Ruthenium Catalysts for Controlled Mono‐ and Bis‐Allylation of Active Methylene Compounds with Aliphatic Allylic Substrates

The allylation of 1,3‐dicarbonyl compounds and malononitrile with aliphatic allylic substrates is achieved under mild conditions in the presence of new ruthenium catalysts. The ruthenium complex [Ru(C₅Me₅)(2‐quinolinecarboxylato)(CH₂CHCH‐n‐Pr)] [BF₄] as a precatalyst, allows the synthesis of mono‐allylated branched derivatives. On the other hand, the parent complex [Ru(C₅Me₅)(MeCN)₃] [PF₆] as a precatalyst, straightforwardly favours the bis‐allylation of the procarbonucleophiles leading to bis‐allylated bis‐linear products. The involvement of the two precatalysts provides a sequential synthesis of unsymmetrical mixed linear‐branched bis‐allylated derivatives.     

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.     

Novel [Ruthenium(substituted‐tetramethylcyclopentadiene) (2‐quinolinecarboxylato)(allyl)] Hexafluorophosphate Complexes as Efficient Catalysts for Highly Regioselective Nucleophilic Substitution of Aliphatic Allylic Substrates

Stable [ruthenium(R‐substituted‐tetramethylcyclopentadiene)(2‐quinolinecarboxylato)(1‐R′‐substituted‐allyl) hexafluorophosphate (R=Me, R′=H, Me, n‐Pr, Ph; R=t‐Bu, R′=Me) and [ruthenium(pentamethylcyclopentadiene)(2‐quinolinecarboxylato)(1‐n‐propylallyl)] tetrafluoroborate ( 4′a ), as allylruthenium(IV) complexes, have been synthesized in one step, starting from [ruthenium(R‐substituted‐tetramethylcyclopentadiene)tris(acetonitrile) hexafluorophosphate or tetrafluoroborate complexes, quinaldic acid, and allylic alcohols. Single stereoisomers are obtained and the X‐ray single crystal structure determinations of 3b (R=t‐Bu, R′=Me) and 4′a allow one to specify the preferred arrangement. Complexes 3a (R=R′=Me) and 3b are involved as precatalysts favoring the formation of branched products in regioselective nucleophilic allylic substitution reactions, starting from ethyl 2‐(E)‐hexen‐1‐yl carbonate and chlorohexene as unsymmetrical aliphatic allylic substrates. Phenols, dimethyl malonate, and primary (aniline) and secondary (pyrrolidine, piperidine) amines have been used as nucleophiles under mild basic conditions. For the first time, the regioselectivity in favor of the branched product obtained from purely aliphatic allylic substrates is close to the high regioselectivity previously reached starting from cinnamyl‐type substrates in the presence of ruthenium catalysts.     

Ruthenium Pincer‐Catalyzed Acylation of Alcohols Using Esters with Liberation of Hydrogen under Neutral Conditions

Acylation of secondary alcohols using non‐activated esters, in particular symmetrical esters (such as ethyl acetate), is achieved under neutral conditions with the liberation of molecular hydrogen. This unprecedented, environmentally benign reaction is homogenously catalyzed by a dearomatized ruthenium pincer PNN complex.     

Palladium/Brønsted Acid‐Catalyzed α‐Allylation of Aldehydes with Allylic Alcohols

A simple, highly efficient, and readily scalable direct α‐allylation of aldehydes with allylic alcohols that is co‐catalyzed by palladium and a Brønsted acid has been developed.     

Cationic Ruthenium‐Cyclopentadienyl‐Diphosphine Complexes as Catalysts for the Allylation of Phenols with Allyl Alcohol; Relation between Structure and Catalytic Performance in O‐ vs. C‐Allylation

A new catalytic method has been investigated to obtain either O‐ or C‐allylated phenolic products using allyl alcohol or diallyl ether as the allyl donor. With the use of new cationic ruthenium(II) complexes as catalyst, both reactions can be performed with good selectivity. Active cationic Ru(II) complexes, having cyclopentadienyl and bidentate phosphine ligands are generated from the corresponding Ru(II) chloride complexes with a silver salt. The structures of three novel (diphosphine)Ru(II)CpCl catalyst precursor complexes are reported. It appears that the structure of the bidentate ligand has a major influence on catalytic activity as well as chemoselectivity. In addition, a strong cocatalytic effect of small amounts of acid is revealed. Model experiments are described that have been used to build a reaction network that explains the origin and evolution in time of both O‐allylated and C‐allylated phenolic products. Some mechanistic implications of the observed structure vs. performance relation of the [(diphosphine)RuCp]⁺ complexes and the cocatalytic role of added protons are discussed.     

Ruthenium Pincer‐Catalyzed Cross‐Dehydrogenative Coupling of Primary Alcohols with Secondary Alcohols under Neutral Conditions

Cross‐dehydrogenative coupling of primary alcohols with secondary alcohols to obtain mixed esters with the liberation of molecular hydrogen is achieved in high yield and good selectivity under neutral conditions, using a bipyridyl‐based PNN ruthenium(II) pincer catalyst.     

(Cyclopentadienyl)ruthenium‐Catalyzed Regio‐ and Enantioselective Decarboxylative Allylic Etherification of Allyl Aryl and Alkyl Carbonates

(Cyclopentadienyl)tris(acetonitrile)ruthenium hexafluorophosphate {[CpRu(NCMe)₃][PF₆]} or (cyclopentadienyl)(η⁶‐naphthalene)ruthenium hexafluorophosphate {[CpRu(η⁶‐naphthalene)][PF₆]} in combination with a pyridine oxazoline ligand efficiently catalyze the decarboxylative allylic rearrangement of allyl aryl carbonates. Good levels of regio‐ and enantioselectivity are obtained. Starting from enantioenriched secondary carbonates, the reaction is stereospecific and the corresponding allylic ethers are obtained with net retention of configuration. An intermolecular version of this transformation was also developed using allyl alkyl carbonates as substrates. Conditions were found to obtain the corresponding products with similar selectivity as in the intramolecular process. Through the use of a hemi‐labile hexacoordinated phosphate counterion, a zwitterionic air‐ and moisture‐stable chiral ruthenium complex was synthesized and used in the enantioselective etherification reactions. This highly lipophilic metal complex can be recovered and efficiently reused in subsequent catalysis runs.     

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.     

Ruthenium(II)‐Catalyzed Regioselective Synthesis of Allyl Ketones from Alkynes and their Silver(I)‐Catalyzed Hydroarylation into γ‐Functionalized Ketones

The regioselective synthesis of β,γ‐unsaturated ketones from terminal alkynes is achieved by cooperative action of tris(acetonitrile)pentamethylcyclopentadieneruthenium hexafluorophosphate [Cp*Ru(NCMe)₃⁺ PF₆⁻] and para‐toluenesulfonic acid catalysts. These allyl ketones undergo direct regioselective hydroarylation/Friedel–Crafts reaction to introduce an electron‐rich aryl group at the γ‐position in the presence of ligand‐free silver triflate (AgOTf) catalyst. Both catalytic reactions take place with atom economy and provide an alternative to the synthesis of a variety of allyl ketones and γ‐arylated ketones.     

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.

     

Relay Catalysis: Enantioselective Synthesis of Cyclic Benzo‐Fused Homoallylic Alcohols by Chiral Brønsted Acid‐Catalyzed Allylboration/Ring Closing Metathesis

Six‐ and seven‐membered benzo‐fused cyclic homoallylic alcohols can be readily synthesized by a tandem chiral Brønsted acid‐catalyzed allyl (crotyl)boration/ring closing metathesis sequence performed under orthogonal relay catalysis conditions. Excellent enantio‐ and diastereoselectivities are obtained in most of the cases. In addition, the parent crotylboration/RCM process is also described. The required substrates, ortho‐vinylbenzaldehydes, are readily available in one step from commercially available starting materials. Both catalysts and reactants are also available from commercial suppliers. The reaction shows broad functional group compatibility and is also suitable for heteroaromatic substrates. Substitution at any position of the aromatic ring is tolerated; however, substitution at position 6 results in a substantial drop in enantioselectivity.     

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.     

Ruthenium(II)‐Catalyzed Oxidant‐Free C–H Olefination of Aromatic Carboxamides with Allyl Acetate

An inexpensive ruthenium‐catalyzed direct C–H olefination of aromatic carboxamides with allyl acetate was developed. This external oxidant‐free protocol provided an efficient route for the synthesis of useful trans‐styrene derivatives in high to excellent yields. The olefination reaction exhibited excellent regioselectivities and allowed the presence of a wide range of functional groups, such as OMe, F, Cl, Br, I, CF₃, NMe₂, as well as NO₂.

     

Enantioselective Phase‐Transfer Catalytic α‐Benzylation and α‐Allylation of α‐tert‐Butoxycarbonyllactones

A new enantioselective α‐benzylation and α‐allylation of α‐tert‐butoxycarbonyllactones was devloped. α‐Benzylation and α‐allylation of α‐tert‐butoxycarbonylbutyrolactone and α‐tert‐butoxycarbonylvalerolactone under phase‐transfer catalytic conditions (50% cesium hydroxide, toluene, −60 °C) in the presence of (S,S)‐3,4,5‐trifluorophenyl‐NAS bromide (1 mol%) afforded the corresponding α‐substituted α‐tert‐butoxycarbonyllactones in very high chemical yields (up to 99%) and optical yields (up to 99% ee). The synthetic potential of this method has been successfully demonstrated by the asymmetric synthesis of unnatural α‐quaternary homoserines, 3‐alkyl‐3‐carboxypyrrolidine and 3‐alkyl‐3‐carboxypiperidine.     

Palladium‐Catalyzed Oxidative Heck‐Type Allylation of β,β‐Disubstituted Enones with Allyl Carbonates

The palladium‐catalyzed oxidative Heck‐type allylation of β,β‐disubstituted enones, i.e., α‐oxoketene dithioacetals, was efficiently realized with allyl carbonates, providing a concise route to highly functionalized dienes. The present synthetic methodology utilizes the substrate activation strategy to activate the C H bond of β,β‐disubstituted enones by introduction of a 1,2‐dithiolane functionality to make the enone substrate highly polarized and thus increase its reactivity, demonstrating rare examples for transition metal‐catalyzed allylic substitution of ß,ß‐disubstituted enones through a Heck‐type allylation process.

     

Highly Selective Cobalt‐Catalyzed Hydrovinylation of Styrene

Phosphine complexes of cobalt halide salts activated by diethylaluminum chloride are shown to yield highly active catalysts in the hydrovinylation of styrene, with unprecedented high selectivity to the desired product 3‐phenyl‐1‐butene (3P1B). Double‐bond isomerization, a common problem in codimerization reactions, only occurs after full conversion with these catalyst systems, even at elevated temperature. The most active catalysts are based on cobalt halide species combined with either C₁‐ or C₂‐bridged diphosphines, heterodonor P,N or P,O ligands, flexible bidentate phosphine ligands or monodentate phosphine ligands. Kinetic investigations show an order >1 in catalyst, which indicates either the involvement of dinuclear species in the catalytic cycle or partial catalyst decomposition via a bimolecular pathway.     

[CpRu(IV)(π‐C3H5)(2‐quinolinecarboxylato)]PF6 Complex: A Robust Catalyst for the Cleavage and Formation of Allyl Ethers

A facile and efficient method for the quantitative synthesis of [CpRu(IV)(π‐C₃H₅)(2‐quinolinecarboxylato)]PF₆ from [CpRu(CH₃CN)₃]PF₆, 2‐quinolinecarboxylic acid, and 2‐propen‐1‐ol has been established. The cationic Ru(IV) complex is air‐ and moisture‐stable, and can be stored in a vial for at least six months. This complex realizes a simple and easy operation for both the deallylation of allyl ethers in methanol and the dehydrative allylation of alcohols. Furthermore, with removal of the volatile allyl methyl ether co‐product from the reaction system, the robust catalyst can attain a turnover of 10000 cycles of allyl ether cleavage.     

Copper‐Catalyzed Oxidative Transformation of Secondary Alcohols to 1,5‐Disubstituted Tetrazoles

A mild and convenient oxidative transformation of secondary alcohols to 1,5‐disubstituted tetrazoles is uncovered by employing trimethylsilyl azide (TMSN₃) as a nitrogen source in the presence of a catalytic amount of copper(II) perchlorate hexahydrate [Cu(ClO₄)₂^.6 H₂O] (5 mol%) and 2,3‐dichloro‐5,6‐dicyano‐para‐benzoquinone (DDQ) (1.2 equiv.) as an oxidant. This reaction is performed under ambient conditions and proceeds through C C bond cleavage.