Chiral sulfinyl auxiliaries

Stereoselective P additions have also been controlled by the introduction of chiral sulfinyl auxiliaries at the a position of alkenes. Several advantages of sul-finyl auxiliaries are pointed out. The use of bulky substituents on the chiral sulfoxide functions to shield one face of the P position of the alkene, allowing for control of radical addition. The dipole of the sulfoxide can be used to control ro-tamer populations with and without Lewis acids. In the absence of a chelating Lewis acid, dipole-dipole repulsion orients the sulfoxide and carbonyl groups in an anti conformation. On the other hand, bidentate Lewis acids can chelate these two Lewis basic functionalities and keep them oriented in a syn conformation. Finally, the sulfinyl group is easily removed or chemically transformed into other functionality. 

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. 

A wide variety of chiral sulfinyl substituents have been employed as chiral auxiliaries on both dienes162 and dienophiles163 in asymmetric Diels-Alder reactions. Carreno and colleagues164, for example, used Diels-Alder reactions of (Ss)-2-(p-tolylsulfinyl)-1,4-naphthoquinone (249) to separate racemic mixtures of a wide variety of diene ena-tiomers 250a and 250b via kinetic resolution and to obtain enantiomerically enriched... 

Chiral a-sulfinyl dimethylhydrazones form stabilized carbanions that can be used in enantioselective aldol reactions. A typical example is shown in equation (21). Removal of the chiral sulfur auxiliary is accomplished by reductive desulfurization. Under these conditions recovery and reuse of the sulfur moiety is impossible. Synthetic and optical yields reported for these aldol reactions are modest in most cases. However, in a direct comparison to the SAMpMaMP methodology, Annunziata has prepared (-)-(/ )-[6]-gingerol in 60% finders prior synthesis had yielded this aldol product in 36% ee. ... 

It has been shown that the sulfinyl group present as chiral auxiliary either in dienophiles or in dienes is very useful for controlling the enantio- and diastereofacial selectivity in the asymmetric Diels-Alder reaction [43]. A wide variety of enantiomerically pure cyclohexadienedicarboxylates has been produced by cycloaddition of the sulfinylmaleate 39 with several dienes under catalyzed... 

Chiral phosphoryl and sulfinyl groups are known as efficient auxiliaries in asymmetric synthesis. As reported below, their asymmetric induction in the a-posi-tion has been used to prepare chiral non-racemic organophosphorus compounds a-substituted by a sulfur function. Such compounds can also be obtained from their a-hydroxy analogues by OH-4 SR stereoselective transformation. 

The use of dimethyl (R)s-2-(10-isobornylsulfinyl)maleate (87) as a chiral synthetic equivalent of dimethyl acetylenedicarboxylate had several limitations arising from (i) the non-trivial preparation of the chiral auxiliary (10-mer-captoisoborneol) required to produce the dienophile, (ii) the low stereoselectivity observed in the synthesis of the thioether used as precursor of the sulfinyl reagent, and (iii) the lack of differentiation of the two ester groups present in the molecule. In order to avoid symmetrization, selective monodemethylation and further re-esterification were required as previous steps of desulfinylation (see... 

In a broad program of using chiral oxazolidinones in asymmetric synthesis,100 Evans s group published a paper in 1992 on the synthesis and utilization of fV-sulfinyl oxazolidinones as new sulfinylating agent.87 Two chiral auxiliaries were used in the study oxazolidinones derived from (4R, 5S)-norephedrine 74101 and (45)-phenylalanine 75.102 The corresponding fV-sulfinyl oxazolidinones 77 and 78 were obtained either by sulfmylation of the metallated oxazolidinone or by oxidation of the derived N-sulfenamides (Table 15). 

While high stereoselection has been achieved in radical reactions which occur in a-position146 to a center substituted with a chiral auxiliary, diastereofacial control in the addition of achiral radicals to the P carbon is, in general, difficult to achieve.147 In connection with this, Toru et al. reported extremely high P-stereoselection in the addition of tertiary, secondary, and even primary alkyl radicals to chiral a-sulfinyl cyclopentanones in 1993.148 The effectiveness of the diastereoselective addition of achiral radicals has been shown to depend on the size of the substituent at the sulfmyl sulfur. Bulky chiral arylsulfmyl groups show excellent diastereoselectivi-ties (> 98 < 2). 

By using chiral auxiliary groups derived from phenylmenthol or camphor, Lewis acid catalyzed Diels-Alder reactions gave an easy access to enantiomerically pure carbamate alcohols38,39. For example, the enantiomerically pure cycloadduct from cyclohexadiene and chiral IV-sulfinyl carbamate could be transformed into the bicyelic carbamate with complete transfer of chirality. 

The sulfinyl group is a useful temporary chiral auxiliary for the activation of a carbon carbon double bond towards nucleophilic addition as both enantiomers of a,//-unsaturated vinyl sulfoxides are available in enantiomerically pure form91. Both intermolecular and intramolecular conjugate additions of V-nucleophiles have been investigated. 

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... 

Asymmetric a-alkylation of amines was achieved applying an immobilized chiral sulfonamide (Scheme 12.29) [13, 40]. To synthesize auxiliary 76, a tertiary alcohol (73) was converted into Grignard reagent 74. Addition of sulfur dioxide and subsequent chlorination furnished the sulfinyl chloride 75. Reaction with (S)-2-amino-l,l,2-triphenylethanol, followed by reduction, hydroboration and... 

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