The “Borrowing Hydrogen Strategy” by Supported Ruthenium Hydroxide Catalysts: Synthetic Scope of Symmetrically and Unsymmetrically Substituted Amines

The N‐alkylation of ammonia (or its surrogates, such as urea, NH₄HCO₃, and (NH₄)₂CO₃) and amines with alcohols, including primary and secondary alcohols, was efficiently promoted under anaerobic conditions by the easily prepared and inexpensive supported ruthenium hydroxide catalyst Ru(OH)_x/TiO₂. Various types of symmetrically and unsymmetrically substituted “tertiary” amines could be synthesized by the N‐alkylation of ammonia (or its surrogates) and amines with “primary” alcohols. On the other hand, the N‐alkylation of ammonia surrogates (i.e., urea and NH₄HCO₃) with “secondary” alcohols selectively produced the corresponding symmetrically substituted “secondary” amines, even in the presence of excess amounts of alcohols, which is likely due to the steric hindrance of the secondary alcohols and/or secondary amines produced. Under aerobic conditions, nitriles could be synthesized directly from alcohols and ammonia surrogates. The observed catalysis for the present N‐alkylation reactions was intrinsically heterogeneous, and the retrieved catalyst could be reused without any significant loss of catalytic performance. The present catalytic transformation would proceed through consecutive N‐alkylation reactions, in which alcohols act as alkylating reagents. On the basis of deuterium‐labeling experiments, the formation of the ruthenium dihydride species is suggested during the N‐alkylation reactions.     

InBr3 as a versatile and highly efficient catalyst for the synthesis of 3-allyl- and 3-benzylindoles

Indoles undergo smooth alkylation with allylic and benzylic alcohols in the presence of 10 mol % of InBr₃ under mild conditions to produce 3-allyl- and 3-benzyl indoles, respectively, in excellent yields and with high selectivity. This is the first example of the alkylation of indoles with benzylic alcohols using InBr₃ as an acid catalyst.     

Unprecedented alkylation of silicon enolates with alcohols via carbenium ion formations catalyzed by tin hydroxide-embedded montmorillonite

The solid acid, tin hydroxide-embedded montmorillonite, catalyzes the unprecedented alkylation of various silicon enolates with primary, secondary and tertiary benzylic alcohols as well as secondary allylic alcohols. The acid catalysis of Sn-Mont was not only higher than that of the other ion-exchanged montmorillonites (M-Mont; M = H, Ti, Fe and Al), but also higher than that of the typical homogeneous acid catalysts such as BF₃·OEt₂, TMSOTf and TfOH.     

Solid-phase synthesis of cyclic polyamines

A method for the synthesis of cyclic polyamines based on solid-phase chemistry is shown. Linear polyamines are stepwise synthesized on solid support from the center by repetitive alkylations at benzylic N-atoms. Cyclizations at the resins were effected conventionally by direct intramolecular S_N2 reactions between sulfonyl-protected terminal amino groups and primary alkyl bromides or by intramolecular Mitsunobu reactions between sulphonamides and primary alcohols. Particularly the latter transformation proved to be powerful for the construction of medium- as well as large-sized rings.     

硫酸亚铈催化的芳香化合物与苄基醇、烯丙醇类化合物以及苄基氯的傅-克烷基化反应研究

硫酸亚铈作为一种便宜的和有效的催化剂催化芳香化合物与苄基醇、烯丙醇类化合物和苄基氯的傅-克烷基化反应. 在1～10 mol%的硫酸亚铈存在下, 芳香化合物分别与苄基醇、烯丙醇类化合物和苄基氯能够顺利有效地进行傅-克烷基化反应. 此外, 催化剂能回收, 再次使用三次也没有明显地失去催化活性.     

A BINOL-terpyridine-based multi-task catalyst for a sequential oxidation and asymmetric alkylation of alcohols

Treatment of a BINOL-terpyridine compound with RuCl₃ generates a Ru(II) complex (R)-6. This complex is found to be a novel multi-task catalyst capable of conducting a sequential oxidation and asymmetric alkyl addition to convert primary alcohols to chiral secondary alcohols. The terpyridine-Ru(II) site of (R)-6 catalyzes an efficient oxidation of primary alcohols to aldehydes which then undergo an enantioselective alkylation to generate chiral secondary alcohols when the BINOL site of (R)-6 is combined with ZnEt₂ and Ti(OⁱPr)₄.     

Reaction of 2,7-dialkyl- and 1,2.7-trialkyldecahydro-4-quinolones with triethylaluminum

The reaction of triethylaluminum with stereoisomeric 2,7-dimethyl- and 1,2,7-trimethyldecahydro-4-quinolones and their 7-tert-butyl-substituted analogs was studied. The reaction of triethylaluminum with ketones that have an equatorial 2-CH₃ group proceeds in two directions — reduction of the carbonyl group to an alcohol group and alkylation to give tertiary 4-ethyl-substituted alcohols — in benzene. depending on the reagent ratio. The stereochemistry of the reduction of the carbonyl group depends on the temperature. Only an alkylation product is formed in tetrahydrofuran (THF) and diethyl ether. The reaction of triethylaluminum with ketones that have an axial 2-CH₃ group depends on the nature of the solvent. Epimeric secondary alcohols are formed in toluene at various ratios of the reacting substances, whereas tertiary ethyl-substituted alcohols are formed in THF and diethyl ether.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 946–952, July, 1976.     

Oxidation and β‐Alkylation of Alcohols Catalysed by Iridium(I) Complexes with Functionalised N‐Heterocyclic Carbene Ligands

The borrowing hydrogen methodology allows for the use of alcohols as alkylating agents for C?C bond forming processes offering significant environmental benefits over traditional approaches. Iridium(I)‐cyclooctadiene complexes having a NHC ligand with a O‐ or N‐functionalised wingtip efficiently catalysed the oxidation and β‐alkylation of secondary alcohols with primary alcohols in the presence of a base. The cationic complex [Ir(NCCH₃)(cod)(MeIm(2‐ methoxybenzyl))][BF₄] (cod=1,5‐cyclooctadiene, MeIm=1‐methylimidazolyl) having a rigid O‐functionalised wingtip, shows the best catalyst performance in the dehydrogenation of benzyl alcohol in acetone, with an initial turnover frequency (TOF₀) of 1283 h^?1, and also in the β‐alkylation of 2‐propanol with butan‐1‐ol, which gives a conversion of 94 % in 10 h with a selectivity of 99 % for heptan‐2‐ol. We have investigated the full reaction mechanism including the dehydrogenation, the cross‐aldol condensation and the hydrogenation step by DFT calculations. Interestingly, these studies revealed the participation of the iridium catalyst in the key step leading to the formation of the new C?C bond that involves the reaction of an O‐bound enolate generated in the basic medium with the electrophilic aldehyde.     

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.     

Diethoxyphosphoryl as a Protecting‐Activating Group in the Synthesis of Polyazacyclophanes

The fully diethoxyphosphoryl(Dep)‐protected polyamines 1b – 3b were prepared from the corresponding polyamines with `diethyl phosphite' (=diethyl phosphonate) and CCl₄ in a solid base/organic liquid two‐phase system in the presence of Bu₄NBr as phase‐transfer catalyst. Subsequent phase‐transfer‐catalyzed alkylation of phosphoramidates 1b – 3b with bis(chloromethyl)arenes 5 – 8 in the presence of Bu₄N(HSO₄) followed by deprotection gave good yields of polyazacyclophanes 9a – 16a .     

An Improved Ruthenium Catalyst for the Environmentally Benign Amination of Primary and Secondary Alcohols

The N‐alkylation of amines in the presence of different ruthenium catalysts generated in situ was investigated. Among the various catalysts tested, the combination of [Ru₃(CO)₁₂] and N‐phenyl‐2‐(dicyclohexylphosphanyl)pyrrole showed the best performance. By applying this novel catalyst, a variety of functionalized alcohols and amines were converted into the corresponding secondary amines in high yield.     

An Al(OTf)3-catalyzed environmentally benign process for the propargylation of indoles

Al(OTf)₃ catalyzed the alkylation of indoles using secondary/tertiary propargylic alcohols to produce 3-propargylated indoles in excellent yields with high selectivity. The reactions were performed in air with commercial grade solvents, and water was the only side product of the process. The catalyst was recovered after completion of the reaction and re-used with minimum loss of activity over three cycles.     

Cs2CO3-catalyzed alkylation of indoles with trifluoromethyl ketones

A Cs₂CO₃-catalyzed alkylation reaction of indoles with trifluoromethyl ketones was presented. Both alicyclic and aromatic trifluoromethyl ketones as well as various substituted indoles are compatible with the methodology. Good to excellent yields of the corresponding trifluoromethyl substituted tertiary alcohols 2,2,2-tritrifluoro-1-(1H-indol-3-yl)-ethan-1-ols were acquired as the sole products.     

Steric effects in synthesis—steric limits to the alkylation of nitriles and carboxylic acids

The steric limits to the alkylation of aliphatic nitriles and carboxylic acids have been investigated in some detail. For the experimental conditions considered (ionization by i-Pr₂NLi in THF followed by alkylation with RI/THF/HMPA) the most hindered nitriles R-CN and carboxylic acids R-CO₂H have the same secondary alkyi group RtBuPⁱCH-, but different tertiary. i.e. Rt-BuPrⁱEtC- or i-Pr₃C- for RCN and REt₂MeC for RCO₂H. A comparison of the relative merits of alkylation of esters, carboxylic acids, and nitriles is considered.     

trans-hydroalumination/alkylation: one-pot synthesis of trisubstituted allylic alcohols

[reaction: see text] Described herein is a method of stereoselective synthesis of trisubstituted allylic alcohols by alkylation of alkenyl alanates, formed in situ through treatment of propargyl alcohols with Vitride (Red-Al). This technique represents the first of its kind to feature a trans-hydrometalation, and is particularly effective for the formation of 1,4-dienes. Applications involving primary, secondary, and tertiary alcohols are discussed, as well as limitations regarding both alkyne and electrophile components.     

LiClO4-Activated stereo- and regioselective alkylation of aldehydes

Aldehydes undergo an unusual and very mild alkylation by LiClO₄-activation in the presence of acids. This new methodology enables the inclusion of a broad range of aldehydes as well as tertiary alcohols. Regio- and stereoselectivity observed during this reaction will be discussed.     

An FeCl3-catalyzed highly C3-selective Friedel-Crafts alkylation of indoles with alcohols

The FeCl₃-catalyzed C3-selective Friedel-Crafts alkylation of indoles using allylic, benzylic and propargylic alcohols has been developed. The reaction was performed in the presence of a catalytic amount of inexpensive anhydrous FeCl₃ (10 mol %) in nitromethane under mild conditions. This method can also be used for the alkylation of pyrrole.     

Iron‐Catalyzed α‐Alkylation of Ketones with Alcohols

A general and benign iron‐catalyzed α‐alkylation reaction of ketones with primary alcohols has been developed. The key to success of the reaction is the use of a Knölker‐type complex as catalyst (2 mol %) in the presence of Cs₂CO₃ as base (10 mol %) under hydrogen‐borrowing conditions. Using 2‐aminobenzyl alcohol as alkylation reagent allows for the “green” synthesis of quinoline derivatives.     

A Proton-Responsive Pyridyl(benzamide)-Functionalized NHC Ligand on Ir Complex for Alkylation of Ketones and Secondary Alcohols

A Cp*Ir(III) complex ( 1 ) of a newly designed ligand L¹ featuring a proton-responsive pyridyl(benzamide) appended on N - heterocyclic carbene (NHC) has been synthesized. The molecular structure of 1 reveals a dearomatized form of the ligand. The protonation of 1 with HBF₄ in tetrahydrofuran gives the corresponding aromatized complex [Cp*Ir(L¹H)Cl]BF₄ ( 2 ). Both compounds are characterized spectroscopically and by X-ray crystallography. The protonation of 1 with acid is examined by ¹H NMR and UV-vis spectra. The proton-responsive character of 1 is exploited for catalyzing α-alkylation of ketones and β-alkylation of secondary alcohols using primary alcohols as alkylating agents through hydrogen-borrowing methodology. Compound 1 is an effective catalyst for these reactions and exhibits a superior activity in comparison to a structurally similar iridium complex [Cp*Ir(L²)Cl]PF₆ ( 3 ) lacking a proton-responsive pendant amide moiety. The catalytic alkylation is characterized by a wide substrate scope, low catalyst and base loadings, and a short reaction time. The catalytic efficacy of 1 is also demonstrated for the syntheses of quinoline and lactone derivatives via acceptorless dehydrogenation, and selective alkylation of two steroids, pregnenolone and testosterone. Detailed mechanistic investigations and DFT calculations substantiate the role of the proton-responsive ligand in the hydrogen-borrowing process.     

Base-catalyzed cross coupling of secondary alcohols and aryl-aldehydes with concomitant oxidation of alcohols to ketones: An alternative route for synthesis of the Claisen-Schmidt condensation products

Base-catalyzed C–C cross coupling of secondary alcohols and aryl-aldehydes was achieved, when an alcoholic solution of an aryl-aldehyde was stirred under reflux for 45 h in the presence of a catalytic (20 mol%) amount of K₂CO₃. The consistent formation of α,α′-bis-(benzylidene) alkanones was obtained in moderate to good yields using various secondary alcohols and substituted aryl-aldehydes. Herein, α,α′-bis-(benzylidene)alkanones, which are the classical products of Claisen-Schmidt (cross aldol) condensation, have been synthesized via an alternative strategy using secondary alcohols. Bis-(benzylidene) alkanones are an integral part of various drug regimes and the production of bis-(benzylidene) alkanones without using any precious metal is a major outcome of the present reaction.