P-hydroxysulfoxides

Scheme 3.57 P-Hydroxysulfoxide ligands for addition of ZnEt2 to benzaldehyde.

To a solution of p-hydroxysulfoxide (3a) (1 mmol) in dichloromethane (20ml) at room temperature was added m-CPBA (1.1 eq) in dichloromethane (20ml). After 6h at room temperature, the reaction mixture was washed with a 5% aqueous solution of sodium hydroxide (20 ml) and then dried over sodium sulfate. After evaporation of the solvent the crude sulfone obtained in a 56-58% yield was used without further purification (m.p. 69°C). 

Solladie, G, Frechou, C, Hutt, J, Demailly, G, Stereospecihe hydroxylation of chiral allylic p-hydroxysulfoxides asymmetric synthesis of L-arabinitol, Bull. Soc. Chim. Fr., 827-836, 1987. 

The Sharpless epoxidation of allylic alcohols by hydroperoxides uses as mediator [45] or as catalyst [46] a chiral titanium complex obtained from the combination Ti(OPr )4/diethyl tartrate (DET) in 1 1 ratio. Kinetic resolution of P-hydroxysulfides was also observed, but without diastereoselectivity for the product P-hydroxysulfoxides [47]. We found that the Sharpless reagent deactivated by 1 equivalent of water allows the enantioselective oxidation of aryl methyl sulfides into sulfoxides to be performed with ee s up to 90% [4S-50]. The best reagent combination proved to be Ti(0Pr )4/DET/H20 = 1 2 1. Independently, Modena et al. obtained similar enantioselectivities with the combination Ti(OPr )4/DET in 1 4 ratio [51]. These two combinations are sometimes referred to as the Kagan reagent and the Modena reagent, respectively. They will be considered successively. 

Guanti established [4] that the LAH reduction of a-tolylthio-p-ketosulfoxides, prepared by direct acylation of the lithio-anion of optically pure (S)-(+)-p-tolyl p-tolylthiomethyl sufoxide was highly diastereoselective, yielding diastereoisomeric product alcohols in ratios up to >99 1 (4a 4b) (Scheme 4.3) [5]. The p-hydroxysulfoxide products (4a) and (4b) can be considered as protected a-hydroxyaldehydes indeed, the synthesis of enantiomerically pure (R)-(-)-a-methoxyphenylacetaldehyde (5) (and its (S )-(+) antipode) was demonstrated through application of a previously established procedure [6]. 

Epoxide enantiomers (10) and (11) were prepared in good yields (60-70%) and excellent enantioselectivity (>90% ee) from the P-hydroxysulfoxides (6) and (7), respectively (Scheme 4.6). 

A few comparisons of molecules which differ stereochemically are available. Aqueous-phase data on P-hydroxysulfoxides have been quoted which show that whereas the two racemic diastereomeric compounds display virtually identical liquid- and liquid-crystal-phase boundaries, they differ substantially in the temperature range of their crystal solubility boundaries [39]. In particular, the higher melting isomer displays the higher Krafft eutectic temperature. The situation is one in which the l drophilicity of the two isomers appears to be virtually identical—but their ability to pack into a crystal differs substantially as a result of their differences in shape. Molecular shape is very important to crystal thermodynamics. 

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