Danishefsky dimethyl-substituted

Two general approaches to aza-Diels-Alder reactions have been reported. One incorporates the requisite nitrogen atom into the 2rt component (imine), while the other incorporates the requisite nitrc en in the 4rt component (azadiene). Chiral copper Lewis acids have been used with success in both approaches. Jorgensen and coworkers reported enantioselective imino Diels-Alder reactions catalyzed by CuC104 MeCN in the presence of phosphino-oxazoline (287) or BINAP (290) (Scheme 17.64) [93]. Phosphino-oxazoline (287) proved to be the ligand of choice in the aza-Diels-Alder reaction of N-tosyl a-imino ester (142) with Danishefsky s diene (286), while BINAP (290) gave the highest selectivity when dimethyl-substituted Danishefsky s diene (289) was used. 

Reactions of enol silanes with (V,N-dimethyl(methylene)iminium salts occur under milder conditions than those of simple ketones because an initial enolization step is not required. The reaction is normally performed at room temperature, and aprotic solvents must be used to prevent hydrolysis of the enol silane. Danishefsky and coworkers, in their pioneering investigations of this reaction using TMS enol silanes and iminium iodide (30), have suggested the intermediacy of a silyloxonium salt (57), which loses a proton to give a 2-substituted enol silane (58) as its HI salt (Scheme 11). Subsequent hydrolysis of the enol silane during acid-base work-up affords the Mannich base (59). 

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