Development of Catalytic Asymmetric Intramolecular Cyclopropanation of α-Diazo-β-Keto Sulfones and Applications to Natural Product Synthesis

Abstract

The catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of a-diazo-b-keto sulfones developed in our laboratory and applications to the total synthesis of natural products are described. CAIMCP features (a) a wide applicability, not only to the preparation of bicyclo[n.1.0]alkanes and tricyclo[4.n.0.0]alkenes, but also to the enantioselective total synthesis of natural products, (b) the formation of highly crystalline products, which facilitate the production of enantiomerically pure synthetic intermediates, and (c) the generation of products with a variety of functionalities, such as cyclopropane, ketone, and sulfone, beneficial to the total synthesis of natural products.

Synthesis of Cyclopropanes via Hydrogen-Borrowing Catalysis

“…Traditional methods to make cyclopropanes are dominated by carbene-based strategies, including the Simmons–Smith reaction, , the use of free carbenes, , and diazo-derived carbenoids (Scheme B). , The Kulinkovich reaction and cycloisomerization strategies have also been employed for the construction of cyclopropanes in total synthesis. − A conceptually distinct classical approach for the synthesis of cyclopropanes is via the intramolecular nucleophilic displacement of a leaving group. This was exemplified by Perkin in 1884 and has formed the basis of other powerful transformations, such as the Corey–Chaykovsky reaction. − Related approaches have been employed for the synthesis of cyclopropanes in a variety of natural product targets. , …”

“…Traditional methods to make cyclopropanes are dominated by carbene-based strategies, 3 including the Simmons–Smith reaction, 4 , 5 the use of free carbenes, 6 , 7 and diazo-derived carbenoids ( Scheme 1 B). 8 , 9 The Kulinkovich reaction and cycloisomerization strategies have also been employed for the construction of cyclopropanes in total synthesis. 10 − 12 A conceptually distinct classical approach for the synthesis of cyclopropanes is via the intramolecular nucleophilic displacement of a leaving group.…”