Sulfinate, Andersen

Reaction of Grignard reagents with optically active sulfinate esters (150) is a particularly useful route to optically active sulfoxides and occurs with 100% inversion of configuration (Andersen et al., 1964). Substitution reactions of... 

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... 

Andersen (75,76), as well as Mislow (221), discovered that the ORD curves of alkyl aryl sulfoxides show a strong Cotton effect in the region below 250 nm. An extensive study by Mislow and his coworkers (47) led to the following empirical rules, correlating the sign of the Cotton effect with the absolute configurations of chiral dialkyl, alkyl aryl, and diaryl sulfoxides, as well as menthyl esters of aromatic sulfinic acids ... 

A quite general method of access to optically pure sulfoxides is due to Andersen [96-98] a menthyl sulfinate ester is reacted with a Grignard reagent. Both enantiomers of menthyl p-toluenesulfinate are commercially available. A large-scale preparation of (-)-menthyl (S)-p-toluenesulfinate as well as that of (7 )-(+)-methyl p-tolyl sulfoxide is described [99] by Solladi et al. Other related approaches are presented and discussed in [86]. 

A new class of chiral sulfinyl transfer reagents, much more reactive towards Grignard reagents than the Andersen menthyl sulfinate ester, have been introduced by Evans [102] and reacted with a wide range of nucleophiles to afford chiral sulfoxides, sulfinate esters or sulfinamides efficiently. These reagents are shown below ... 

In a competition experiment between chiral N-sulfinyl oxazolidinone and Andersen s menthyl sulfinate ester, it has been shown that the former is at least two orders of magnitude more reactive than the latter. This finding is being used to avoid some of the problems involved in sulfinate esters, related to the nature of the alkoxide leaving group in the nucleophilic substitution. 

A method that makes available aromatic and aliphatic aldehyde derived sulfin-imines 47, for the first time, was recently introduced by Davis and co-workers.23,36 This one-pot procedure entails treatment of the Andersen reagent 40 with LiHMDS to generate 44 which subsequently reacts with the lithium methoxide by-product to produce silyl sulfinamide anion 46. Reaction of 46 with the aldehyde in a Peterson-type olefination reaction affords the sulfinimine 47 in >96% ee. This method was highly effective for the preparation of arylidene sulfmamides 47 (R = aryl) which were usually obtained in 60-76% yield although the alkyl counterparts... 

Optically active sulfoxides are readily obtained from menthyl sulfinate by a Grignaid reaction. This reaction was originally proposed by Gilman and applied to optically active products by Andersen - this is a pure 5n2 reaction at sulfur with displacement of the menthoxy group by the Grignard. A great variety of sulfoxides have been prepared by this method " " other organometallics have also been used. A few examples are shown in Scheme 40. 

Chiral sulfoxides are conveniently synthesised by Andersen s method (1962), in which a chiral sulfinate (4) is treated with a Grignard reagent. The reaction involves a sulfinyl group transfer and occurs with complete stereochemical inversion at the sulfur atom... 

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. 

Scheme 2.2 highlights Andersen s initial study, in which nucleophilic attack by ethylmagnesium iodide on enantiomerically pure (5)-(—)-menthyl p-toluene sulfinate displaces the O-menthyl leaving group to yield 62% of (R)-(-i-)-ethyl p-tolyl sulfoxide (3). 

Andersen has described the synthesis of enantiomerically pure methyl alkyl and methyl aryl sulfoxides from chlolesteryl methane sulfinates [12]. The reaction of cholesterol and menthanesulfinyl chloride provides the crystalline, epimeric cholesteryl methEme sulfinates in quantitative yields (Scheme 2.5). Pure samples of the (J ) or (S) epimers can be obtained in very low yield (0.7% and 3.5%, respectively) by crystallization. 

More reeently, Whitesell has recently reported an improved method for the preparation of enantiomerically pure sulfinate esters (Scheme 2.11) [19]. As previously described, the (5)-(-)-menthyl p-toluene sulfinate diastereoisomer only is readily available in a pure, crystalline form using the Andersen procedure. Whitesell discovered that reaction of the ehiral auxiliary trans-2-phenylcyclohexanol (8) with an excess of alkyl or arene sulfinyl chloride afforded the appropriate sulfinate esters (9) and (10) in good yield and with better selectivities (up to 10 1) than those observed with (lf ,25,5f )-(-)-menthol ( 2 1). These diastereoisomers can be readily separated (R p-Tol (9a) = 62% yield, 98% de) by either crystallization or by chromatography, in contrast to the Andersen procedure. 

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). 

Andersen reported the preparation of the first enantiopure sulfoxide in the 1960s [105], This was achieved by nucleophilic displacement of a leaving group from a diastereomerically pure sulfinate ester. Despite obtaining high yields of enantiopure sulfoxides, the preparation was difficult and there was a limited availability of... 

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