Andersen reagent

A -sulfinyl chiral auxiliaries have been used to prepare enantiopure tetrahydro-P-carbolines and tetrahydroisoquinolines in good yields under mild reaction conditions. Both enantiomers of V-p-toluenesulfinyltryptamine 46 could be readily prepared from the commercially available Andersen reagents.Compound 46 reacted with various aliphatic aldehydes in the presence of camphorsulfonic acid at -78 °C to give the A-sulfinyl tetrahydro-P-carbolines 47 in good yields. The major diastereomers were obtained after a single crystallization. Removal of the sulfinyl auxiliaries under mildly acidic conditions produced the tetrahydro-P-carbolines 48 as single enantiomers. 

Enantiopure sulfinimines 43 were prepared for the first time by Cinquini and co-workers from the commercially available Andersen reagent, (lR,2S,5R)-(-)-menthyl (S)-p-toluenesulfinate (40) or (lS,2/ ,5S)-(+)-menthyl (R)-p-toluenesulfi-... 

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... 

Reduction of (R)-(-)-N-[ 1 -(triethoxymethyl)ethylidene]-p-toluenesulfinamide (115), prepared by addition of MeLi to triethoxyacetonitrile followed by the Andersen reagent 40, gave a 95% yield of 116 as a single diastereoisomer on... 

After their introduction [73] as imine auxiliaries [74], the use of chiral p-toluenesulfinylimines 81 was pioneered by Davis (Scheme 11.12) [24, 26], The most facile and widely used synthesis of the parent sulfonamide involves the Andersen reagent 83 [75], both enantiomers of which are commercially available. Treatment of 83 with Li HMDS followed by aqueous workup gives optically active primary sulfmamide 84. This amide participates in condensation reactions with aldehydes or ketones under mild conditions to give a diverse array of N-sulfinyl imines 81 [24, 26, 76],... 

Further utility of the Andersen sulphoxides synthesis is demonstrated by the preparation of optically active unsaturated sulphoxides which were first prepared by Stirling and coworkers359 from sulphinate 276 and the appropriate vinylic Grignard reagents. Later on, Posner and Tang360 prepared in a similar way a series of ( )-l-alkenyl p-tolyl sulphoxides. Posner s group accomplished also the synthesis of (+)-(S)-2-(p-tolylsulphinyl)-2-cyclopentenone 287, which is a key compound in the chiral synthesis of various natural products361 (equation 159). 

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 most important and widely used approach to chiral sulfoxides is the method developed by Andersen (5) based on the reaction between the diastereomerically pure (or strongly enriched in one dia-stereomer) menthyl arenesulfinates and Grignard reagents. The first stereospecific synthesis of optically active (+H7 )-ethyl p-tolyl sulfoxide 22 was accomplished in 1962 by Andersen (75) from (-)-(iS)-menthyl p-toluenesulfmate 45 and ethylmagnesium iodide. 

An alternative stereospecific synthesis of chiral sulfimides reported by Nudelman (137) consists of the reaction of the diastereomeric menthyl p-toluenesulfinimidoates 90 with Gri ard reagents giving the optically active sulfimide 91. This reaction, like the Andersen synthesis of chiral sulfoxides, proceeds with inversion of configura-... 

In addition to routes involving resolution and asymmetric synthesis, optically active sulfonium salts have been prepared in a stereospecific way by Andersen (158,159). Thus, synthesis of the optically active dialkyl-p-tolylsulfonium salts 114 from the optically active ethoxy-sulfonium salt 115 was accomplished by the addition of alkyl Grig-nard or dialkylcadmium reagents. This reaction occurs with inversion... 

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 ... 

However, the 0,01-dimethyl octal one 129 and the tricyclic enone 132 behaved differently. Marshall and Andersen (45) obtained from 129 a mixture of isomers 130 and 131 (54% axial and 46% equatorial, when R=isopropyl and 82% axial and 17% equatorial when R=methyl) while Spencer and collaborators (46) isolated a =1 1 mixture of 133 and 134 from 132. By comparison with enones 127 which have an angular methyl group, the replacement of that group for a hydrogen atom in 129 and 132 must have eased the approach of the reagent on the top face to give products 131 and 134 with the equatorial alkyl group via a boat-like transition state. 

The reaction of organometallic reagents such as Grignard reagents or cuprates with chiral menthyl sulfinates57-63,64. known as the Andersen reaction65, yields optically active sulfoxides. 

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... 

The early observations of an aryl-aryl coupling were made during the studies of the reaction of a diarylsulfoxide with an organometallic reagent in the case of simple non-activated aromatic systems. Andersen et al described the formation of biphenyl (4) in good yields upon treatment of diphenylsulfoxide (106) with phenyllithium. ... 

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. 

Previously, Andersen et al. had attempted to prepare sulfuranes from the reactions of diaryl sulfoxides with aryl Grignard reagents and aryl lithium agents. They reported that the reactions give initially the corresponding triaryl sulfoni-um salts, from which two pathways, namely the formation of tetraaryl sulfuranes and the formation of benzyne, take place simultaneously, on the basis that they obtained diaryl sulfides and biaryls derived from benzyne, as shown in Scheme 7 [37]. 

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