Reformatsky Reaction to Alkynyl N- tert-Butanesulfinyl Imines: Lewis Acid Controlled Stereodivergent Synthesis of ß-Alkynyl-ß-Amino Acids.

A highly diastereoselective Refortmatsky reaction to N- tert-butanesulfinyl propargylaldimines and ketimines is presented. The reaction proceeded with excellent yields and diastereoselectivities provided by the sulfinyl group in the presence of Me3Al. The use of TBSOTf as a Lewis acid promoter switched the sense of the stereoinduction. Thus, this methodology allowed the stereodivergent asymmetric synthesis of ß-alkynyl ß-amino acid derivatives, from the same sulfinyl configuration, by simply changing the Lewis acid promoter.

Cyclization cascades via N-amidyl radicals toward highly functionalized heterocyclic scaffolds.

The addition of a variety of radicals to the double bond of N-(arylsulfonyl)acrylamides can trigger cyclization/aryl migration/desulfonylation cascades via amidyl radical intermediates 2. Herein, we demonstrate the synthetic utility of these intermediates in subsequent C-C and C-X bond-forming events to rapidly build up molecular complexity. First, we describe a regioselective one-pot synthesis of CF3-, SCF3-, Ph2(O)P-, and N3-containing indolo[2,1-a]isoquinolin-6(5H)-ones from N-[(2-ethynyl)arylsulfonyl]acrylamides through a multi-step radical reaction cascade. The process involves the one-pot formation of four new bonds (one C-X, two C-C, and one C-N), a formal 1,4-aryl migration, and desulfonylation of the starting material. Second, we present a one-pot synthesis of 3,3-disubstituted-2-dihydropyridinones from N-(arylsulfonyl)acrylamides and 1,3-dicarbonyl compounds. In this case, a silver-catalyzed radical cascade process involving the sequential formation of two new C-C bonds and one C-N bond, a formal 1,4-aryl migration, and desulfonylation of the starting material explains the regioselective formation of densely functionalized heterocycles in a straightforward manner. Control experiments have unraveled the key intermediates as well as the sequence of individual steps involved in these transformations.