Synthesis of Strained 1,3-Diene Macrocycles via Copper-Mediated Castro–Stephens Coupling/Alkyne Reduction Tandem Reactions

• Published in: Organic letters Vol. 17; no. 15; pp. 3902 - 3905
• Main Authors: Li, Wei, Schneider, Christopher M, Georg, Gunda I
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07-08-2015
• Subjects: Alkynes - chemistry; Catalysis; Combinatorial Chemistry Techniques; Copper - chemistry; Cyclization; Macrocyclic Compounds - chemical synthesis; Macrocyclic Compounds - chemistry; Molecular Structure
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.5b01892

A copper-mediated macrocyclization involving the reaction of a vinyl iodide and a terminal alkyne followed by an in situ reduction of the enyne intermediate is reported. The reaction generates a conjugated Z-double bond within a strained medium-size lactone, lactam, or ether macrocycle. A variety of macrocyclic compounds bearing different ring sizes and functionalities were synthesized. A complementary stepwise procedure was also developed for less strained ring systems.