Toward a Template for Synthetic Actin-Targeting Macrolide Analogues That Inhibit Cancer Cell Invasiveness.

Actin barbed end-binding macrolides have been shown to inhibit cancer cell motility and invasion of extracellular matrix (ECM), evoking their potential utility as therapies for metastatic cancers. Unfortunately, the direct use of these compounds in clinical settings is impeded by their limited natural abundance, challenging total synthesis, and detrimental effects on normal tissues. To develop potent analogues of these compounds that are simpler to synthesize and compatible with cell-specific targeting systems, such as antibodies, we designed over 20 analogues of the acyclic side chain (tail) of the macrolide Mycalolide B. These analogues probed the contributions of four distinct regions of the tail towards the inhibition of actin polymerization and ECM invasion by human lung cancer A549 cells. We observed that two of these regions tolerate considerable substituent variability, and we identified a specific combination of substituents that leads to the optimal inhibition of the ECM invasion activity of A549 cells.

Transition metal-catalysis in interrupted borrowing hydrogen strategy.

In recent times, the transition metal-catalyzed borrowing hydrogen (BH) and interrupted borrowing hydrogen (IBH) strategies have attracted much attention and represent atom- and step-economic processes to access diverse building blocks via various C-C and C-heteroatom bond-forming reactions. The advantages of these approaches include (i) use of feedstock chemicals, (ii) high atom economy, (iii) no pre-activation of the substrates, and (iv) producing water as the only by-product. In this context, several synthetic strategies have been developed in this regime for the past few decades. To the best of our knowledge, no review article describes the important concepts of interrupted borrowing hydrogen (IBH) reaction. This review article highlights the recent advances in the IBH strategy and its application in sustainable chemical synthesis, particularly C-C bond formation using methanol as a C1 source, synthesis of 3,3'-bisindolylmethanes (3,3'-BIMs), α-branched ketones/diketones, and regioselective alkylation of N-heterocycles.

First-Row Transition-Metal Catalyzed Acceptorless Dehydrogenation and Related Reactions: A Personal Account.

The development of sustainable catalytic protocols that circumvent the use of expensive and precious metal catalysts and avoid toxic reagents plays a crucial role in organic synthesis. Indeed, the direct employment of simple and abundantly available feedstock chemicals as the starting materials broadens their synthetic application in contemporary research. In particular, the transition metal-catalyzed diversification of alcohols with various nucleophilic partners to construct a wide range of building blocks is a powerful and highly desirable methodology. Moreover, the replacement of precious metal catalysts by non-precious and less toxic metals for selective transformations is one of the main goals and has been paid significant attention to in modern chemistry. In view of this, the first-row transition metal catalysts find extensive applications in various synthetic transformations such as catalytic hydrogenation, dehydrogenation, and related reactions. Herein, we have disclosed our recent developments on the base-metal catalysis such as Mn, Fe, Co, and Ni for the acceptorless dehydrogenation reactions and its application in the C-C and C-N bond formation via hydrogen auto-transfer (HA) and acceptorless dehydrogenation coupling (ADC) reactions. These HA/ADC protocols employ alcohol as alkylating agents and eliminate water and/or hydrogen gas as by-products, representing highly atom-efficient and environmentally benign reactions. Furthermore, diverse simple to complex organic molecules synthesis by C-C and C-N bond formation using feedstock alcohols are also overviewed. Overall, this account deals with the contribution and development of efficient and novel homogeneous as well as heterogeneous base-metal catalysts for sustainable chemical synthesis.

Tandem Acceptorless Dehydrogenative Coupling-Decyanation under Nickel Catalysis.

The development of new catalytic processes based on abundantly available starting materials by cheap metals is always a fascinating task and marks an important transition in the chemical industry. Herein, a nickel-catalyzed acceptorless dehydrogenative coupling of alcohols with nitriles followed by decyanation of nitriles to access diversely substituted olefins is reported. This unprecedented C═C bond-forming methodology takes place in a tandem manner with the formation of formamide as a sole byproduct. The significant advantages of this strategy are the low-cost nickel catalyst, good functional group compatibility (ether, thioether, halo, cyano, ester, amino, N/O/S heterocycles; 43 examples), synthetic convenience, and high reaction selectivity and efficiency.

Recent advances in nickel-catalyzed C-C and C-N bond formation via HA and ADC reactions.

In recent times, earth-abundant 3d-transition-metal catalysts have attracted much attention in contemporary catalysis. They have been widely employed as suitable alternatives to their counterparts noble metals. In particular, nickel catalysts provide distinctive redox properties; thus, their efficiency in sustainable organic transformations is manifold. In this review article, recent advances in nickel-catalyzed hydrogen auto-transfer (HA) and acceptorless dehydrogenative coupling (ADC) reactions for the construction of C-C and C-N bonds have been discussed.

Nickel-Catalyzed Guerbet Type Reaction: C-Alkylation of Secondary Alcohols via Double (de)Hydrogenation.

Acceptorless double dehydrogenative cross-coupling of secondary and primary alcohols under nickel catalysis is reported. This Guerbet type reaction provides an atom- and a step-economical method for the C-alkylation of secondary alcohols under mild, benign conditions. A broad range of substrates including aromatic, cyclic, acyclic, and aliphatic alcohols was well tolerated. Interestingly, the C-alkylation of cholesterol derivatives and the double C-alkylation of cyclopentanol with various alcohols were also demonstrated.

Selective hydrogenation of primary amides and cyclic di-peptides under Ru-catalysis.

A ruthenium(ii)-catalyzed selective hydrogenation of challenging primary amides and cyclic di-peptides to their corresponding primary alcohols and amino alcohols, respectively, is reported. The hydrogenation reaction operates under mild and eco-benign conditions and can be scaled-up.

Catalytic conversion of ketones to esters via C(O)-C bond cleavage under transition-metal free conditions.

The catalytic conversion of ketones to esters via C(O)-C bond cleavage under transition-metal free conditions is reported. This catalytic process proceeds under solvent-free conditions and offers an easy operational procedure, broad substrate scope with excellent selectivity, and reaction scalability.

Iron-Catalyzed Direct Julia-Type Olefination of Alcohols.

Herein, we report an iron-catalyzed, convenient, and expedient strategy for the synthesis of styrene and naphthalene derivatives with the liberation of dihydrogen. The use of a catalyst derived from an earth-abundant metal provides a sustainable strategy to olefins. This method exhibits wide substrate scope (primary and secondary alcohols) functional group tolerance (amino, nitro, halo, alkoxy, thiomethoxy, and S- and N-heterocyclic compounds) that can be scaled up. The unprecedented synthesis of 1-methyl naphthalenes proceeds via tandem methenylation/double dehydrogenation. Mechanistic study shows that the cleavage of the C-H bond of alcohol is the rate-determining step.

Manganese(I)-Catalyzed Sustainable Synthesis of Quinoxaline and Quinazoline Derivatives with the Liberation of Dihydrogen.

Direct synthesis of N-heterocycles via the acceptorless dehydrogenative coupling is very challenging and scarcely reported under 3d transition-metal catalysis. Here, we have developed an efficient Mn(I)-catalyzed sustainable synthesis of various quinoxalines from 1,2-diaminobenzenes and 1,2-diols via the acceptorless dehydrogenative coupling reaction. Further, this strategy was successfully applied for the unprecedented synthesis of quinazolines by the reaction of 2-aminobenzyl alcohol with primary amides. The present protocol provides an atom-economical and sustainable route for the synthesis of various quinoxaline and quinazoline derivatives by employing an earth-abundant manganese salt and simple phosphine-free NNN-tridentate ligand.

General Synthesis of N-Alkylation of Amines with Secondary Alcohols via Hydrogen Autotransfer.

Direct catalytic N-alkylation of amines with secondary alcohols via hydrogen autotransfer (HA) strategy is very challenging and has been scarcely reported, even under precious metal catalysis. Herein, an efficient N-alkylation of amines, including benzylamines using secondary alcohols as alkylating agents, is reported. This reaction is catalyzed by a molecularly defined NNN-Ni(II) pincer complex, and the reaction operates under mild, benign conditions. Various substrates and functional groups were tolerated. Preliminary mechanistic studies suggest that the N-alkylation reaction proceeds via a hydrogen autotransfer mechanism.

Nickel-Catalyzed Chemoselective Acetalization of Aldehydes With Alcohols under Neutral Conditions.

A molecularly defined NiII -complex catalyzing the chemoselective acetalization of aldehydes with alcohols under neutral conditions is reported. The reaction is general, efficient and showed a wide substrate scope (including aliphatic aldehydes) as well as excellent functional group tolerance. Reusability of the present nickel catalyst is also demonstrated.

Nickel(ii)-catalyzed direct olefination of benzyl alcohols with sulfones with the liberation of H2.

A nickel(ii)-catalyzed direct olefination of benzyl alcohols with sulfones to access various terminal and internal olefins with the liberation of hydrogen gas is reported.

Manganese-Catalyzed Direct Conversion of Ester to Amide with Liberation of H2.

A simple and efficient Mn-catalyzed acylation of amines is achieved using both acyl and alkoxy functions of unactivated esters with the liberation of molecular hydrogen as a sole byproduct. The present protocol provides an atom-economical and sustainable route for the synthesis of amides from esters by employing an earth-abundant manganese salt and inexpensive phosphine-free tridentate ligand.

Nickel-catalyzed N-vinylation of heteroaromatic amines via C-H bond activation.

Here, we report a ligand- and reductant-free nickel-catalyzed N-vinylation of heteroaromatic amines using biorenewable p-cymene as a solvent. This unprecedented cross-coupling strategy has high functional group tolerance (halides, alkoxy, cyano, chiral motif, etc.) and proceeded via C-H bond activation.