Construction of 1,3-Nonadjacent Stereogenic Centers Through Enantioselective Addition of α-Thioacetamides to α-Substituted Vinyl Sulfones Catalyzed by Chiral Strong Brønsted Base.

An enantioselective addition reaction for the construction of 1,3-nonadjacent stereogenic centers is developed by means of a chiral strong Brønsted base catalyst. The chiral sodium ureate catalyst efficiently promoted the reaction of α-thioacetamides as less acidic pronucleophiles with vinyl sulfones having a variety of α-substituents including aryl, alkyl and halo groups, and α-phenylacrylates, accomplishing the construction of various 1,3-nonadjacent stereogenic centers in highly diastereo- and enantioselective manners. This is a rare example of the construction of 1,3-nonadjacent stereogenic centers with less acidic pronucleophiles. In addition, the application of Michael acceptors having various types of α-substituents in a single catalyst system is achieved for the first time, demonstrating the utility of the present catalyst system for the construction of 1,3-nonadjacent stereogenic centers.

Formal Fluorinative Ring Opening of 2-Benzoylpyrrolidines Utilizing [1,2]-Phospha-Brook Rearrangement for Synthesis of 2-Aryl-3-fluoropiperidines.

A ring expansion of 2-benzoylpyrrolidines, which involves the formal fluorinative ring opening utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis and a subsequent intramolecular reductive amination, was developed. The operationally simple three-step protocol provides an efficient access to 2-aryl-3-fluoropiperidines. The methodology was further applied to the syntheses of azepanes and tetrahydroquinolines.