Ruthenium‐Catalyzed Tandem‐Isomerization/Asymmetric Transfer Hydrogenation of Allylic Alcohols

A one‐pot procedure for the direct conversion of racemic allylic alcohols to enantiomerically enriched saturated alcohols is presented. The tandem‐isomerization/asymmetric transfer hydrogenation process is efficiently catalyzed by [{Ru(p‐cymene)Cl₂}₂] in combination with the α‐amino acid hydroxyamide ligand 1 , and performed under mild conditions in a mixture of ethanol and THF. The saturated alcohol products are isolated in good to excellent chemical yields and in enantiomeric excess up to 93 %.     

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.

     

Iridium‐Catalyzed Regio‐ and Enantioselective Hydroarylation of Alkenyl Ethers by Olefin Isomerization

Iridium‐catalyzed hydroarylation of alkenyl ethers, such as allylic and homoallylic ethers, by C−H bond activation gave high yields of the corresponding addition products, where the aryl groups were selectively installed at the α‐carbon atom to the alkoxy group. The reaction involves an isomerization of the alkenyl ethers into the corresponding 1‐alkenyl ethers, which then undergo the regio‐ and enantioselective hydroarylation.     

Additive-Free Isomerization of Allylic Alcohols to Ketones with a Cobalt PNP Pincer Catalyst

Catalytic isomerization of allylic alcohols in ethanol as a green solvent was achieved by using air and moisture stable cobalt (II) complexes in the absence of any additives. Under mild conditions, the cobalt PNP pincer complex substituted with phenyl groups on the phosphorus atoms appeared to be the most active. High rates were obtained at 120 °C, even though the addition of one equivalent of base increases the speed of the reaction drastically. Although some evidence was obtained supporting a dehydrogenation–hydrogenation mechanism, it was proven that this is not the major mechanism. Instead, the cobalt hydride complex formed by dehydrogenation of ethanol is capable of double-bond isomerization through alkene insertion–elimination.     

Synthesis of Heterocycles through Transition‐Metal‐Catalyzed Isomerization Reactions

Metal‐catalyzed isomerization of N‐ and O‐allylic systems is emerging as an effective method to form synthetically useful iminium and oxocarbenium intermediates. In the presence of tethered nucleophiles, several recent examples illuminate this approach as a powerful strategy for the synthesis of structurally complex and diverse heterocycles. In this Concept article, we attempt to cover this area of research through a selection of recent versatile examples.     

Catalytic Regioselective Isomerization of 2,2‐Disubstituted Oxetanes to Homoallylic Alcohols

The selective isomerization of strained heterocyclic compounds is an important tool in organic synthesis. An unprecedented regioselective isomerization of 2,2‐disubstituted oxetanes into homoallylic alcohols is described. The use of tris(pentafluorophenyl)borane (B(C₆F₅)₃)_, a commercially available Lewis acid was key to obtaining good yields and selectivities since other Lewis acids afforded mixtures of isomers and substantial polymerization. The reaction took place under exceptionally mild reaction conditions and very low catalyst loading (0.5 mol %). DFT calculations disclose the mechanistic features of the isomerization and account for the high selectivity displayed by the B(C₆F₅)₃ catalyst. The synthetic applicability of the new reaction is demonstrated by the preparation of γ‐chiral alcohols using iridium‐catalyzed asymmetric hydrogenation.     

Photoredox‐Catalyzed Isomerization of Highly Substituted Allylic Alcohols by C−H Bond Activation

Photoredox‐catalyzed isomerization of γ‐carbonyl‐substituted allylic alcohols to their corresponding carbonyl compounds was achieved for the first time by C?H bond activation. This catalytic redox‐neutral process resulted in the synthesis of 1,4‐dicarbonyl compounds. Notably, allylic alcohols bearing tetrasubstituted olefins can also be transformed into their corresponding carbonyl compounds. Density functional theory calculations show that the carbonyl group at the γ‐position of allylic alcohols are beneficial to the formation of their corresponding allylic alcohol radicals with high vertical electron affinity, which contributes to the completion of the photoredox catalytic cycle.     

Stereoselective Access to Fully Substituted Aldehyde‐Derived Silyl Enol Ethers by Iridium‐Catalyzed Alkene Isomerization

An in situ generated cationic Ir‐catalyst isomerizes simple allylic silyl ethers into valuable, fully substituted aldehyde‐derived silyl enol ethers. Importantly, by judicious choice of substrate, either of the two possible stereoisomers of a given enolate derivative is accessible with complete stereoselectivity. One‐pot isomerization‐aldol and isomerization‐allylation processes illustrate the synthetic utility of this method.     

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.     

Hot Water‐Promoted SN1 Solvolysis Reactions of Allylic and Benzylic Alcohols

During the studies of hydrolysis of epoxides in water, we found that the hydrolysis of (?)‐α‐pinene oxide at 20 °C gave enantiomerically pure trans‐(?)‐sobrerol, whereas the same reaction in water heated at reflux unexpectedly gave a racemic mixture of trans‐ and cis‐sobrerol (trans/cis=6:4). We have examined this remarkable difference in detail and found that hot water, whose behavior is quite different compared with room‐ or high‐temperature water, could promote S_N1 solvolysis reactions of allylic alcohols and thus caused the racemization of trans‐(?)‐sobrerol. The effect of reaction temperature, the addition of organic co‐solvent, and the concentration of the solute on the rate of the racemization of trans‐(?)‐sobrerol were further examined to understand the role that hot water played in the reaction. It was proposed that the catalytic effects of hot water are owing to its mild acidic characteristic, thermal activation, high ionizing power, and better solubility of organic reactant. Further investigation showed that the racemization of other chiral allylic/benzylic alcohols could efficiently proceed in hot water.     

Visible Light‐Promoted Decarboxylative Di‐ and Trifluoromethylthiolation of Alkyl Carboxylic Acids

Described herein is a new and straightforward decarboxylative di‐ and trifluoromethylthiolation of alkyl carboxylic acids promoted by visible light. This approach enables the synthesis of biologically relevant alkyl SCF₂H and SCF₃ compounds from cheap and abundant carboxylic acids. The method is operationally simple, using irradiation from household light sources, and its mild reaction conditions make it tolerant of a range of functional groups. The strategy employs electrophilic phthalimide‐derived di‐ and trifluoromethylthiolation reagents and exploits the ability of the imidyl radical to carry a radical chain.     

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.     

Transition‐Metal‐Free Borylation of Allylic and Propargylic Alcohols

The base‐catalyzed allylic borylation of tertiary allylic alcohols allows the synthesis of 1,1‐disubstituted allyl boronates, in moderate to high yield. The unexpected tandem performance of the Lewis acid–base adduct, [Hbase]⁺[MeO‐B₂pin₂]^? favored the formation of 1,2,3‐triborylated species from the tertiary allylic alcohols and 1‐propargylic cyclohexanol at 90 °C.     

Synthesis of meta‐Functionalized Pyridines by Selective Dehydrogenative Heterocondensation of β‐ and γ‐Amino Alcohols

New reactions that convert alcohols into important classes of compounds are becoming increasingly important as their development contributes to the conservation of our fossil carbon feedstock and the reduction of CO₂ emissions. Two key catalytic alcohol conversion concepts are borrowing hydrogen or hydrogen autotransfer and acceptorless dehydrogenative condensation. Herein, we combined both concepts to synthesize meta ‐functionalized pyridines. First, diols and amines were linked to β‐amino alcohols, which can then undergo a selective dehydrogenative heterocondensation with γ‐amino alcohols. Iridium catalysts stabilized by PN₅P pincer ligands that were developed in our laboratory mediate the reactions most efficiently. All of the 3‐aminopyridines that we describe in this paper have been synthesized for the first time, emphasizing the degree of innovation of this method and the problems associated with the synthesis of such meta ‐functionalized pyridines.