There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Catalytic dehydrogenative cross-coupling: forming carbon-carbon bonds by oxidizing two carbon-hydrogen bonds

The site-selective formation of carbon-carbon bonds through direct functionalizations of otherwise unreactive carbon-hydrogen bonds constitutes an economically attractive strategy for an overall streamlining of sustainable syntheses. In recent decades, intensive research efforts have led to the development of various reaction conditions for challenging C-H bond functionalizations, among which transition-metal-catalyzed transformations arguably constitute thus far the most valuable tool. For instance, the use of inter alia palladium, ruthenium, rhodium, copper, or iron complexes set the stage for chemo-, site-, diastereo-, and/or enantioselective C-H bond functionalizations. Key to success was generally a detailed mechanistic understanding of the elementary C-H bond metalation step, which depending on the nature of the metal fragment can proceed via several distinct reaction pathways. Traditionally, three different modes of action were primarily considered for CH bond metalations, namely, (i) oxidative addition with electronrich late transition metals, (ii) σ-bond metathesis with early transition metals, and (iii) electrophilic activation with electrondeficient late transition metals (Scheme 1). However, more recent mechanistic studies indicated the existence of a continuum of electrophilic, ambiphilic, and nucleophilic interactions. Within this continuum, detailed experimental and computational analysis provided strong evidence for novel C-H bond metalationmechanisms relying on the assistance of a bifunctional ligand bearing an additional Lewis-basic heteroatom, such as that found in (heteroatom-substituted) secondary phosphine oxides or most prominently carboxylates (Scheme 1, iv). This novel insight into the nature of stoichiometric metalations has served as stimulus for the development of novel transformations based on cocatalytic amounts of carboxylates, which significantly broadened the scope of C-H bond functionalizations in recent years, with most remarkable progress being made in palladiumor ruthenium-catalyzed direct arylations and direct alkylations. These carboxylate-assisted C-H bond transformations were mostly proposed to proceed via a mechanism in which metalation takes place via a concerted base-assisted deprotonation. To mechanistically differentiate these intramolecular metalations new acronyms have recently been introduced into the literature, such as CMD (concerted metalationdeprotonation), IES (internal electrophilic substitution), or AMLA (ambiphilic metal ligand activation), which describe related mechanisms and will be used below where appropriate. This review summarizes the development and scope of carboxylates as cocatalysts in transition-metal-catalyzed C-H functionalizations until autumn 2010. Moreover, experimental and computational studies on stoichiometric metalation reactions being of relevance to the mechanism of these catalytic processes are discussed as well. Mechanistically related C-H bond cleavage reactions with ruthenium or iridium complexes bearing monodentate ligands are, however, only covered with respect to their working mode, and transformations with stoichiometric amounts of simple acetate bases are solely included when their mechanism was suggested to proceed by acetate-assisted metalation.

Carboxylate-assisted transition-metal-catalyzed C-H bond functionalizations: mechanism and scope.

3.7. Palladium Nanoparticles as Catalysts 888 3.8. Other Transition-Metal Complexes 888 3.9. Transition-Metal-Free Reactions 889 4. Applications 889 4.1. Alkynylation of Arenes 889 4.2. Alkynylation of Heterocycles 891 4.3. Synthesis of Enynes and Enediynes 894 4.4. Synthesis of Ynones 896 4.5. Synthesis of Carbocyclic Systems 897 4.6. Synthesis of Heterocyclic Systems 898 4.7. Synthesis of Natural Products 903 4.8. Synthesis of Electronic and Electrooptical Molecules 906

https://www.chem.ccu.edu.tw/~joyce/referance/ericyang/Chem.%20Rev/Chem.%20Rev.%202007,%20107,%20874-922.pdf

The Sonogashira Reaction: A Booming Methodology in Synthetic Organic Chemistry†

The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals

A novel synthesis of macrocyclic arylketones via Pd-catalyzed cross-coupling of arylboronic acids and carboxylic acids, either before or in situ activated by the treatment with disuccinimidyl carbonate, is disclosed.

Synthesis of Macrocyclic Ketones Exploiting Palladium-Catalyzed Activation of Carboxylic Acids as an Enabling Step.

Installation of cyano (CN-) functionality onto nucleosides has always been a challenging task for chemists and catalytic protocols developed for simple aryl substrates in most cases have failed to replicate their success when applied to nucleobase or sugar moiety of nucleosides. Given the importance of the cyano and amide functionalities in nucleoside chemistry, we herein disclose an efficient Pd-catalyzed cyanation protocol specifically applied to iodo-nucleobases. Furthermore, the developed methodology of cyanation has been explored for synthesis of naturally occurring and bio-active nucleosides such as toyocamycin, sangivamycin and Mycalisine A precursor has been demonstrated.

Palladium-Catalyzed Cyanation of Nucleobases: Total Synthesis of Toyocamycin, Sangivamycin, and a Mycalisine A Precursor

A new palladium(II) precatalyst for Suzuki cross-coupling of aryl halides and organoboronic acids has been identified, namely bis(triphenylphosphine)palladium(II)succinimide [(Ph3P)2Pd(N-Succ)2] 2 . The precatalyst is easily prepared from palladium(0) precursors, such as (Ph3P)4Pd or Pd2dba3·CHCl3/Ph3P and succinimide, is air, light and moisture stable, and may be employed with a variety of substrates to give the cross-coupled products, in good yields and in reasonable time, at relatively low catalyst loadings.

Bis(triphenylphosphine)palladium(II)succinimide as a Precatalyst for Suzuki Cross‐Coupling — Subtle Effects Exerted by the Succinimide Ligand.

Nucleosides modification via conventional cross-coupling has been performed using different catalytic systems and found to take place via long reaction times. However, since the pandemic, nucleoside-based antivirals and vaccines have received widespread attention and the requirement for rapid modification and synthesis of these moieties has become a major objective for researchers. To address this challenge, we describe the development of a rapid flow-based cross-coupling synthesis protocol for a variety of C5-pyrimidine substituted nucleosides. The protocol allows for facile access to multiple nucleoside analogues in very good yields in a few minutes compared to conventional batch chemistry. To highlight the utility of our approach, the synthesis of an anti-HSV drug, BVDU was also achieved in an efficient manner using our new protocol.The online version contains supplementary material available at 10.1007/s41981-023-00265-1. 

/pdf/rapid-plugged-flow-synthesis-of-nucleoside-analogues-via-tqxsxho5.pdf

Rapid plugged flow synthesis of nucleoside analogues via Suzuki-Miyaura coupling and heck Alkenylation of 5-Iodo-2’-deoxyuridine (or cytidine)

The novel pincer-type NHC-precursor (IPB) is efficiently used for arylation of anthracenes with aryl boronic acids.

Anant R. Kapdi

Papers

Synthesis of Macrocyclic Ketones Exploiting Palladium-Catalyzed Activation of Carboxylic Acids as an Enabling Step.

Palladium-Catalyzed Cyanation of Nucleobases: Total Synthesis of Toyocamycin, Sangivamycin, and a Mycalisine A Precursor

Bis(triphenylphosphine)palladium(II)succinimide as a Precatalyst for Suzuki Cross‐Coupling — Subtle Effects Exerted by the Succinimide Ligand.

Rapid plugged flow synthesis of nucleoside analogues via Suzuki-Miyaura coupling and heck Alkenylation of 5-Iodo-2’-deoxyuridine (or cytidine)

Pincer CNC Bis‐N‐heterocyclic Carbenes: Robust Ligands for Palladium‐Catalyzed Suzuki—Miyaura Arylation of Bromoanthracene and Related Substrates.