Enantioselective synthesis of isochromans and tetrahydroisoquinolines by C–H insertion of donor/donor carbenes. Issue 2 (27th November 2019)

• Record Type: Journal Article
• Authors: Nickerson, Leslie A.; Bergstrom, Benjamin D.; Gao, Mingchun; Shiue, Yuan-Shin; Laconsay, Croix J.; Culberson, Matthew R.; Knauss, Walker A.; Fettinger, James C.; Tantillo, Dean J.; Shaw, Jared T.
• Is Part Of: Chemical science. Volume 11:Issue 2(2020)
• Page Start: 494
• Page End: 498
• Publication Date: 2019-11-27
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c9sc05111b
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Six-membered ring oxygen and nitrogen heterocycles are formed stereoselectively by C–H insertion of donor/donor carbenes. Abstract : Reports of C–H insertions forming six-membered rings containing heteroatoms are rare due to Stevens rearrangements occurring after nucleophilic attack on the carbene by a heteroatom. Using donor/donor carbenes and Rh2 ( R -PTAD)4 as a catalyst, we have synthesized a collection of isochroman substrates in good yield, with excellent diastereo- and enantioselectivity, and no rearrangement products were observed. Furthermore, we report the first synthesis of six-membered rings containing nitrogen by C–H insertion to form tetrahydroisoquinolines. In one case, a Stevens rearrangement product was isolated at elevated temperature from a carbamate-protected amine substrate and computational evidence suggests formation through a free ylide not bound to rhodium.