Sonogashira coupling in natural product synthesis

Abstract

This review will focus on selected applications of Sonogashira coupling and subsequent transformations as key steps in the total synthesis of natural products.

Enantioselective Desymmetrization of Cyclobutanones Enabled by Synergistic Palladium/Enamine Catalysis

“…Strained cyclobutanes, especially aryl‐substituted cyclobutanes, are present in many natural products and bioactive molecules (Figure ) . The enantioselective synthesis of chiral cyclobutanes is an ongoing challenge in synthetic chemistry . A number of methods have been developed to access enantiomerically enriched cyclobutane scaffolds, including [2+2] cycloaddition, rearrangement, and other transformations .…”

A Sustainable, User‐Friendly Protocol for the Pd‐Free Sonogashira Coupling Reaction

“…In natural product synthesis, the Sonogashira reaction can be used as the key coupling step to synthesize conjugated enynes or enediynes. It can be also combined with transformations that convert the triple bond into other functionalities, or with regioselective hetero‐annulation, leading to heterocyclic products . Aryl‐alkyne and conjugated alkenyne moieties are moreover contained in many intermediates or precursors used in the synthesis of non‐linear optical materials and polymers utilized in applications such as molecular electronics…”

Direct C‐H Arylation of N‐Heterocycles with Aryl Triazenes Using Molecular Oxygen as Oxidant

“…[6] Many of these reactions also suffer from harsh conditions and poor functional group tolerance. Recently, a number of interesting reports have appeared for direct CÀ H arylation of such N-heterocycles, [7][8][9][10][11][12][13][14][15][16] but the direct CÀ H arylation of electron deficient N-heterocycles is still exigent and fascinating. Lei et al have achieved the direct CÀ H arylation of isoquinolines in the presence of 4 equivalents of aryl diazonium salts using 40 W white LED and ruthenium photo-catalyst under inert conditions.…”

“…to arylate the pyridine core primarily, with just two examples of isoquinoline. [16] Vishwakarma et al employed boronic acids to realize the arylation of such N-heterocycles using Fe(acac) 2 /K 2 S 2 O 8 combination. [15] Considering the previous key approaches for direct CÀ H arylation (Scheme 1), there exists enough scope and potential to develop a convenient approach for the arylation of such heteroarenes.…”

“…Based on the above control experiment and existing literature, 13,16 a plausible mechanism is outlined in Scheme 3.…”