Divergent Synthesis of Oxepino-Phthalides and [5,5]-Oxaspirolactones through [2 + 2 + 2]- and [2 + 3]-Annulation of Alkynyl Alcohols with α-Ynone-Esters

Digambar A Kambale; Balasaheb R Borade; Ramavath Vinodkumar; Ravindar Kontham

doi:10.1021/acs.joc.3c01301

Divergent Synthesis of Oxepino-Phthalides and [5,5]-Oxaspirolactones through [2 + 2 + 2]- and [2 + 3]-Annulation of Alkynyl Alcohols with α-Ynone-Esters

J Org Chem. 2023 Sep 1;88(17):12597-12612. doi: 10.1021/acs.joc.3c01301. Epub 2023 Aug 23.

Authors

Digambar A Kambale^{1

2}, Balasaheb R Borade^{1

2}, Ramavath Vinodkumar^{1

2}, Ravindar Kontham^{1

2}

Affiliations

¹ Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune411008, India.
² Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

PMID: 37611259
DOI: 10.1021/acs.joc.3c01301

Abstract

Unmasking the synthetic potential of alkyne functional group of alkynyl alcohols as surrogates of carbonyl compounds, herein we present the first Brønsted acid (TfOH)-catalyzed [2 + 2 + 2]-annulation of 4-pentyn-1-ols (possessing terminal alkyne) with α-ynone-esters to access tricyclic tetrahydro-oxepino-phthalides. Besides, an unprecedented synthesis of α-acetoaryl or α-alkynyl [5,5]-oxaspirolactones has been demonstrated by employing 4-pentyn-1-ols (possessing an internal alkyne) as an annulation partner, which proceeds through a divergent [2 + 3]-annulation pathway.