A Catalytic, Enantioselective Sulfamate Tethered Aza-Michael Cyclization

We show the first examples of enantioselective cyclization reactions of tethered sulfamates onto pendant α,β-unsaturated esters, ketones, and thioesters. This reaction is promoted by a new chiral bifunctional guanidine catalyst and is operationally very simple. Product is formed by simply stirring substrate and catalyst in methylene chloride at room temperature without any special precautions to exclude air or ambient moisture. A variety of primary sulfamates and sulfamides were examined, and, in many cases, products were delivered in excellent yields and enantiomeric ratios. With secondary sulfamates, kinetic resolutions were possible. With these kinetic resolutions, rationally varying reaction conditions allowed for either high enantioenrichment of the racemic sulfamate substrates or for cyclizations with good yields, enantiomeric ratios, and diastereoselectivities. The product oxathiazinanes were very useful chiral intermediates and could be transformed into an array of enantioenriched small molecules.