Asymmetric Synthesis of a-Substituted Sulfonamides and Sulfonates

Sulfonamides are known to be versatile antibiotics since the discovery of the antibacterial activity of streptozone and sulfachrysoidine by Domagk et al. [87]. Among the very few efficient methods reported for their asymmetric synthesis. 

Davis et al. [88] described the asymmetric synthesis of a-substituted primary sulfonamides involving the diastereoselective a-alkylation of N-sulfonylcamphor-imine dianions, while Huart and Ghosez reported an enantioselective synthesis of bicyclic cyclopentenones via a stereoselective 1,4-addition of metallated enan-tiopure sulfonamides to cyclic enones [89]. 

In view of this background, we developed a new chiral auxiliary to allow for the first time the efficient asymmetric a-alkylation of sulfonamides [90]. After testing some amine auxiliaries mainly based on proline, which did not show high diastereoselectivities, we synthesized the 4-biphenyl-substituted 2,2-dimethyl-l,3-dioxan-5-amine 108 as a new auxiliary. The racemate obtained according to Erlenmeyer s phenylserine synthesis was resolved with tartaric acid to give both enantiomers. 

Method A cone. HCI, retlux, 3 d Method B H0SO4, CHCI3, retlux, 1 d 

In summary, with the novel reactions described, the door was opened to a rich new chemistry of optically active sulfonamides, sulfonates, and sultones. 

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