Stereoselective thiochromans

On treatment with a Lewis acid, a-(benzotriazolyl)methyl thioethers generate a-ihionium ions which can be trapped by styrenes in a [4 + 2] cationic cycloaddition to produce thiochromans 38. The reaction proceeds in high yield and allows good variation in substitution pattern. The stereoselectivity is variable, though often only one isomer is obtained and seldom more than two <01JOC5595>. 

Acetates of MBH adducts have also been established for the synthesis of sulfur-containing trisubstituted alkenes via a nucleophilic displacement protocol, in either S- 2 or S- 2 fashion with 5-centered nucleophiles, such as thio-lates, ° arenesulfinate and thiocyanate anions. Significantly, these reactions are highly stereoselective for both acrylonitrile/acrylate ester-derived MBH acetates, but with a reversed stereochemical directive effect, that is, acrylonitrile-derived MBH acetates afford ( )-sulfur-containing trisubstituted alkenes 336 as the sole product, while acrylate ester-derived MBH acetates afford (Z)-olefins 335 exclusively under the same reaction conditions. Both (Z)-and ( )-allyl sulfides have been stereoselectively obtained from MBH acetates in a one-pot with treatment with benzenethiol in the presence of catalytic amounts of 15% aqueous NaOH and TBAI in DM SO at room temperature (Scheme 3.146). ° The method has also been applied for the synthesis of (Z)-3-(4-methoxybenzylidene)thiochroman-4-one (337), a potent antifungal compound (Scheme 3.147). 

A closely related methodology was applied by Zhao et al. to the enantio-selective synthesis of tetrasubstituted thiochromanes on the basis of a domino thia-Michael-Knoevenagel reaction between 2-mercaptobenzaldehydes and benzylidenemalonates with the same quinine thiourea catalyst. Steric and electron effects were found to affect profoundly the stereoselectivities of the reaction. Thus, it was shown that the diastereoselectivity of the reaction... 

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