Regioselective 5‐endo‐dig Electrophilic Iodocyclization of Enediynes: A Convenient Route to Iodo‐substituted Indenes and Cyclopenta‐Fused Arenes

Abstract

An efficient iodine-mediated regioselective tandem approach for the synthesis of symmetric and asymmetric iodo-substituted indenes and stereoselective cyclopenta [b]pyridine/thiophenes from easily accessible enediynes that proceeds by in situ formation of an iodonium intermediate followed by a regioselective 5-endo-dig cyclization has been described. The intramolecular electrophilic iodocyclization was selectively triggered by a distribution of electronic density along the alkyne bond. Subsequently, the iodo-substituted indenes were diversified by employing palladium-catalyzed cross-coupling reactions and the coupled products were further confirmed by X-ray crystallographic studies.

1-Iodobuta-1,3-diynes in Copper-Catalyzed Azide–Alkyne Cycloaddition: A One-Step Route to 4-Ethynyl-5-iodo-1,2,3-triazoles

“…It is important that both types of products, triazole-fused enediynes and 5-aryl-4-ethynyltriazoles, are of special importance because of possible further intramolecular cyclizations known for other types of benzene­(heteroarene)-fused enediynes − and ortho -ethynylaryl-substituted arenes, − leading to highly conjugated polyaromatic compounds. Among such systems, polycyclic fused 1,2,3-triazoles are of particular interest. − …”

Relative Reactivity of Benzothiophene-Fused Enediynes in the Bergman Cyclization

“…Nowadays enediynes are still of great interest for the discovery of novel anticancer agents − and in other fields, i.e., for the synthesis of polymers − and polyaromatic compounds using transition metal catalysts and other reaction mechanisms. − By today, numerous derivatives with a ( Z )-hexa-3-en-1,5-diyne scaffold have been synthesized and explored. There are several detailed recent reviews devoted to the synthesis of naturally occurring enediynes and their analogues, ,− 9-membered and other highly strained enediynes, complexes of enediynes with metals …”

Borylative cyclisation of diynes using BCl3 and borocations

“…The use of "better" halide donors (i.e. free halide as in previously reported systems using HBr or I 2 ) 11,12 is not possible in this system as these would react with BCl 3 (to form [X-BCl 3 ] − , X = halide). Furthermore, the use of weaker Lewis acids e.g.…”

“…1), has been previously reported from the addition of HBr to ortho-bis( phenylethynyl)benzene, with alkyne protonation initiating the 5-endo-dig cyclisation. 11 In contrast to the use of HBr (or I 2 ), 12 using BCl 3 as the electrophile incorporates a nucleophilic C-B site in addition to an electrophilic C-X. The formation of 2-BCl 2 presumably arises from a zwitterionic vinyl cation intermediate (Scheme 1, top middle) being trapped by chloride instead of undergoing intramolecular S E Ar.…”