Ruthenium-Catalyzed Self-Coupling of Secondary Alcohols.

A simple catalytic method for self-coupling of secondary alcohols leading to the synthesis of ß-branched ketones under mild conditions is reported. Well-defined ruthenium pincer complex catalyzed the reactions. Optimization studies revealed that sodium tert-butoxide is an appropriate base for this transformation. Functionalized aryl methanols, heteroaryl methanols, and linear and branched aliphatic secondary alcohols underwent facile catalytic self-coupling reactions. Mechanistic studies revealed that both catalyst and base are crucial to achieve dehydrogenation of secondary alcohols to ketones, their subsequent controlled aldol condensation, and further hydrogenation of α,ß-unsaturated intermediates, leading to the selective formation of ß-branched ketone products. Notably, the noninnocent PNP ligand which displays amine-amide metal-ligand cooperation operative in a catalyst played a key role in facilitating this catalytic self-coupling of secondary alcohols. Liberated molecular hydrogen and water are the only byproducts.

Direct Synthesis of Aldoximes: Ruthenium-Catalyzed Coupling of Alcohols and Hydroxylamine Hydrochloride.

A catalytic method for the direct synthesis of oximes from alcohols and hydroxyl amine hydrochloride salt is reported. The reaction is catalyzed by a ruthenium pincer catalyst, which oxidizes alcohols involving amine-amide metal-ligand cooperation, and the in situ formed aldehydes condense with hydroxyl amine to deliver the oximes. Notably, the reaction requires only a catalyst and base; water and liberated hydrogen are the only byproducts, making this protocol attractive and environmentally benign.

Ruthenium-Catalyzed Selective α-Alkylation of ß-Naphthols using Primary Alcohols: Elucidating the Influence of Base and Water.

Functionalized arenes and arenols have diverse applications in chemical synthesis and material chemistry. Selective functionalization of arenols is a topic of prime interest. In particular, direct alkylation of arenols using alcohols is a challenging task. In this report, a ruthenium pincer catalyzed direct α-alkylation of ß-naphthol using primary alcohols as alkylating reagents is reported. Notably, aryl and heteroaryl methanols and linear and branched aliphatic alcohols underwent selective alkylation reactions, in which water is the only byproduct. Notably, catalytically derived α-alkyl-ß-naphthol products displayed high absorbance, emissive properties, and quantum yields (up to 93.2 %). Dearomative bromination on α-alkyl-ß-naphthol is demonstrated as a synthetic application. Mechanistic studies indicate that the reaction involves an aldehyde intermediate. DFT studies support this finding and further reveal that a stoichiometric amount of base is required to make the aldol condensation as well as elementary steps required for regeneration of catalytically active species. In situ-generated water molecule from the aldol condensation reaction plays an important role in the regeneration of an active catalyst.

Cobalt-catalysed [1,2]-Wittig rearrangement of ethers to secondary alcohols.

Stable ethers are successfully transformed into secondary alcohols via C-O bond activation using a simple cobalt pincer catalyst. Mechanistic studies indicate the involvement of radical pairs, and their sequential recombination and the subsequent hydrolysis results in the formation of secondary alcohols.

Ruthenium-catalysed α-prenylation of ketones using prenol.

Prenol and isoprenoids are common structural motifs in biological systems and possess diverse applications. An unprecedented direct catalytic prenylation of ketones using prenol is attained. This C-C bond formation reaction requires only a ruthenium pincer catalyst and a base, and H2O is the only byproduct.

A Boron-Nitrogen Double Transborylation Strategy for Borane-Catalyzed Hydroboration of Nitriles.

Organoborane-catalyzed hydroboration of nitriles provides N,N-diborylamines, which act as efficient synthons for the synthesis of primary amines and secondary amides. Known nitrile hydroboration methods are dominated by metal catalysis. Simple and metal-free hydroboration of nitriles using diborane [H-B-9-BBN]2 as a catalyst and pinacolborane as a turnover reagent is reported. The reaction of monomeric H-B-9-BBN with nitriles leads to the hydrido-bridged diborylimine intermediate; a subsequent sequential double hydroboration-transborylation pathway involving B-N/B-H σ bond metathesis is proposed.

Base-Catalyzed Traceless Silylation and Deoxygenative Cyclization of Chalcones to Cyclopropanes.

Development of simple synthetic methods from readily available compounds to complex products is of utmost interest in modern synthesis. Catalytic synthesis of cyclopropanes is important for diverse chemical applications. We present a method for the transformation of readily accessible α,ß-unsaturated ketones (chalcones) to cyclopropanes. A simple base, KOH, catalyzed the selective reduction of the enone carbonyl functionality, dehydrogenative silylation, and deoxygenative cyclization of chalcones to provide the cyclopropane products. Chalcones with extended conjugation and 4-chromanone-based substrates also provided the corresponding cyclopropanes. One-pot synthesis of cyclopropanes directly from industrial feedstock compounds such as ketones and aldehydes is also demonstrated using catalytic KOH for both intermolecular condensation and dehydrogenative silylation-deoxygenative intramolecular cyclization cascade.

Catalytic Hydrogenation of Epoxides to Alcohols.

Atom-economical catalytic reactions are a highly enticing strategy because all atoms of the starting materials are incorporated into the products. Catalytic hydrogenation of epoxides to alcohols is an attractive and alternative protocol to other synthetic methodologies for the synthesis of alcohols from alkenes. In the last two decades, catalytic hydrogenation of epoxides to alcohols has made remarkable progress in chemical synthesis. In this review, an overview of the catalytic hydrogenation of both terminal and internal epoxides to the corresponding alcohols is presented. An outline of both homogeneous and heterogeneous hydrogenation of epoxides to the corresponding alcohols is provided. Moreover, the selectivity, efficiency, and the reaction mechanisms of these epoxide hydrogenation reactions are highlighted.

Manganese(I) Catalyzed Alkenylation of Phosphine Oxides Using Alcohols with Liberation of Hydrogen and Water.

Herein, a catalytic cross-coupling of methyldiphenylphosphine oxide with arylmethyl alcohols leading to the alkenylphosphine oxides is reported. A manganese pincer catalyst catalyzes the reactions, which provides exclusive formation of trans-alkenylphosphine oxides. Mechanistic studies indicate that reactions proceed via aldehyde intermediacy and the catalyst promotes the C═C bond formation. Reactions are facilitated by dearomatization, and aromatization metal-ligand cooperation operates in catalyst. Use of abundant base metal catalyst and formation of water and H2 as the only byproducts make this catalytic protocol sustainable and environmentally benign.

Ruthenium(ii)-catalysed 1,2-selective hydroboration of aldazines.

Herein, an efficient and simple catalytic method for the selective and partial reduction of aldazines using ruthenium catalyst [Ru(p-cymene)Cl2]2 (1) has been accomplished. Under mild conditions, aldazines undergo the addition of pinacolborane in the presence of a ruthenium catalyst, which delivered N-boryl-N-benzyl hydrazone products. Notably, the reaction is highly selective, and results in exclusive mono-hydroboration and desymmetrization of symmetrical aldazines. Mechanistic studies indicate the involvement of in situ formed intermediate [{(η6-p-cymene)RuCl}2(µ-H-µ-Cl)] (1a) in this selective hydroboration.

Manganese(I) Catalyzed α-Alkenylation of Amides Using Alcohols with Liberation of Hydrogen and Water.

Herein, unprecedented manganese-catalyzed direct α-alkenylation of amides using alcohols is reported. Aryl amides are reacted with diverse primary alcohols, which provided the α,ß-unsaturated amides in moderate to good yields with excellent selectivity. Mechanistic studies indicate that Mn(I) catalyst oxidizes the alcohols to their corresponding aldehydes and also plays an important role in efficient C═C bond formation through aldol condensation. This selective olefination is facilitated by metal-ligand cooperation by the aromatization-dearomatization process operating in the catalytic system. Biorenewable alcohols are used as alkenylation reagents for the challenging α-alkenylation of amides with the highly abundant base metal manganese as a catalyst, which results in water and dihydrogen as the only byproduct, making this catalytic transformation attractive, sustainable, and environmentally benign.

Ruthenium-Catalyzed α-Alkylation of Ketones Using Secondary Alcohols to ß-Disubstituted Ketones.

An assortment of aromatic ketones was successfully functionalized with a variety of unactivated secondary alcohols that serve as alkylating agents, providing ß-disubstituted ketone products in good to excellent yields. Remarkably, challenging substrates such as simple acetophenone derivatives are effectively alkylated under this ruthenium catalysis. The substituted cyclohexanol compounds displayed product-induced diastereoselectivity. Mechanistic studies indicate the involvement of the hydrogen-borrowing pathway in these alkylation reactions. Notably, this selective and catalytic C-C bond-forming reaction requires only a minimal load of catalyst and base and produces H2O as the only byproduct, making this protocol attractive and environmentally benign.

Direct Catalytic Symmetrical, Unsymmetrical N,N-Dialkylation and Cyclization of Acylhydrazides Using Alcohols.

Herein, direct N,N-dialkylation of acylhydrazides using alcohols is reported. This catalytic protocol provides one-pot synthesis of both symmetrical and unsymmetrical N,N-disubstituted acylhydrazides using an assortment of primary and secondary alcohols with remarkable selectivity and excellent yields. Interestingly, the use of diols resulted in intermolecular cyclization of acylhydrazides, and such products are privileged structures in biologically active compounds. Water is the only byproduct, which makes this catalytic protocol sustainable and environmentally benign.

Cobalt-catalysed selective synthesis of aldehydes and alcohols from esters.

Efficient and selective reduction of esters to aldehydes and alcohols is reported in which a simple cobalt pincer catalyst catalyses both transformations using diethylsilane as a reductant. Remarkably, the reaction selectivity is controlled by the stoichiometry of diethylsilane.

Cobalt-Catalyzed Acceptorless Dehydrogenation of Alcohols to Carboxylate Salts and Hydrogen.

The facile oxidation of alcohols to carboxylate salts and H2 is achieved using a simple and readily accessible cobalt pincer catalyst (NNNHtBuCoBr2). The reaction follows an acceptorless dehydrogenation pathway and displays good functional group tolerance. The amine-amide metal-ligand cooperation in cobalt catalyst is suggested to facilitate this transformation. The mechanistic studies indicate that in-situ-formed aldehydes react with a base through a Cannizzaro-type pathway, resulting in potassium hemiacetolate, which further undergoes catalytic dehydrogenation to provide the carboxylate salts and H2.

KOtBu-Catalyzed Michael Addition Reactions Under Mild and Solvent-Free Conditions.

Designed transition metal complexes predominantly catalyze Michael addition reactions. Inorganic and organic base-catalyzed Michael addition reactions have been reported. However, known base-catalyzed reactions suffer from the requirement of solvents, additives, high pressure and also side-reactions. Herein, we demonstrate a mild and environmentally friendly strategy of readily available KOt Bu-catalyzed Michael addition reactions. This simple inorganic base efficiently catalyzes the Michael addition of underexplored acrylonitriles, esters and amides with (oxa-, aza-, and thia-) heteroatom nucleophiles. This catalytic process proceeds under solvent-free conditions and at room temperature. Notably, this protocol offers an easy operational procedure, broad substrate scope with excellent selectivity, reaction scalability and excellent TON (>9900). Preliminary mechanistic studies revealed that the reaction follows an ionic mechanism. Formal synthesis of promazine is demonstrated using this catalytic protocol.

Ruthenium-Catalyzed Selective Hydrogenation of Epoxides to Secondary Alcohols.

A ruthenium(II)-catalyzed highly selective Markovnikov hydrogenation of terminal epoxides to secondary alcohols is reported. Diverse substitutions on the aryl ring of styrene oxides are tolerated. Benzylic, glycidyl, and aliphatic epoxides as well as diepoxides also underwent facile hydrogenation to provide secondary alcohols with exclusive selectivity. Metal-ligand cooperation-mediated ruthenium trans-dihydride formation and its reaction involving oxygen and the less substituted terminal carbon of the epoxide is envisaged for the origin of the observed selectivity.

Manganese(I)-Catalyzed Cross-Coupling of Ketones and Secondary Alcohols with Primary Alcohols.

Catalytic cross-coupling of ketones and secondary alcohols with primary alcohols is reported. An abundant manganese-based pincer catalyst catalyzes the reactions. Low loading of catalyst (2 mol %) and catalytic use of a mild base (5-10 mol %) are sufficient for efficient cross-coupling. Various aryl and heteroaryl ketones are catalytically cross-coupled with primary alcohols to provide the selective α-alkylated products. Challenging α-ethylation of ketones is also attained using ethanol as an alkylating reagent. Further, direct use of secondary alcohols in the reaction results in in situ oxidation to provide the ketone intermediates, which undergo selective α-alkylation. The reaction proceeds via the borrowing hydrogen pathway. The catalyst oxidizes the primary alcohols to aldehydes, which undergo subsequent aldol condensation with ketones, promoted by catalytic amount of Cs2CO3, to provide the α,ß-unsaturated ketone intermediates. The hydrogen liberated from oxidation of alcohols is used for hydrogenation of α,ß-unsaturated ketone intermediates. Notably either water or water and dihydrogen are the only byproducts in these environmentally benign catalytic processes. Mechanistic studies allowed inferring all of the intermediates involved. Dearomatization-aromatization metal-ligand cooperation in the catalyst facilitates the facile O-H bond activation of both primary and secondary alcohols, and the resultant manganese alkoxide complexes produce corresponding carbonyl compounds, perhaps via ß-hydride elimination. The manganese(I) hydride intermediate plays dual role as it hydrogenates α,ß-unsaturated ketones and liberates molecular hydrogen to regenerate the catalytically active dearomatized intermediate. Metal-ligand cooperation allows all of the manganese intermediates to exist in same oxidation state (+1) and plays an important role in these catalytic cross-coupling reactions.

Manganese(I)-Catalyzed α-Alkenylation of Ketones Using Primary Alcohols.

A simple protocol of manganese catalyzed selective α-alkenylation of ketones using primary alcohols is reported. The reactions proceeded well with a low loading of catalyst (0.3 mol %). The overall transformation operates through O-H bond activation of primary alcohols via dearomatization-aromatization metal ligand cooperation in the catalyst to provide the corresponding aldehydes, which further undergo condensation with methylene ketones to deliver α,ß-unsaturated ketones. This selective α-alkenylation proceeds with the release of water and liberation of molecular hydrogen.

Ruthenium(ii)-catalysed direct synthesis of ketazines using secondary alcohols.

Direct one-pot synthesis of ketazines from secondary alcohols and hydrazine hydrate catalyzed by a ruthenium pincer complex is reported, which proceeds through O-H bond activation of secondary alcohols via amine-amide metal-ligand cooperation in the catalyst. Remarkably, liberated molecular hydrogen and water are the only byproducts.