Highly Chemoselective Calcium‐Catalyzed Propargylic Deoxygenation

A calcium‐catalyzed direct reduction of propargylic alcohols and ethers has been accomplished by using triethylsilane as a nucleophilic hydride source. At room temperature a variety of secondary propargylic alcohols was deoxygenated to the corresponding hydrocarbons in excellent yields. Furthermore, for the first time, a catalytic deoxygenation of tertiary propargylic alcohols was generally applicable. The same protocol was suitable for an efficient reduction of secondary as well as tertiary propargylic methyl, benzyl and allyl ethers. Substrates containing an additional keto‐, ester or secondary hydroxyl function were reduced with exceptional chemoselectivity at the propargylic position.     

A Surprising Substituent Effect Provides a Superior Boronic Acid Catalyst for Mild and Metal‐Free Direct Friedel–Crafts Alkylations and Prenylations of Neutral Arenes

The development of more general and efficient catalytic processes for Friedel–Crafts alkylations is an important objective of interest toward the production of pharmaceuticals and commodity chemicals. Herein, 2,3,4,5‐tetrafluorophenylboronic acid was identified as a potent air‐ and moisture‐tolerant metal‐free catalyst that significantly improves the scope of direct Friedel–Crafts alkylations of a variety of slightly activated and neutral arenes, including polyarenes, with allylic and benzylic alcohols. This method also provides a simple alternative for the direct installation of prenyl units commonly found in naturally occurring arenes. Alkylations with benzylic alcohols occur under exceptionally mild conditions.     

Highly Chemoselective Aerobic Oxidation of Amino Alcohols into Amino Carbonyl Compounds

The direct oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has often posed serious challenges in organic synthesis and has constrained chemists to adopting an indirect route, such as a protection/deprotection strategy, to attain their goal. Described herein is a highly chemoselective aerobic oxidation of unprotected amino alcohols to their amino carbonyl compounds in which 2‐azaadamantane N‐oxyl (AZADO)/copper catalysis is used. The catalytic system developed leads to the alcohol‐selective oxidation of various unprotected amino alcohols, carrying a primary, secondary, or tertiary amino group, in good to high yield at ambient temperature with exposure to air, thus offering flexibility in the synthesis of nitrogen‐containing compounds.     

Direct Catalytic Synthesis of Unprotected 2‐Amino‐1‐Phenylethanols from Alkenes by Using Iron(II) Phthalocyanine

Aryl‐substituted amino alcohols are privileged scaffolds in medicinal chemistry and natural products. Herein, we report that an exceptionally simple and inexpensive Fe^II complex efficiently catalyzes the direct transformation of simple alkenes into unprotected amino alcohols in good yield and perfect regioselectivity. This new catalytic method was applied in the expedient synthesis of bioactive molecules and could be extended to aminoetherification.     

Validity of Inorganic Nanosheets as an Efficient Planar Substituent To Enhance the Enantioselectivity of Transition‐Metal‐Catalyzed Asymmetric Synthesis

Effectively enhancing the enantioselectivity is a persistent challenge in heterogeneous asymmetric catalysis. Here, the validity of a layered double hydroxides (LDH) nanosheet as an efficient planar substituent to enhance the enantioselectivity has been investigated theoretically; first in vanadium‐catalyzed asymmetric epoxidation of allylic alcohols, and then in zinc‐catalyzed direct asymmetric aldol addition. The computational predication is further confirmed experimentally in zinc‐catalyzed direct asymmetric aldol addition by controlling the location of catalytic sites.     

Efficient and Simple Approaches Towards Direct Oxidative Esterification of Alcohols

The present article describes novel oxidative protocols for direct esterification of alcohols. The protocols involve successful demonstrations of both “cross” and “self” esterification of a wide variety of alcohols. The cross‐esterification proceeds under a simple transition‐metal‐free condition, containing catalytic amounts of TEMPO (2,2,6,6‐tetramethyl‐1‐piperidinyloxy)/TBAB (tetra‐n‐butylammonium bromide) in combination with oxone (potassium peroxo monosulfate) as the oxidant, whereas the self‐esterification is achieved through simple induction of Fe(OAc)₂/dipic (dipic=2,6‐pyridinedicarboxylic acid) as the active catalyst under an identical oxidizing environment.     

Direct Carbohydroxylation of Arylalkenes with Allylic Alcohols: Cooperative Catalysis of Copper,Silver, and a Brønsted Acid

The cooperative catalysis of copper, silver, and Brønsted acid is presented as a new strategy for olefin functionalization. The catalytic direct carbohydroxylation of arylalkenes with allylic alcohols provided a straightforward and efficient approach for preparing 4,5‐unsaturated alcohols. Synthetically useful functional groups, such as Cl, Br, carbonyl, and chloromethyl, remained intact during the functionalization reaction.     

Direct Carbohydroxylation of Arylalkenes with Allylic Alcohols: Cooperative Catalysis of Copper,Silver, and a Brønsted Acid

The cooperative catalysis of copper, silver, and Brønsted acid is presented as a new strategy for olefin functionalization. The catalytic direct carbohydroxylation of arylalkenes with allylic alcohols provided a straightforward and efficient approach for preparing 4,5‐unsaturated alcohols. Synthetically useful functional groups, such as Cl, Br, carbonyl, and chloromethyl, remained intact during the functionalization reaction.     

Manganese‐Catalyzed Direct Olefination of Methyl‐Substituted Heteroarenes with Primary Alcohols

Herein, we present the first catalytic direct olefination of methyl‐substituted heteroarenes with primary alcohols through an acceptorless dehydrogenative coupling. The reaction is catalyzed by a complex of the earth‐abundant transition metal manganese that is stabilized by a bench‐stable NNN pincer ligand derived from 2‐hydrazinylpyridine. The reaction is environmentally benign, producing only hydrogen and water as byproducts. A large number of E‐disubstituted olefins were selectively obtained with high efficiency.     

Direct Regiospecific and Highly Enantioselective Intermolecular α‐Allylic Alkylation of Aldehydes by a Combination of Transition‐Metal and Chiral Amine Catalysts

The first direct intermolecular regiospecific and highly enantioselective α‐allylic alkylation of linear aldehydes by a combination of achiral bench‐stable Pd⁰ complexes and simple chiral amines as co‐catalysts is disclosed. The co‐catalytic asymmetric chemoselective and regiospecific α‐allylic alkylation reaction is linked in tandem with in situ reduction to give the corresponding 2‐alkyl alcohols with high enantiomeric ratios (up to 98:2 e.r.; e.r.=enantiomeric ratio). It is also an expeditious entry to valuable 2‐alkyl substituted hemiacetals, 2‐alkyl‐butane‐1,4‐diols, and amines. The concise co‐catalytic asymmetric total syntheses of biologically active natural products (e.g., Arundic acid) are disclosed.     

Room‐Temperature Guerbet Reaction with Unprecedented Catalytic Efficiency and Enantioselectivity

We report herein an unprecedented highly efficient Guerbet‐type reaction at room temperature (catalytic TON up to >6000). This β‐alkylation of secondary methyl carbinols with primary alcohols has significant advantage of delivering higher‐order secondary alcohols in an economical, redox‐neutral fashion. In addition, the first enantioselective Guerbet reaction has also been achieved using a commercially available chiral ruthenium complex to deliver secondary alcohols with moderate yield and up to 92 % ee. In both reactions, the use of a traceless ketone promoter proved to be beneficial for the catalytic efficiency.     

A Simple,Broad‐Scope Nickel(0) Precatalyst System for the Direct Amination of Allyl Alcohols

The preparation of allylic amines is traditionally accomplished by reactions of amines with reactive electrophiles, such as allylic halides, sulfonates, or oxyphosphonium species; such methods involve hazardous reagents, generate stoichiometric waste streams, and often suffer from side reactions (such as overalkylation). We report here the first broad‐scope nickel‐catalysed direct amination of allyl alcohols: An inexpensive Ni^II/Zn couple enables the allylation of primary, secondary, and electron‐deficient amines without the need for glove‐box techniques. Under mild conditions, primary and secondary aliphatic amines react smoothly with a range of allyl alcohols, giving secondary and tertiary amines efficiently. This “totally catalytic” method can also be applied to electron‐deficient nitrogen nucleophiles; the practicality of the process was demonstrated in an efficient, gram‐scale preparation of the calcium antagonist drug substance flunarizine (Sibelium®).     

A Simple,Broad‐Scope Nickel(0) Precatalyst System for the Direct Amination of Allyl Alcohols

The preparation of allylic amines is traditionally accomplished by reactions of amines with reactive electrophiles, such as allylic halides, sulfonates, or oxyphosphonium species; such methods involve hazardous reagents, generate stoichiometric waste streams, and often suffer from side reactions (such as overalkylation). We report here the first broad‐scope nickel‐catalysed direct amination of allyl alcohols: An inexpensive Ni^II/Zn couple enables the allylation of primary, secondary, and electron‐deficient amines without the need for glove‐box techniques. Under mild conditions, primary and secondary aliphatic amines react smoothly with a range of allyl alcohols, giving secondary and tertiary amines efficiently. This “totally catalytic” method can also be applied to electron‐deficient nitrogen nucleophiles; the practicality of the process was demonstrated in an efficient, gram‐scale preparation of the calcium antagonist drug substance flunarizine (Sibelium®).     

Commercial Zinc Oxide (Zn2+) as an Efficient and Environmentally Benign Catalyst for Homogeneous Benzoylation of Hydroxyl Functional Groups

The solvent‐free O‐acylation of some alcohols with benzoyl chloride was carried out to the corresponding benzoylated products in good to excellent yields by the mediation of a catalytic amount (5 mol%) of the commercially available and inexpensive zinc oxide in short reaction times. This methodology represents an eco‐friendly and simple catalytic alternative for benzoylation of primary, secondary, tertiary, and benzylic alcohols with ZnO. This catalytic system was homogeneous because of high solubility of zinc oxide in the reaction medium. Findings showed that ZnO was dissolved in hydrochloric acid, created in situ, after a few minutes. Although, others argued on the catalytic role of solid phase zinc oxide under a heterogeneous condition, it is not surprising to emphasize on the catalytic function of Zn²⁺ in the benzoylation of alcohols under homogeneous reaction conditions. Zinc oxide served as pre‐catalyst to form Zn²⁺, as the catalytically active species.     

Direct Olefination of Alcohols with Sulfones by Using Heterogeneous Platinum Catalysts

Carbon‐supported Pt nanoparticles (Pt/C) were found to be effective heterogeneous catalysts for the direct Julia olefination of alcohols in the presence of sulfones and KOtBu under oxidant‐free conditions. Primary alcohols, including aryl, aliphatic, allyl, and heterocyclic alcohols, underwent olefination with dimethyl sulfone and aryl alkyl sulfones to give terminal and internal olefins, respectively. Secondary alcohols underwent methylenation with dimethyl sulfone. Under 2.5 bar H_2, the same reaction system was effective for the transformation of alcohol OH groups to alkyl groups. Structural and mechanistic studies of the terminal olefination system suggested that Pt⁰ sites on the Pt metal particles are responsible for the rate‐limiting dehydrogenation of alcohols and that KOtBu may deprotonate the sulfone reagent. The Pt/C catalyst was reusable after the olefination, and this method showed a higher turnover number (TON) and a wider substrate scope than previously reported methods, which demonstrates the high catalytic efficiency of the present method.     

Catalytic Asymmetric Inverse‐Electron‐Demand Oxa‐Diels–Alder Reaction of In Situ Generated ortho‐Quinone Methides with 3‐Methyl‐2‐Vinylindoles

The first catalytic asymmetric inverse‐electron‐demand (IED) oxa‐Diels–Alder reaction of ortho‐quinone methides, generated in situ from ortho‐hydroxybenzyl alcohols, has been established. By selecting 3‐methyl‐2‐vinylindoles as a class of competent dienophiles, this approach provides an efficient strategy to construct an enantioenriched chroman framework with three adjacent stereogenic centers in high yields and excellent stereoselectivities (up to 99 % yield, >95:5 d.r., 99.5:0.5 e.r.). The utilization of ortho‐hydroxybenzyl alcohols as precursors of dienes and 3‐methyl‐2‐vinylindoles as dienophiles, as well as the hydrogen‐bonding activation mode of the substrates met the challenges of a catalytic asymmetric IED oxa‐Diels–Alder reaction.     

Green and reusable homogeneous oxidative system with ceric ammonium nitrate/[Imim‐PEG1000‐TEMPO] for efficient aerobic oxidation of alcohols and one‐pot synthesis of benzimidazoles from alcohols under ambient conditions

An efficient and reusable catalytic system for aerobic oxidation of alcohols and one‐pot synthesis of benzimidazoles from alcohols with ceric ammonium nitrate and PEG₁₀₀₀–ionic liquid‐immobilized 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) is described. This system shows excellent activity and selectivity, affording the target products with good yields. Moreover, the catalytic system can be recycled and reused without significant loss of catalytic activity after seven runs. Copyright © 2014 John Wiley & Sons, Ltd.     

Pt-Sn/γ-Al2O3-catalyzed highly efficient direct synthesis of secondary and tertiary amines and imines

Versatile syntheses of secondary and tertiary amines by highly efficient direct N‐alkylation of primary and secondary amines with alcohols or by deaminative self‐coupling of primary amines have been successfully realized by means of a heterogeneous bimetallic Pt–Sn/γ‐Al₂O₃ catalyst (0.5 wt % Pt, Pt/Sn molar ratio=1:3) through a borrowing‐hydrogen strategy. In the presence of oxygen, imines were also efficiently prepared from the tandem reactions of amines with alcohols or between two primary amines. The proposed mechanism reveals that an alcohol or amine substrate is initially dehydrogenated to an aldehyde/ketone or NH‐imine with concomitant formation of a [PtSn] hydride. Condensation of the aldehyde/ketone species or deamination of the NH‐imine intermediate with another molecule of amine forms an N‐substituted imine which is then reduced to a new amine product by the in‐situ generated [PtSn] hydride under a nitrogen atmosphere or remains unchanged as the final product under an oxygen atmosphere. The Pt–Sn/γ‐Al₂O₃ catalyst can be easily recycled without Pt metal leaching and has exhibited very high catalytic activity toward a wide range of amine and alcohol substrates, which suggests potential for application in the direct production of secondary and tertiary amines and N‐substituted imines.     

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.     

Highly Regio‐ and Stereodivergent Access to 1,2‐Amino Alcohols or 1,4‐Fluoro Alcohols by NHC‐Catalyzed Ring Opening of Epoxy enals

Described is an unprecedented NHC‐catalyzed (NHC=N‐heterocyclic carbene), stereoselective ring opening of epoxy and cyclopropyl enals to deliver valuable compounds bearing multiple stereocenters. A straightforward three‐step procedure involving two catalytic enantioselective transformations has been developed and leads to a regio‐ and stereodivergent synthesis of either 1,2‐amino alcohols/diamines or 1,4‐fluoro alcohols with excellent diastereo‐ and enantiopurity.