, and application of a wide range of chiral sulfur compounds are described as are the determination of absolute configuration and of enantiomeric purity of these substances. A discussion of the dynamic stereochemistry of chiral sulfur compounds including racemization processes follows. Finally, nucleophilic substitution on and reaction of such compounds with electrophiles, their use in asymmetric synthesis, and asymmetric induction in the transfer of chirality from sulfur to other centers is discussed in a chapter that should be of interest to chemists in several disciplines, in particular synthetic and natural product chemistry. 

The chirality at sulfur in the sulfinylallenes 1 is lost on prolonged standing. The racemization of the sulfur center must be due to an equilibration between the propynylsulfenate and the sulfinylallene, which racemizes the sulfur center but does not affect the stereochemical integrity of the allene axial chirality. 

Pradilla et al. [140] have recently produced a nice paper showing that enan-tiopure hydroxy 2-p-tolylsulfinyl butadienes 158 (Scheme 78) undergo a highly face-selective Diels-Alder cycloaddition with AT-phenyl maleimide and phenyl-triazolidine dione, presumably controlled by the chiral sulfur atom (dienophile approach from the upper face of diene). Complementary 7r-facial selectivity (dienophile approach from the bottom face of diene) is displayed by related enantiopure sulfonyldienes 158 (Scheme 78). The authors suggest that the behavior of 158 is a consequence of the predominant influence of the chiral sulfur with respect to the hydroxylic carbon (the only chiral center in 158 ) on the stereochemical course of the cycloadditions. According to their explanation, dienes will adopt conformations similar to those depicted in Scheme 78, with the chiral centers employing their stereochemistry to maximum effect due to 1,3-allylic strain (which is considered as the main directing effect of these cycload-... 

Moreover, N-sulfinyl oxazolidinones have been shown to be good intermediates for the synthesis of chiral sulfinate esters and sulfinamides with excellent ee. In all cases, the absolute configuration of the sulfoxide obtained is in agreement with the fact that nucleophilic displacement occurs with inversion of configuration at the sulfur center in the starting /V-sulfinyl oxazolidinone. 

With regard to isomerizations of double bonds, sulfinyl enynes gave unexpected results when submitted to PKR. These chiral substrates were thought to give high asymmetric inductions due to the proximity of the chiral sulfur atoms to the reaction centers. Surprisingly, both cis and trans ferf-butyl vinyl sulfoxides (237-238) were transformed into the same PK diastereoisomer 239 with high ee and moderate yields (Scheme 67) [103,104]. 

A recent report details absolute stereochemical control at levels of up to 75 25 in ene reactions, although typical levels are lower35. This selenium reagent has two identical, chiral sulfur atoms and it is these stereogenic centers that provide for reagent-based control of absolute stereochemistry. 

Asymmetric [4 + 2] cycloadditions of an optically active diene, or dienophile with chiral sulfinyl groups, with a quaternary sulfur center have succeeded in the LiC104-CH2CI2 medium. When chiral dienophile 66 and CP were subjected to cyclization, neither the endotexo ratio nor the enantiofacial selectivity of endo adducts was high [83], In the reaction of chiral diene 67 with MA, the best catalyst was LiC104-CH2CI2 this gave only endo isomers endo-6Sa and endo-6Sb in 70 % yield in the ratio of 96 4, presumably via TS-2 (Sch. 35) [84]. 

The rapid development of chiral phosphine derivatives of ferrocene was undoubtedly due to their application in catalysis. In contrast, chiral sulfur compounds from lithiated iV,iV-dimethyl-l-ferrocenylethylamine were only prepared about 15 years later [140], For the synthesis of such derivatives, the lithiated amine is treated with disulfides as shown in Fig. 4-24, top (and analogously, diselenides [141]). The sulfides obtained are easily oxidized by peracids or NaI04 to the corresponding sulfoxides. As sulfur becomes a new center of chirality by the oxidation, diastereoisomeric sulfoxides are formed in ratios depending on the oxidant [140]. If chiral oxaziridines [106, 142] are used as oxidizing agents, the diastereoisomeric ratio is appreciably... 

There are several efficient methods available for the synthesis of homochiral sulfoxides [3], such as asymmetric oxidation, optical resolution (chemical or bio-catalytic) and nucleophilic substitution on chiral sulfinates (the Andersen synthesis). The asymmetric oxidation process, in particular, has received much attention recently. The first practical example of asymmetric oxidation based on a modified Sharpless epoxidation reagent was first reported by Kagan [4] and Modena [5] independently. With further improvement on the oxidant and the chiral ligand, chiral sulfoxides of >95% ee can be routinely prepared by these asymmetric oxidation methods. Nonetheless, of these methods, the Andersen synthesis [6] is still one of the most widely used and reliable synthetic route to homochiral sulfoxides. Clean inversion takes place at the stereogenic sulfur center of the sulfinate in the Andersen synthesis. Therefore, the key advantage of the Andersen approach is that the absolute configuration of the resulting sulfoxide is well defined provided the absolute stereochemistry of the sulfinate is known. 

The adducts formed in these cases are the analogous dihydrothiazine imines 2. Symmetrical and unsymmetrical sulfur diimides are available, and both can act as heterodienophiles. In adducts 1 and 2 the sulfur center is chiral, and the implications of this fact will be discussed in some of the following sections. 

Other elements can produce chiral centers besides carbon, although their importance in industry and in health studies is not as great. The sulfur atom can produce chiral centers for example the sulfoxides, sulfoximides, sulphonates and the sulfonium ion. An example of a chiral sulfur atom is given by the following sulfoxide structure. 

Although stereogenic sulfur centers had been used as the source of chiral auxiliaries and hgands [190-195], organocatalysts incorporating chirality solely through the sulfur atom had been almost overlooked in the hterature before the development of... 

A subsequent study by Jprgensen et al. also demonstrated the enantioselective a-sulfenylation of (S-dicarbonyl compounds 420 using l-alkylsulfanyl[l,2,4]triazole derivatives 419 in the presence of a catalytic amount of cinchona alkaloid derivative 421. The use of cyclic (S-dicarbonyl compounds ensured the introduction of a quaternary sulfur center however, the observed enantioselectivity was modest in 51-89%. In 2009, Zhu and co-workers reported that a chiral a,a-diaryl prolinol 424 efficiently catalyzed the enantioselective sulfenylation of (S-ketoesters 420 using N-(phenylthio)phthalimide 423 as a sulfur electrophile. The absence of racemizable C—H bonds led to the optically enriched a-sulfenylated products 425 in excellent enantio-selectivities. In 2010, Fu developed a method for catalytic asymmetric 7-sulfenylation of carbonyl compounds using 2,3-allenoates 426 in the presence of a chiral bisphos-phine, TangPhos 427, and a bulky carboxylic acid 428. ... 

Tricoordmate sulfur compounds are chiral when sulfur bears three different sub stituents The rate of pyramidal inversion at sulfur is rather slow The most common compounds m which sulfur is a chirality center are sulfoxides such as... 

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