Andersen procedure sulfoxides

The Andersen procedure for the synthesis of ENANTIOMERICALLY ENRICHED, CHIRAL SULFOXIDES 41... 

The Andersen Procedure for the Synthesis of Enantiomerically Enriched, Chiral Sulfoxides... 

Johnson was able to overcome the synthetic limitations of the Andersen procedure by inducing the displacement of aryl groups from diaryl or alkyl aryl sulfoxides with either alkyllithium or alkyl sodium reagents as a general approach to optically active, unsymmetrical dialkyl sulfoxides (Scheme 2.4, Table 2.1) [13]. 

Another drawback of the classical Andersen procedure is that it allows for isolation of diastereoisomerically pure (5)-(-)-menthyl p-toluene sulhnate in a poor 30% yield. An early improvement pioneered by Hebrandson employed the known racemization of sulfoxides by HCl in an epimerization/equilibration technique to increase the yield of (5)-(-)-menthyl p-toluene sulhnate to 90% from the initial (R) and (5) diastereoisomeric mixture [14]. This adaptation has been described in detail by Solladie and the proposed epimerization/equilibration is... 

This reaction is more stereoselective than the corresponding synthesis of menthyl sulfinate diastereoisomers in the Andersen procedure, allowing for easier fractional crystallization. Optically active (/ )-(+)-methyl phenyl sulfoxide (13) is obtained on reaction of (lf ,2S)-(12) with methyllithium (Scheme 2.14). 

The A -sulfinyloxazolidinones have also been demonstrated to be highly efficient reagents for the synthesis of dialkyl sulfoxides in high yields and with excellent enantioselectivities as discussed, this class of sulfoxide has proved to be inaccessible through the Andersen procedure. Examples are highlighted in Scheme 2.17 and Table 2.6 for A-sulfinyloxazolidinone (16). 

In conclusion, Snyder and Benson s approach allows the synthesis of enantiomerically pure dialkyl and alkyl aryl sulfoxides in good yields and with excellent enantioselectivities. Both enantiomers are accessible by reversing the order of organometallic displacement or by employing the (15,2J )-(+)-ephedrine enantiomer. The only limitations are observed in the synthesis of t-butyl phenyl and aryl phenyl sulfoxides. However aryl phenyl sulfoxides are accessible by the Andersen procedure, and t-butyl phenyl sulfoxides by an approach to chiral sulfoxides developed by Kagan, described below. 

The procedure most commonly used for the stereospecific preparation of optically active sulfoximides involves the reaction of optically active sulfoxides with arylsulfonyl azides in the presence of copper (98,118,131,178,179). This reaction occurs with retention of configuration at sulfur and with high stereospecificity. The stereospecific sulfoxide-sulfoximide conversion is a key reaction in the stereospecific sulfoxide-sulfimide-sulfoxiraide set of interconversions carried out by Cram and co-workers (98) and shown in Scheme 9. A similar cycle of interconversions studied independently by Andersen and co-workers (179) was used to determine the stereochemical course of the sulfoxide-sulfoximide transformation (see Scheme 10). 

Both enantiomers of methyl p-tolyl sulfoxide are available from the above procedure by selection of the appropriate diethyl tartrate. This procedure describes the preparation of (S)-(-)-methyl p-tolyl sulfoxide which is not easy to prepare by the Andersen method " using (+)-raenthol. 

The reaction of 2 equiv of /V,/V-dimethylhydrazone 97, obtained by standard procedure, with 2 equiv of n-BuLi gave the corresponding a-lithioderivative, which on reaction with methanesulfinates 87 (R = Me) and 88 (R = Me) yielded o.p. sulfoxides 985 and 98R, respectively, in high yield. The configurational assignment of the a-sulfinyl hydrazone obtained was made assuming that the condensation step occurs with complete inversion of configuration at the sulfinyl sulfur, as is the case for many Andersen-type reactions. 

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). 

Following the pioneering work of Gilman [1], Andersen, in 1962, reported the first synthesis of an optically active sulfoxide of high enantiomeric purity through nucleophilic displacement at sulfur [2]. The key step in Andersen s procedure... 

---