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

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.

Ready Access to [5,6,5]-Trioxa-spiro and Fused Ketals via Ag-Catalyzed Cascade Annulation of 4-Pentyn-1-ols and Aldehydes.

In this study, we unveil the versatility of 4-pentyn-1-ols as carbonyl surrogates for the unprecedented synthesis of diverse oxygen heterocycles, including [5,6,5]-bis-spiroketals (trioxadispiroketals) and [5,6,5]-furano-spiroketals related to bioactive natural products. These reactions commence with the π-activation-induced intramolecular hydroalkoxylation of 4-pentyn-1-ols, yielding cyclic enol ethers, which undergo subsequent three-component annulation with aldehydes in a [2+2+1+1] fashion, resulting in the formation of [5,6,5]-bis-spiroketals. Notably, the distinctive steric features of alkynyl alcohols, particularly those with a secondary or tertiary alcohol functionality, dictate divergent reaction pathways, leading to the formation of [5,6,5]-furano-spiroketals.

Brønsted Acid-Promoted Cyclodimerization of α,ß-Unsaturated γ-Ketoesters: Construction of Fused Pyrano-ketal-lactones and γ-Ylidene-butenolides.

Unprecedented MsOH-promoted diastereoselective cascade dimerization and intramolecular lactonization of readily accessible α,ß-unsaturated γ-ketoesters are presented. The results obtained in this work, control experiments, and density functional theory (DFT) calculations suggested that the initial enolization and E to Z isomerization/equilibration of olefin (C=C) of substrate α,ß-unsaturated γ-ketoesters give a Z-isomer preferentially over an E-isomer. Subsequently, the Z-isomer undergoes intermolecular annulation with α,ß-unsaturated γ-ketoesters via domino Michael addition/ketalization/lactonization steps to furnish fused tetracyclic pyrano-ketal-lactone. However, the Z-isomer prefers intramolecular trans-esterification in a competing pathway and gives bicyclic γ-ylidene-butenolide. The key features of this work include simple Brønsted acid catalysis, the formation of three bonds, two rings, and three contiguous stereogenic centers in a single step, DFT calculations, and the assignment of relative stereochemistry through X-ray diffraction (XRD) and two-dimensional (2D) nuclear magnetic resonance (NMR) analyses.