Asymmetric chiral sulfur-containing compounds

Asymmetric sulfinyl transfer reactions are of significant interest, since they can be applied to the synthesis of chiral sulfur-containing compounds, which are valuable synthons for pharmaceuticals and natural products [46]. Moreover, chiral sulfoxides are versatile chiral auxiliaries for asymmetric organic synthesis. A number of studies... 

Chiral Phosphorus and Sulfur-Containing Compounds in Asymmetric Synthesis. 

Many organosulfur compounds can be resolved into optically active forms (enantiomers) owing to the presence of a chiral (asymmetric) sulfur atom 5 important examples include sulfoxides and sulfonium salts. Chiral sulfoxides containing amino or carboxylic acid groups have been resolved by formation of the diastereoisomeric salts with d-camphor-10-sulfonic acid or d-brucine. The salts can then be separated by fractional crystallisation and the free optically isomeric sulfoxides liberated by acid hydrolysis. However, a more convenient synthetic procedure for the preparation of chiral sulfoxides of high optical purity is Andersen s method (see p. 30). 

Phosphorus-containing Ring Systems. - A range of new chiral oxazaphospholidine oxides 266 and 267 have been synthesised and used as catalysts in asymmetric reductions of ketones with diborane. Mannich-type cyclisation reactions of 5-amino-3-benzylthio-4-cyano(ethoxycarbonyl)pyrazoles with dichlorophenylphosphine and aromatic aldehydes in the presence of cation exchange resin have been used to prepare a number of 6-oxo-6-phospha-4,5,6-trihydroimidazolo[l,2-b]pyrazoles, e.g. 268. Some of these compounds have herbicidal activity and this report is typical of a number of similar ones in the Chinese literature. A number of metallocycles, e.g. 269, have been reported as products from reactions of transient zirconocene-benzyne intermediates with phosphaimines followed by sulfuration or selenation. ... 

The necessary criterion that an object not be superimposable on its mirror image can be met by a number of types of compounds in addition to those containing asymmetric carbon atoms, an important example being sulfoxides containing nonidentical substituents on sulfur. Sulfoxides are nonplanar, and there is a sufficient barrier to inversion at sulfur that the pyramidal sulfoxides maintain their configuration at room temperature. Unsymmetrical sulfoxides are therefore chiral and exist as enantiomers. Sulfonium salts with three nonidentical ligands are also chiral as a result of their pyramidal shape. Some examples of chiral derivatives of sulfur are given in Scheme 2.1. 

HPLC is one of the most universal methods for determining the enantiomeric composition of substances and mixtures in a short time frame. Its application is not restricted to molecules in which chirality is based on a quaternary carbon atom with four different substituents it can also be employed for compounds containing a chiral silicon, nitrogen, sulfur, or phosphorus atom. Likewise, asymmetric sulfoxides or aziridines, the chirality of which is based on a lone electron pair, can be separated. Chirality can also be traced back to helical structures, as in the case of polymers and proteins to the existence of atropiso-merism, the hindered rotation about a single bond, as observed, for example, in the case of binaphthol, or to spiro compounds. 

The asymmetric addition of phosphorus nucleophiles to imines provides direct access to phosphorus-containing chiral amines. While this chemistry is dominated by the use of phosphites and related compounds, a report by Duan outlines a successful protocol for the asymmetric addition of secondary phosphines to imines (Scheme 4.30) [81]. The reaction was catalyzed by a chiral palladium compound comprised of a palladium(II) center Ugated by a resolved pincer compound. A range of aryl and heteroaryl imines as well as several secondary phosphines were successfully used in this reaction. To aid in the isolation of the phosphines, the authors added elanental sulfur at the end of the P—C bond-fomung reaction. This chenustry provides access to a range of chiral N,P Ugands for metal centers that were previously challenging to prepare and isolate. 

Recently, macrocyclic chiral compounds of crown ether or cyclamen type have been attracting wide interest. These compounds contain numerous heteroatoms in their molecules (mainly oxygen, sulfur, and nitrogen) and can find practical applications, for example, as chiral selectors [69,70] and chiral NMR discriminating agents [71]. Asymmetric substitution of two carbon atoms in the ring of crown ether or cyclamen can lead to many different optically active compounds useful in various branches of supramolecular chemistry. Such substitution can be accomplished with appropriate starting compounds that are optically active, for example, amino acids and polyhydroxy alcohols. 

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