ABSTRACT
Alpha-arylated carbonyl compounds are commonly occurring motifs in biologically interesting molecules and are therefore of high interest to the pharmaceutical industry. Conventional procedures for their synthesis often result in complications in scale-up, such as the use of stoichiometric amounts of toxic reagents and harsh reaction conditions. Over the last decade, significant efforts have been directed towards the development of metal-catalyzed alpha-arylations of carbonyl compounds as an alternative synthetic approach that operates under milder conditions. This Review summarizes the developments in this area to date, with a focus on how the substrate scope has been expanded through selection of the most appropriate synthetic method, such as the careful choice of ligands, precatalysts, bases, and reaction conditions.
Subject(s)
Metals/chemistry , Aldehydes/chemistry , Amides/chemistry , Carbon/chemistry , Catalysis , Ketones/chemistry , Nitriles/chemistry , Palladium/chemistryABSTRACT
We report a new Pd(II)-catalyzed C-H bond amination reaction to form carbazoles, an important motif that is prevalent in a range of systems. The catalytic amination process operates under extremely mild conditions and produces carbazole products in good to excellent yields. Carbazoles possessing complex molecular architecture can also be formed using this reaction, highlighting its potential in natural product synthesis applications. Preliminary mechanistic investigations reveal the reaction proceeds through a Pd(II)/Pd(IV) manifold and that reductive elimination from a high oxidation state Pd(IV) complex facilitates the mild conditions of this transformation.
Subject(s)
Carbazoles/chemistry , Carbon/chemistry , Hydrogen/chemistry , Palladium/chemistry , Temperature , Amination , Catalysis , Glycosylation , Models, Molecular , Molecular Structure , Oxidation-ReductionABSTRACT
Enantioselective organocatalysis has emerged as a powerful synthetic paradigm that is complementary to metal-catalysed transformations and has accelerated the development of new methods to make diverse chiral molecules. The operational simplicity, ready availability of catalysts and low toxicity associated with organocatalysis makes it an attractive method to synthesise complex structures. Here, we discuss the impact of enamine, iminium, nucleophilic and Brønsted acid catalysts in organic synthesis, and highlight key strategic methods to assemble useful molecules with high enantiomeric purity.
