Aditya L. Gottumukkala

Palladium‐Catalyzed C3 or C4 Direct Arylation of Heteroaromatic Compounds with Aryl Halides by CH Bond Activation

In recent years, palladium‐catalyzed direct C2 or C5 arylation of heteroaromatic compounds with aryl halides by CH bond activation has become a popular method for generating carbon–carbon bonds. For this reaction, a wide variety of heteroaromatics, such as furans, thiophenes, pyrroles, thiazoles, oxazoles, imidazoles, pyrazoles, indoles, triazoles, or even pyridines, can be employed. C3 and C4 arylations of heteroaromatics by CH bond activation have also been described. Such reactions initially attracted much less attention than the C2 or C5 arylations due to the lower reactivity of the C3 and C4 positions. How‐ ever, in more recent years, several results from using modified and improved catalysts and reaction conditions have been reported, which permit C3 and C4 arylations in synthetically useful yields. Several intramolecular cyclizations of 2‐substituted heterocycles have been described, with formation of a CC bond on C3 resulting in the formation of five‐ to nine‐membered rings incorporating pyrroles, indoles, thiophenes, furans, isoxazoles, or pyridines. Intermolecular C3 or C4 direct arylations are still quite rare for some heteroaromatics and are in several cases not highly regioselective. For such reactions, the best results have been obtained using pyrroles, thiophenes, or furans. For selected substrates, regioselective arylation at C3 or C4 of the heteroaromatic compounds took place under appropriate reaction conditions. Only a few examples of intermolecular couplings using oxazoles, thiazoles, imidazoles, isoxazoles, pyrazoles, triazoles, or pyridines have been reported. For most of these reactions, aryl iodides or bromides have been used as coupling partners, although a few examples with aryl chlorides are also known. This method allows the synthesis of complex molecules in only a few steps, and will provide access to a very wide variety of new heteroaryl derivatives in the next years.

Pd-Diimine: A Highly Selective Catalyst System for the Base-Free Oxidative Heck Reaction

Pd(OAc)(2)/3 is an efficient catalyst system for the base-free oxidative Heck reaction that outperforms the currently available catalysts for the more challenging substrates studied. The catalyst system is highly selective, and works at room temperature with dioxygen as the oxidant.

Palladium-catalyzed asymmetric quaternary stereocenter formation

An efficient palladium catalyst is presented for the formation of benzylic quaternary stereocenters by conjugate addition of arylboronic acids to a variety of β,β-disubstituted carbocyclic, heterocyclic, and acyclic enones. The catalyst is readily prepared from PdCl(2), PhBOX, and AgSbF(6), and provides products in up to 99% enantiomeric excess, with good yields. Based on this strategy, (-)-α-cuparenone has been prepared in only two steps.

Aqueous Oxidative Heck Reaction as a Protein-Labeling Strategy

An increasing number of chemical reactions are being employed for bio‐orthogonal ligation of detection labels to protein‐bound functional groups. Several of these strategies, however, are limited in their application to pure proteins and are ineffective in complex biological samples such as cell lysates. Here we present the palladium‐catalyzed oxidative Heck reaction as a new and robust bio‐orthogonal strategy for linking functionalized arylboronic acids to protein‐bound alkenes in high yields and with excellent chemoselectivity even in the presence of complex protein mixtures from living cells. Advantageously, this reaction proceeds under aerobic conditions, whereas most other metal‐catalyzed reactions require inert atmosphere.

Z-Selectivity: A Novel Facet of Metathesis

Notwithstanding the significant progress made in olefination reactions, a key challenge in organic chemistry has been the development of efficient Z-selective olefination. The most common methods for olefin synthesis, namely Wittig, Horner– Wadsworth–Emmons (HWE) and their variants, or even olefin metathesis, rely on a [2+2] cycloaddition-retrocycloaddition sequence to afford the alkene (Scheme 1). However, the retro-cy-