Disclosing Polycyclic Heterocycles: Synthesis of Furothienopyran and Pyranothienopyran Derivatives by Palladium Iodide Catalyzed Carbonylative Double Cyclization

Abstract

Polycyclic heterocyclic derivatives have been synthesized in one step by a carbonylative double cyclization approach starting from readily available starting materials. The method is based on a regioselective 6‐endo‐dig heterocyclization – cyclocarbonylation sequence catalyzed by the PdI2/KI catalytic system under oxidative conditions, with CO (5–10 atm) as the carbonylating agent and O2 (from air, 35–70 atm) as the external oxidant and formation of water as benign coproduct. Starting from thiophenecarboxylic acids bearing an ω‐hydroxyalkynyl substituent in vicinal position, previously unknown 1H‐furo[3,4‐b]thieno[3,2‐d]pyran‐1,5(3H)‐diones, 4H‐furo[3,4‐b]thieno[2,3‐d]pyran‐4,8(6H)‐diones, 3,4‐dihydro‐1H,6H‐pyrano[4,3‐b]thieno[3,2‐d]pyran‐1,6‐diones, and 6,7‐dihydro‐4H,9H‐pyrano[4,3‐b]thieno[2,3‐d]pyran‐4,9‐diones were obtained in 45–86% yields over 21 examples. The structures of two representative products have been confirmed by X‐ray diffraction analysis.

An Overview of Catalytic Carbonylative Double Cyclization Reactions

“…In fact, these substrates first underwent PdI 2 -catalyzed oxidative carbonylation of the primary amino group to give the corresponding urea [74,75], which then reacted through O-6-endo-dig cyclization from the ureidic carbonyl group followed by two successive cyclocarbonylations to yield the final product (Scheme 23) [73]. More recently, we studied the reactivity of thiophenecarboxylic acids having an ωhydroxyalkynyl substituent in vicinal position under PdI2/KI-catalyzed oxidative carbonylation conditions and found that also these substrates underwent carbonylative double cyclization to give previously unknown 1H-furo [3,4- [3,2-d]pyran-1,6-dione (Scheme 24c), and 6,7-dihydro-4H,9H-pyrano [4,3-b]thieno [2,3-d]pyran-4,9-dione (Scheme 24d) derivatives [76]. The process begins with 6-endo-dig cyclization from the carboxylic group followed by cyclocarbonylation, as exemplified in Scheme 24a to synthesize 1H-furo [3,4-b]thieno [3,2-d]pyran-1,5(3H)-diones from 3-(3-hydroxyprop-1-yn-1-yl)thiophene-2-carboxylic acids [76].…”

“…More recently, we studied the reactivity of thiophenecarboxylic acids having an ωhydroxyalkynyl substituent in vicinal position under PdI2/KI-catalyzed oxidative carbonylation conditions and found that also these substrates underwent carbonylative double cyclization to give previously unknown 1H-furo [3,4- [3,2-d]pyran-1,6-dione (Scheme 24c), and 6,7-dihydro-4H,9H-pyrano [4,3-b]thieno [2,3-d]pyran-4,9-dione (Scheme 24d) derivatives [76]. The process begins with 6-endo-dig cyclization from the carboxylic group followed by cyclocarbonylation, as exemplified in Scheme 24a to synthesize 1H-furo [3,4-b]thieno [3,2-d]pyran-1,5(3H)-diones from 3-(3-hydroxyprop-1-yn-1-yl)thiophene-2-carboxylic acids [76]. More recently, we studied the reactivity of thiophenecarboxylic acids having an ωhydroxyalkynyl substituent in vicinal position under PdI 2 /KI-catalyzed oxidative carbonylation conditions and found that also these substrates underwent carbonylative double cyclization to give previously unknown 1H-furo [3,4- [3,2-d]pyran-1,6-dione (Scheme 24c), and 6,7-dihydro-4H,9Hpyrano [4,3-b]thieno [2,3-d]pyran-4,9-dione (Scheme 24d) derivatives [76].…”

“…Scheme 24. Synthesis of (a) 1H-furo[3,4-b]thieno[3,2-d]pyran-1,5(3H)-diones, (b) 4H-furo[3,4b]thieno[2,3-d]pyran-4,8(6H)-diones, (c) 3,4-dihydro-1H,6H-pyrano[4,3-b]thieno[3,2-d]pyran-1,6-diones, and (d) 6,7-dihydro-4H,9H-pyrano[4,3-b]thieno[2,3-d]pyran-4,9-diones by PdI2/KI-catalyzed carbonylative double cyclization of thiophenecarboxylic acids bearing an ω-hydroxyalkynyl substituent in vicinal position[76].…”