Ruthenium‐Catalyzed β‐Alkylation of Secondary Alcohols with Primary Alcohols

Cyclopentadienyl (Cp), hydrotris(pyrazolyl)borato (Tp), and bipyridine ruthenium complexes were found to be active catalysts for the β‐alkylation of secondary alcohols with primary alcohols. Mechanistic aspects of the Cp and Tp complexes‐catalyzed reactions were investigated; the crucial hydrido complexes were identified. Carbonyl complexes resulting from aldehyde decarbonylation were formed in some cases, and surprisingly, they were also found to be active for the catalytic processes.     

Ruthenium‐Catalyzed Asymmetric Hydrogenation of β‐Keto‐ enamines: An Efficient Approach to Chiral γ‐Amino Alcohols

A highly efficient and enantioselective hydrogenation of unprotected β‐ketoenamines catalyzed with ruthenium(II) dichloro{(S)‐(−)‐2,2′‐bis[di(3,5‐xylyl)phosphino]‐1,1′‐binaphthyl}[(2S)‐(+)‐1,1‐bis(4‐methoxyphenyl)‐3‐methyl‐1,2‐butanediamine] {Ru[(S)‐xylbinap][(S)‐daipen]Cl₂} has been successfully developed. This methodology provides a straightforward access to free γ‐secondary amino alcohols, which are key building blocks for a variety of pharmaceuticals and natural products, with high yields (>99%) and excellent enantioselectivities (up to 99% ee) in all cases.     

Axial Chirality Control by 2,4‐Pentanediol for the Alternative Synthesis of C3*‐TunePhos Chiral Diphosphine Ligands and Their Applications in Highly Enantioselective Ruthenium‐Catalyzed Hydrogenation of β‐Keto Esters

A highly efficient strategy for the synthesis of a series of C₃*‐TunePhos chiral diphosphine ligands was well established with several remarkable features. The synthetic utility of these ligands was explored for the ruthenium‐catalyzed asymmetric hydrogenation of β‐keto esters. Up to 99% ee values were achieved for the enantioselective synthesis of β‐hydroxy acid derivatives, which are very important chiral building blocks for the synthesis of a variety of natural products and biologically active molecules.     

Highly Enantioselective Synthesis of 3‐Hydroxy‐2‐methylpropanoic Acid Esters through Ruthenium‐SYNPHOS®‐Catalyzed Hydrogenation: Useful Building Blocks for the Synthetic Community

Both enantiomers of 3‐hydroxy‐2‐methylpropanoic acid tert‐butyl ester were prepared with high enantioselectivity (up to 94 %) through a ruthenium‐SYNPHOS®‐promoted asymmetric hydrogenation reaction using an atom‐economic transformation from simple and inexpensive precursors.     

Ruthenium‐Catalyzed O‐Allylation of Phenols from Allylic Chlorides via Cationic [Cp*(η3‐allyl)(MeCN)RuX][PF6] Complexes

The [Cp*(MeCN)₃Ru(II)][PF₆] complex is an efficient catalyst precursor for the O‐allylation of phenols with allylic chlorides in the presence of K₂CO₃ under mild conditions. This ruthenium precursor affords branched allyl aryl ethers according to a regioselective reaction, which contrasts with the uncatalyzed nucleophilic substitution from the same substrates. Stable (η³‐allyl)Ru(IV) cationic complexes resulting from the reaction of [Cp*(MeCN)₃Ru][PF₆] with allylic halides were identified as intermediate catalytic species. An X‐ray structure determination of the complex [Cp*(MeCHCHCH₂)(MeCN)RuBr][PF₆] disclosed an (endo‐trans‐MeCHCHCH₂) allylic ligand. The structural information obtained from the study of Cp*(allyl)Ru(IV) complexes indicated that electronic effects at the coordinated allylic ligand likely account for the better regioselectivity obtained from cinnamyl chloride as compared to aliphatic allylic chlorides.     

Ruthenium‐Catalyzed Synthesis of Secondary Alkylamines: Selective Alkylation with Aliphatic Amines

The chemoselective N‐alkylation of tert‐alkylamines applying aliphatic amines is described for the first time. In the presence of the Shvo catalyst 1 , tert‐octylamine 4 and 1‐adamantylamine 5 are alkylated using primary, secondary, and even tertiary amines to give the corresponding monoalkylated tert‐alkylamine in moderate to very good yields and excellent selectivity. This novel reaction proceeds without an additional hydrogen source and ammonia is formed as the only by‐product.     

Acid‐Catalyzed Synthesis of α,β‐Disubstituted Conjugated Enones by a Meyer–Schuster‐Type Rearrangement in Allenols

A novel, direct and simple methodology to gain access to α,β‐disubstituted conjugated enones from α‐allenols in a sustainable metal catalysis context, considering the inexpensiveness and environmentally friendliness of iron(III) species and protons, has been developed.

     

A Ruthenium Complex‐Catalyzed Cyclotrimerization of Halodiynes with Nitriles. Synthesis of 2‐ and 3‐Halopyridines

Monohalo‐ and dihalodiynes efficiently undergo [2+2+2] cyclotrimerization with nitriles in the presence of a catalytic amount of the ruthenium complex Cp*RuCl(cod) (10 mol%) to afford the corresponding halopyridines under ambient conditions in good isolated yields (up to 90%). The halopyridines are formed as two separable regioisomers. This is the first example of a direct synthesis of halopyridines from haloalkynes and nitriles.

     

Gold‐Catalyzed Efficient Formation of α,β‐Unsaturated Ketones from Propargylic Acetates

An efficient gold‐catalyzed method for the preparation of α,β‐unsaturated ketones from propargylic acetates has been developed. Under mild reaction conditions, β‐monosubstituted enones were formed mostly with excellent E‐selectivity. β,β‐Disubstituted enones can be prepared from propargylic acetates derived from ketones. The high efficiency and mild nature of this reaction render it a viable alternative for the synthesis of α,β‐unsaturated ketones.     

Bulky Achiral Triarylphosphines Mimic BINAP in Ru(II)‐ Catalyzed Asymmetric Hydrogenation of Ketones

In the present work, we report on catalysis of the enantioselective hydrogenation of ketones with Ru(II) complexes composed of cheap achiral monodentate phosphine ligands in combination with an enantiopure 1,2‐diamine, affording a variety of optically active secondary alcohols with high efficiency and enantioselectivity. The steric impact of achiral monophosphine ligands in Ru complexes was found to be a critical factor for the high enantioselectivity of the reaction. This finding throws some light on a long‐standing challenge, the high cost of chiral bisphosphine ligands, associated with an industrial application of the asymmetric hydrogenation of ketones.     

Platinum‐Catalyzed Divergent Reactivity of α‐Hydroxyallenes: Synthesis of Dihydrofurans and α,β‐Unsaturated Ketones

α‐Allenols were catalytically transformed into dihydrofurans in the presence of platinum dichloride. Notably, using platinum dichloride along with silver triflate as the catalytic system, α,β‐unsaturated ketones were obtained. Therefore, the role of the silver salt may not just consist in the activation of the platinum precatalyst.

     

Enantioselective Synthesis of Chiral β‐Aryloxy Alcohols by Ruthenium‐Catalyzed Ketone Hydrogenation via Dynamic Kinetic Resolution (DKR)

A highly efficient enantioselective synthesis of chiral β‐aryloxy alcohols by the {RuCl₂[(S)‐SDP][(R,R)‐DPEN]} [(S_a,R,R)‐ 1a ; SDP=7,7′‐bis(diarylphosphino)‐1,1′‐spirobiindane; DPEN=trans‐1,2‐diphenylethylenediamine] complex‐catalyzed asymmetric hydrogenation of racemic α‐aryloxydialkyl ketones via dynamic kinetic resolution (DKR) has been developed. Enantioselectivities of up to 99% ee with good to high cis/anti‐selectivities (up to>99:1) were achieved.     

Anaerobic Palladium‐Catalyzed Chemoselective Oxidation of Allylic and Benzylic Alcohols with α‐Bromo Sulfoxide as a Co‐oxidant

A chemoselective palladium‐catalyzed anaerobic oxidation of allylic and benzylic alcohols using an α‐bromo sulfoxide as a co‐oxidant is described for the first time. The catalyst system is simple and has a long life because of the allowance of phosphane ligands under the non‐aerobic conditions. The advantages of the described method include no overoxidation of primary alcohols to carboxylic acids because of the mild conditions applied, the tolerance of oxygen‐sensitive functionalities such as a carbon‐carbon double bond, an organothio group, or a diorganoamino group and the effective preparation of α,β‐unsaturated aldehydes and ketones, resulting from the oxidation of primary and secondary allylic alcohols, since a competitive Heck reaction with the co‐oxidant does not occur.     

Enantioselective Synthesis of α‐Trifluoromethyl Arylmethylamines by Ruthenium‐Catalyzed Transfer Hydrogenation Reaction

A simple combination of dichloro(para‐cymene)ruthenium(II) dimer, a chiral amino alcohol and isopropyl alcohol allowed for in‐situ generation of the bifunctional catalyst responsible for the transfer hydrogenation reaction of trifluoromethyl ketimines in excellent yields with high enantioselectivities (up to 93% ee). Herein, we describe the optimization, scope, limitations, and applications of the method.

     

A Study of Two Highly Active,Air‐Stable Iron(III)‐μ‐Oxo Precatalysts: Synthetic Scope of Hydrophosphination using Phenyl‐ and Diphenylphosphine

The importance of phosphines in synthetic chemistry cannot be underestimated. Catalytic hydrophosphination offers an ideal method to prepare P−C bonds without the need for harsh reaction conditions or stoichiometric amounts of waste by‐product. We herein report our studies into two biocompatible iron(III) complexes in hydrophosphination chemistry using diphenylphosphine under mild and benign reaction conditions (room temperature, solvent‐free) and our extended exploration of hydrophosphination with phenylphosphine, which can be tuned to operate in the absence of catalyst under thermal conditions for single hydrophosphination or solvent‐free with an iron(III) precatalyst to generate the products of double hydrophosphination.

     

Silver Hexafluoroantimonate‐Catalyzed Direct α‐Alkylation of Unactivated Ketones

A practically simple and direct α‐alkylation of unactivated ketones using benzylic alcohols has been achieved. The in situ formed acetals are the key for the success of the reaction. The catalyst, silver hexafluoroantimonate(V) (AgSbF₆) provides double activation by converting the ketone into an enol ether via acetal and generation of carbocationic center at the benzylic position of the benzylic alcohol. The alcohols include benzylic propargyl alcohols, cinnamyl alcohols, and diarylmethanols.

     

Ruthenium‐Catalyzed Hydroamination of Aminoallenes: an Approach to Vinyl Substituted Heterocycles

Heterosubstituted aminoallenes underwent smooth ruthenium‐catalyzed intramolecular exo‐hydroamination reactions yielding the corresponding five‐, six‐, or seven‐membered 1,3‐diaza‐ or 1,3‐oxaza‐heterocyclic structures. This procedure is a valuable and less expensive alternative to the already known transition metal‐catalyzed hydroamination reactions of aminoallenes.

     

Direct Coupling of Arylacetonitriles and Primary Alcohols to α‐Alkylated Arylacetamides with Complete Atom Economy Catalyzed by a Rhodium Complex–Triphenylphosphine– Potassium Hydroxide System

A direct synthesis of α‐alkylated arylacetamides from arylacetonitriles and primary alcohols has been accomplished for the first time. In the presence of the rhodium complex [Rh(cod)Cl]₂/triphenylphosphine/potassium hydroxide system, the desired α‐alkylated arylacetamides were obtained in 74–92% yield under microwave conditions. The experimental results in this paper are in sharp contrast with previous reports, where the coupling of arylacetonitriles and primary alcohols produced the α‐alkylated arylacetonitriles. Mechanistic investigations show that arylacetonitriles are first α‐alkylated with primary alcohols to produce α‐alkylated arylacetonitriles, which are further hydrated with the water resulting from the α‐alkylation step to produce α‐alkylated arylacetamides. More importantly, this research shows the potential of developing completely atom‐economical reactions that involve the hydrogen autotransfer (or hydrogen borrowing) process.

     

Ruthenium‐Catalyzed Cascade N‐ and C(3)‐Dialkylation of Cyclic Amines with Alcohols Involving Hydrogen Autotransfer Processes

An unprecented N‐ and C(3)‐dialkylation of unactivated amines by a cascade reaction via borrowing hydrogen methodology using new (arene)ruthenium(II) complexes featuring phosphinosulfonate ligands is described. This reaction is highly regioselective and produces water as the only side product.     

Efficient Access to Conjugated Dienones and Diene‐diones from Propargylic Alcohols and Enolizable Ketones: A Tandem Isomerization/Condensation Process Catalyzed by the Sixteen‐Electron Allyl‐Ruthenium(II) Complex [Ru(η3‐2‐C3H4Me)(CO)(dppf)] [SbF6]

A large variety of conjugated dienones R¹R²CCHCHC(R³)C(O)R⁴ and diene‐diones R¹R²CCHCHC{C(O)R³}C(O)R⁴ have been synthesized in high yields by reacting terminal propargylic alcohols HCCCR¹R²(OH) with enolizable ketones R³CH₂C(O)R⁴ and β‐dicarbonyl compounds R³C(O)CH₂C(O)R⁴, respectively. The process, which is catalyzed by the 16e^‐ (η³‐allyl)‐ruthenium(II ) complex [Ru(η³‐2‐C₃H₄Me)(CO)(dppf)] [SbF₆] associated with CF₃CO₂H, involves the initial isomerization of the propargylic alcohol into the corresponding α,β‐unsaturated aldehyde R¹R²CCHCHO (Meyer–Schuster rearrangement) and subsequent aldol‐type condensation.