Nucleophilic aliphatic substitution alkyl sulfonates

Another catalytic application of chiral ketene enolates to [4 + 2]-type cydizations was the discovery of their use in the diastereoselective and enantioselective syntheses of disubstituted thiazinone. Nelson and coworkers described the cyclocondensations of acid chlorides and a-amido sulfones as effective surrogates for asymmetric Mannich addition reactions in the presence of catalytic system composed of O-TM S quinine lc or O-TMS quinidine Id (20mol%), LiC104, and DIPEA. These reactions provided chiral Mannich adducts masked as cis-4,5 -disubstituted thiazinone heterocycles S. It was noteworthy that the in situ formation of enolizable N-thioacyl imine electrophiles, which could be trapped by the nucleophilic ketene enolates, was crucial to the success of this reaction. As summarized in Table 10.2, the cinchona-catalyzed ketene-N-thioacyl-imine cycloadditions were generally effective for a variety of alkyl-substituted ketenes and aliphatic imine electrophiles (>95%ee, >95%cis trans) [12]. 

The C-X bond of alkyl halides and sulfonate esters is polarized such that the carbon has a positive dipole. Halides and sulfonate anions are good leaving groups. Nucleophiles attack primary and secondary alkyl halides, displacing the leaving group in what is known as aliphatic, bimolecular nucleophilic substitution, the Sn2 reaction. The 8 2 reaction follows second-order kinetics, has a transition state rather than an intermediate, and proceeds via back-side attack of the nucleophile on the halide and inversion of configuration. 

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