Revealing the Role of Solvent in anti-Oxypalladation-Triggered Regiocontrolled Domino Reactions for the Synthesis of Benzazepine- and Tetrahydroquinoline-Containing Scaffolds: A Combined Computational and Experimental Study

被引：0

作者：

Gupta, Anish ^{[1
]}

Ranaut, Sheetal ^{[2
]}

Kooleri, Athira ^{[2
]}

Jandial, Tanvi ^{[1
]}

Rani, Neha ^{[2
]}

Bhuvanesh, Nattamai ^{[3
]}

Mazumder, Shivnath ^{[2
]}

Sridharan, Vellaisamy ^{[1
,4
]}

机构：

[1] Cent Univ Jammu, Dept Chem & Chem Sci, Jammu 181143, Jammu & Kashmir, India

[2] Indian Inst Technol Jammu, Dept Chem, Jammu 181221, Jammu & Kashmir, India

[3] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA

[4] Univ Hyderabad, Sch Chem, Hyderabad 500046, India

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2024年 / 89卷 / 18期

关键词：

MOLECULAR-ORBITAL METHODS; HIGHLY SUBSTITUTED FURANS; BASIS-SETS; INTRAMOLECULAR OXYPALLADATION; STEREOSELECTIVE-SYNTHESIS; EFFICIENT SYNTHESIS; TANDEM REACTION; ARYL HALIDES; CASCADE; CYCLIZATION;

D O I：

10.1021/acs.joc.4c01127

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Palladium-catalyzed regiocontrolled intramolecular oxypalladation-initiated cascades of multifunctional internal alkyne bearing an N-tosyl tether deliver functionalized benzazepine as an exclusive product via 6-endo-dig pathway in 1,4-dioxane solvent and tetrahydroquinoline scaffold as a major product via the 5-exo-dig pathway in the DMSO solvent. The role of the solvent in controlling the regioselectivity is still unknown which can be a major hurdle for further reaction development. Moreover, the reaction in DMSO suffered from having a mixture of products, and no exclusive formation of tetrahydroquinoline was achieved. Herein, we report a concerted computational and experimental study, revealing the role of the solvent in controlling the reaction outcome. DFT study revealed that the formation of the sigma-vinylpalladium intermediate is reversible for the 5-exo-dig pathway while it is irreversible for the 6-endo-dig mechanism in 1,4-dioxane and consequently, the 5-exo-dig pathway is difficult to proceed. In contrast, both the 5-exo-dig and 6-endo-dig pathways are irreversible in DMSO. We predicted an exclusive formation of isobenzofuranone-fused chromane via the 5-exo-dig pathway when the N-tosyl tether is replaced by the O-tether in the internal alkyne in DMSO. The experimental study confirms the theoretical hypothesis and provides a highly chemo-divergent approach for the synthesis of biologically significant chromane with a large substrate scope and up to 95% yield at room temperature.

引用

页码：13038 / 13058

页数：21