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Enantioselective synthesis of isochromans and tetrahydroisoquinolines 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.

SUBMITTER: Nickerson LA

PROVIDER: S-EPMC7439777 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Enantioselective synthesis of isochromans and tetrahydroisoquinolines by C-H insertion of donor/donor carbenes.

Nickerson Leslie A LA Bergstrom Benjamin D BD Gao Mingchun M Shiue Yuan-Shin YS Laconsay Croix J CJ Culberson Matthew R MR Knauss Walker A WA Fettinger James C JC Tantillo Dean J DJ Shaw Jared T JT

Chemical science 20191113 2

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 ri ...[more]

PMID: 32874491

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