Palladium-catalyzed highly regioselective mono and double Sonogashira cross-coupling reactions of 5-substituted-1,2,3-triiodobenzene under ambient conditions.

Raed M Al-Zoubi,Mothana K Al-Omari,Walid K Al-Jammal,Michael J Ferguson

doi:10.1039/d0ra01569e

Abstract

An efficient synthesis of 2,3-diiodinated diphenylacetylene and iodinated meta-terphenylacetylene derivatives through highly regioselective mono and double Sonogashira cross-coupling reactions of 5-substituted-1,2,3-triiodobenzene is reported. Significantly, the regioselectivity of coupling reactions is exclusively performed at the terminal C–I bonds, the less sterically hindered and the most regioactive positions. The highest isolated yields were achieved from reactions of electron-poor/neutral 1,2,3-triiodoarene and electron-rich arylacetylene derivatives. The use of 2.0 equiv. of arylacetylenes in one-pot fashion afforded the iodinated meta-terphenylacetylenes in excellent site selectivity and in good isolated yields. Different functional groups were found to be suitable under optimized conditions. This report discloses the first method to synthesize hitherto unknown 2,3-diiodinated diphenylacetylenes and iodinated meta-terphenylacetylenes that is facile, highly regioselective, general in scope and produces remarkable building blocks for other chemical transformations.

Highlights

Harnessing the regioselectivity to quickly access highly functionalized molecules by means of site-selective functional group transformation from adaptable building blocks is essential in synthetic chemistry and biology
A broad functional groups were examined under the optimized reaction conditions and found tolerant providing the desired terminal coupling products in highly regioselective manner that are difficult to make by alternative means
Langer and coworkers published the synthesis of quinolino[30,40:4,5]pyrrolo [1,2-f]phenanthridines via regioselective Sonogashira of 4chloro-3-iodo-2-methylquinoline with different aryl acetylenes in excellent regioselectivity towards the iodo substituent in moderate to good yields.[23]

Summary

Introduction

Harnessing the regioselectivity to quickly access highly functionalized molecules by means of site-selective functional group transformation from adaptable building blocks is essential in synthetic chemistry and biology. We report the rst synthetic method to access hitherto unknown 2,3-diiodinated diphenylacetylene derivatives by regioselective Sonogashira cross-coupling of 5-substituted-1,2,3-triiodobenzene that is efficient, scalable and affords moderate to good yields. A broad functional groups were examined under the optimized reaction conditions and found tolerant providing the desired terminal coupling products in highly regioselective manner that are difficult to make by alternative means.

Results

Conclusion