Iridium‐Catalyzed Dehydrogenative Decarbonylation of Primary Alcohols with the Liberation of Syngas

A new iridium ‐ catalyzed reaction in which molecular hydrogen and carbon monoxide are cleaved from primary alcohols in the absence of any stoichiometric additives has been developed. The dehydrogenative decarbonylation was achieved with a catalyst generated in situ from [Ir(coe)₂Cl]₂ (coe=cyclooctene) and racemic 2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl (rac‐BINAP) in a mesitylene solution saturated with water. A catalytic amount of lithium chloride was also added to improve the catalyst turnover. The reaction has been applied to a variety of primary alcohols and gives rise to products in good to excellent yields. Ethers, esters, imides, and aryl halides are stable under the reaction conditions, whereas olefins are partially saturated. The reaction is believed to proceed by two consecutive organometallic transformations that are catalyzed by the same iridium(I)–BINAP species. First, dehydrogenation of the primary alcohol to the corresponding aldehyde takes place, which is then followed by decarbonylation to the product with one less carbon atom.     

Iridium‐Catalyzed Asymmetric Hydrogenation of 3,3‐Disubstituted Allylic Alcohols in Ethereal Solvents

Ir‐phosphinomethyl‐oxazoline complexes have been identified as efficient, highly enantioselective catalysts for the asymmetric hydrogenation of 3,3‐disubstituted allylic alcohols and related homoallylic alcohols. In contrast to other N,P ligand complexes, which require weakly coordinating solvents, such as dichloromethane, these catalysts perform well in more ecofriendly THF or 2‐MeTHF. Their synthetic potential was demonstrated with the formal total synthesis of four bisabolane sesquiterpenes.     

Iridium‐Catalyzed Asymmetric Isomerization of Primary Allylic Alcohols

Nothing to sm(Ir)k at : Under appropriate reaction conditions, iridium hydride catalysts promote the isomerization of primary allylic alcohols. The best catalysts, like (R)‐ 1 (P green, O red, N blue, Ir yellow), deliver the desired chiral aldehydes with excellent enantioselectivity and good yields. Mechanistic hypotheses have been developed on the basis of preliminary investigations.

     

Ruthenium‐Catalyzed Oxidation of Alkenes,Alkynes, and Alcohols to Organic Acids with Aqueous Hydrogen Peroxide

A protocol that adopts aqueous hydrogen peroxide as a terminal oxidant and [(Me₃tacn)(CF₃CO₂)₂Ru^III(OH₂)]CF₃CO₂ ( 1 ; Me₃tacn=1,4,7‐trimethyl‐1,4,7‐triazacyclononane) as a catalyst for oxidation of alkenes, alkynes, and alcohols to organic acids in over 80 % yield is presented. For the oxidation of cyclohexene to adipic acid, the loading of 1 can be lowered to 0.1 mol %. On the one‐mole scale, the oxidation of cyclohexene, cyclooctene, and 1‐octanol with 1 mol % of 1 produced adipic acid (124 g, 85 % yield), suberic acid (158 g, 91 % yield), and 1‐octanoic acid (129 g, 90 % yield), respectively. The oxidative C?C bond‐cleavage reaction proceeded through the formation of cis‐ and trans‐diol intermediates, which were further oxidized to carboxylic acids via C? C bond cleavage.     

Gold(I)‐Catalyzed Diastereoselective Hydroacylation of Terminal Alkynes with Glyoxals

The reaction of an α‐ketoaldehyde and a terminal alkyne in the presence of piperidine and a catalytic amount of AuCl delivers 1,2‐dicarbonyl‐3‐enes, products of the formal hydroacylation of the triple bond. The scope of the method is broad; different aryl substituents on the dicarbonyl unit and on the alkyne are well tolerated. The products can be transformed selectively into vinylquinoxalines. Mechanistic studies, including isotope‐labeling experiments, indicate that after an initial A³‐type conversion to propargylic amines, a subsequent base‐mediated alkyne‐to‐allene isomerization and a hydrolysis of the enamine substructure during the workup deliver the formal hydroacylation products.     

Cobalt‐Catalyzed Annulation of Salicylaldehydes and Alkynes to Form Chromones and 4‐Chromanones

A unique cobalt(I)–diphosphine catalytic system has been identified for the coupling of salicylaldehyde (SA) and an internal alkyne affording a dehydrogenative annulation product (chromone) or a reductive annulation product (4‐chromanone) depending on the alkyne substituents. Distinct from related rhodium(I)‐ and rhodium(III)‐catalyzed reactions of SA and alkynes, these annulation reactions feature aldehyde C?H oxidative addition of SA and subsequent hydrometalation of the C=O bond of another SA molecule as common key steps. The reductive annulation to 4‐chromanones also involves the action of Zn as a stoichiometric reductant. In addition to these mechanistic features, the Co^I catalysis described herein is complementary to the Rh^I‐ and Rh^III‐catalyzed reactions of SA and internal alkynes, particularly in the context of chromone synthesis.     

Rhodium‐ and Iridium‐Catalyzed Asymmetric Addition of Optically Pure P‐Chiral H‐Phosphinates to Aldehydes Leading to Optically Active α‐Hydroxyphosphinates

Optically active α‐hydroxyphosphinates with both C‐ and P‐stereogenic centers are obtained by rhodium‐ or iridium‐catalyzed substrate‐directed stereoselective addition of the optically pure H‐phosphinates to aldehydes. The reaction most probably proceeds by a transition‐metal‐catalyzed mechanism with hydridometal complexes as key intermediates in the catalytic cycle.     

Simple and Efficient Ruthenium‐Catalyzed Oxidation of Primary Alcohols with Molecular Oxygen

Oxidative transformations utilizing molecular oxygen (O₂) as the stoichiometric oxidant are of paramount importance in organic synthesis from ecological and economical perspectives. Alcohol oxidation reactions that employ O₂ are scarce in homogeneous catalysis and the efficacy of such systems has been constrained by limited substrate scope (most involve secondary alcohol oxidation) or practical factors, such as the need for an excess of base or an additive. Catalytic systems employing O₂ as the “primary” oxidant, in the absence of any additive, are rare. A solution to this longstanding issue is offered by the development of an efficient ruthenium‐catalyzed oxidation protocol, which enables smooth oxidation of a wide variety of primary, as well as secondary benzylic, allylic, heterocyclic, and aliphatic, alcohols with molecular oxygen as the primary oxidant and without any base or hydrogen‐ or electron‐transfer agents. Most importantly, a high degree of selectivity during alcohol oxidation has been predicted for complex settings. Preliminary mechanistic studies including ¹⁸O labeling established the in situ formation of an oxo–ruthenium intermediate as the active catalytic species in the cycle and involvement of a two‐electron hydride transfer in the rate‐limiting step.     

Palladium‐Catalyzed Formal Hydroalkylation of Aryl‐Substituted Alkynes with Hydrazones

We have developed an unprecedented Pd‐catalyzed formal hydroalkylation of alkynes with hydrazones, which are generated in situ from naturally abundant aldehydes, as both alkylation reagents and hydrogen donors. The hydroalkylation proceeds with high regio‐ and stereoselectivity to form (Z)‐alkenes, which are more difficult to generate compared to (E)‐alkenes. The reaction is compatible with a wide range of functional groups, including hydroxy, ester, ketone, nitrile, boronic ester, amine, and halide groups. Furthermore, late‐stage modifications of natural products and pharmaceutical derivatives exemplify its unique chemoselectivity, regioselectivity, and synthetic applicability. Mechanistic studies indicate the possible involvement of Pd‐hydride intermediates.     

Nickel‐Catalyzed Allylmethylation of Alkynes with Allylic Alcohols and AlMe3: Facile Access to Skipped Dienes and Trienes

We present herein an unprecedented allylative dicarbofunctionalization of alkynes with allylic alcohols. This simple catalytic procedure utilizes commercially available Ni(COD)₂, triphenylphosphine, and inexpensive reagents, and delivers valuable skipped dienes and trienes with an all‐carbon tetrasubstituted alkene unit in a highly stereoselective fashion. Preliminary mechanistic studies support the reaction pathway of allylnickelation followed by transmetalation in this dicarbofunctionalization of alkynes.     

The Synthesis of Benzimidazoles and Quinoxalines from Aromatic Diamines and Alcohols by Iridium‐Catalyzed Acceptorless Dehydrogenative Alkylation

Benzimidazoles and quinoxalines are important N‐heteroaromatics with many applications in pharmaceutical and chemical industry. Here, the synthesis of both classes of compounds starting from aromatic diamines and alcohols (benzimidazoles) or diols (quinoxalines) is reported. The reactions proceed through acceptorless dehydrogenative condensation steps. Water and two equivalents of hydrogen are liberated in the course of the reactions. An Ir complex stabilized by the tridentate P^N^P ligand N²,N⁶‐bis(di‐isopropylphosphino)pyridine‐2,6‐diamine revealed the highest catalytic activity for both reactions.     

Iridium‐Catalyzed Intermolecular Asymmetric Dearomatization of β‐Naphthols with Allyl Alcohols or Allyl Ethers

An Ir‐catalyzed intermolecular asymmetric dearomatization reaction of β‐naphthols with allyl alcohols or allyl ethers was developed. When an iridium catalyst generated from [Ir(COD)Cl]₂ (COD=cyclooctadiene) and a chiral P/olefin ligand is employed, highly functionalized β‐naphthalenone compounds bearing an all‐carbon‐substituted quaternary chiral center were obtained in up to 92 % yield and 98 % ee . The direct utilization of allyl alcohols as electrophiles represents an improvement from the viewpoint of atom economy. Allyl ethers were found to undergo asymmetric allylic substitution reaction under Ir catalysis for the first time. The diverse transformations of the dearomatized product to various motifs render this method attractive.     

Cationic Iridium/Chiral Bisphosphine‐Catalyzed Enantioselective Hydroacylation of Ketones

A facile and convenient synthesis of the chiral phthalide framework catalyzed by cationic iridium was developed. The method utilized cationic iridium/bisphosphine‐catalyzed asymmetric intramolecular carbonyl hydroacylation of 2‐keto benzaldehydes to furnish the corresponding optically active phthalide products in good to excellent enantioselectivities (up to 98% ee). The mechanistic studies using a deuterium‐labelled substrate suggested that the reaction involved an intramolecular carbonyl insertion mechanism to iridium hydride intermediate. In addition, we investigated the kinetic isotope effect (KIE) of intramolecular hydroacylation with deuterated substrate and determined that the C?H activation step is not included in the turnover‐limiting step.     

Iridium‐Catalyzed Arylative Cyclization of Alkynones by 1,4‐Iridium Migration

1,4‐Metal migrations enable the remote functionalization of C? H bonds, and have been utilized in a wide variety of valuable synthetic methods. The vast majority of existing examples involve the 1,4‐migration of palladium or rhodium. Herein, the stereoselective synthesis of complex polycycles by the iridium‐catalyzed arylative cyclization of alkynones with arylboronic acids is described. To our knowledge, these reactions involve the first reported examples of 1,4‐iridium migration.     

Palladium‐Catalyzed Reductive Coupling Reaction of Terminal Alkynes with Aryl Iodides Utilizing Hafnocene Difluoride as a Hafnium Hydride Precursor Leading to trans‐Alkenes

Herein, we describe a reductive cross‐coupling of alkynes and aryl iodides by using a novel catalytic system composed of a catalytic amount of palladium dichloride and a promoter precursor, hafnocene difluoride (Cp₂HfF₂, Cp=cyclopentadienyl anion), in the presence of a mild reducing reagent, a hydrosilane, leading to a one‐pot preparation of trans‐alkenes. In this process, a series of coupling reactions efficiently proceeds through the following three steps: (i) an initial formation of hafnocene hydride from hafnocene difluoride and the hydrosilane, (ii) a subsequent hydrohafnation toward alkynes, and (iii) a final transmetalation of the alkenyl hafnium species to a palladium complex. This reductive coupling could be chemoselectively applied to the preparation of trans‐alkenes with various functional groups, such as an alkyl group, a halogen, an ester, a nitro group, a heterocycle, a boronic ester, and an internal alkyne.