Total Synthesis of Alanense A through an Intramolecular Friedel-Crafts Alkylation

Kosho Makino; Rio Fukuda; Shunsuke Sueki; Masahiro Anada

doi:10.1021/acs.joc.3c02481

Total Synthesis of Alanense A through an Intramolecular Friedel-Crafts Alkylation

J Org Chem. 2024 Feb 2;89(3):2050-2054. doi: 10.1021/acs.joc.3c02481. Epub 2024 Jan 19.

Authors

Kosho Makino^{1

2}, Rio Fukuda¹, Shunsuke Sueki^{1

2}, Masahiro Anada^{1

2}

Affiliations

¹ Faculty of Pharmacy, Musashino University, Nishitokyo, Tokyo 202-8585, Japan.
² Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo, Tokyo 202-8585, Japan.

PMID: 38241043
DOI: 10.1021/acs.joc.3c02481

Abstract

The first total synthesis of cadinane sesquiterpenoid alanense A, in which an intramolecular dehydrative Friedel-Crafts alkylation of 2,5-diaryl-2-pentanol is incorporated as a key step, has been achieved. The combinatorial use of p-TsOH·H₂O as a catalyst and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent provides 1,1-disubstituted tetrahydronaphthalene in 97% yield. It was also found that the combination of p-TsOH and HFIP is effective for the removal of phenolic MOM ether.