A novel reduction reaction for the conversion of aldehydes, ketones and primary, secondary and tertiary alcohols into their corresponding alkanes

A novel one-pot reaction has been developed for the reduction of aldehydes, ketones and primary, secondary and tertiary alcohols into their corresponding alkyl function. This is also the first reported method which can efficiently reduce primary, secondary, or tertiary alcohols, without affecting carbon-carbon double bonds, into their corresponding alkyl function in high yields. The reduction utilises either diethylsilane or n-butylsilane as the reducing agent in the presence of the Lewis acid catalyst tris(pentafluorophenyl)borane.     

An expedient route to p-tert-butylthiacalix[4]arene 1,3-diethers via Mitsunobu reactions

Regioselective distal dialkylation of p-tert-butylthiacalix[4]arene with alcohols was performed under the Mitsunobu protocol using the DEAD/TPP system. The method provides a versatile tool for obtaining 1,3-diethers with different functional groups in the alkyl chains.     

A simple one-pot procedure for the direct conversion of alcohols into alkyl nitriles using TsIm

A convenient and efficient one-pot preparation of nitriles from alcohols using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this method, treatment of alcohols with a mixture of NaCN, TsIm and triethylamine in the presence of catalytic amounts of tetra-n-butylammonium iodide (TBAI) in refluxing DMF furnishes the corresponding alkyl nitriles in good yields. This methodology is highly efficient for various structurally diverse alcohols with selectivity for ROH: 1° > 2° > 3°.     

A simple one-pot procedure for the direct conversion of alcohols into azides using TsIm

A facile and efficient method for one-pot conversion of alcohols into azides using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this method, alcohols are refluxed with a mixture of NaN₃, TsIm and triethylamine in the presence of catalytic amounts of tetra-n-butylammonium iodide (TBAI) in DMF affording the corresponding alkyl azides in good yields. This methodology is highly efficient for various structurally diverse alcohols with selectivity for ROH: 1° > 2° > 3°.     

A simple procedure for the esterification of alcohols with sodium carboxylate salts using 1-tosylimidazole (TsIm)

An efficient and selective method for esterification of alcohols using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this method, alcohols are refluxed with a mixture of RCO₂Na (R: alkyl and aryl), TsIm, and triethylamine in the presence of catalytic amounts of tetra-n-butylammonium iodide (TBAI) in DMF to afford the corresponding esters in good yields. This methodology is highly efficient for various structurally diverse alcohols with selectivity for ROH: 1° > 2° > 3°.     

Copper(I) tert-butoxide-promoted stereospecific alkylation of β-hydroxymethylvinylsilanes with alkyl halides

Stereospecific alkylation of (Z)-β-hydroxymethylvinylsilanes proceeded by treatment with copper(I) tert-butoxide and alkyl halides. Tri- and tetra-substituted allylic alcohols were obtained with complete retention of configuration.     

Domino addition/annulation of δ-alkynylaldehydes and oxygen nucleophiles: a new entry to [1,4]oxazino[4,3-a]indoles

The unusual [1,4]oxazino[4,3-a]indole nucleus was prepared, under mild reaction conditions, by reacting 1-alkynyl-1H-indole-2-carbaldehydes with various alkoxides, generated in situ from the corresponding alkyl, benzyl, allyl and propargyl alcohols.     

Alkylation of ethylenethiourea with alcohols: a convenient synthesis of S-alkyl-isothioureas without toxic alkylating agents

The alkylation of ethylenethiourea with alcohols and aqueous acids (HCl, HBr, and HI) allows the synthesis of the respective S-alkyl-isothioureas in high yield and purity. Consistently high yields (91-98%) were obtained with 56% HI, the yields for 48% HBr (48-93%) and 37% HCl (36-85%) were lower and varied with the type of alcohol. The method is a convenient low-cost alternative to the use of alkyl iodides and an easy access to the S-tert-butyl isothiourea.     

Conversion of tertiary alcohols to tert-alkyl azides by way of quinone-mediated oxidation-reduction condensation using alkyl diphenylphosphinites

A novel method for the preparation of alkyl azides from alcohols by way of oxidation-reduction condensation is described. In this reaction, the sterically-hindered tert-alkyl phosphinites that are prepared from the corresponding alcohols are converted into tert-alkyl azides with almost complete inversion of their stereochemistry: the obtained alkyl azides are then successfully reduced to afford the corresponding amines on treatment with LiAlH₄, thus, a versatile method for the preparation of chiral amines from the corresponding chiral alcohols is established.     

Enzymatic synthesis of alkyl α-2-deoxyglucosides by alkyl alcohol resistant α-glucosidase from Aspergillus niger

Aspergillus niger α-glucosidase (ANGase) was used for an efficient syntheses of alkyl α-d-2-deoxyglucosides (A2DGs) and for regioselectivity studies of alkoxy-hydro additions of d-glucal in the presence of alkyl alcohols. ANGase showed a high stability with respect to the high concentration of alkyl alcohols. The reaction conditions were optimized for pH, temperature, alkyl alcohol concentration, and d-glucal concentration. On the basis of MS and NMR analyses, A2DGs were confirmed to have only an α-2-deoxyglucosidic bond and the two-dimensional NMR (HMBC) spectra showed to be made up of 2-deoxyglucosyl and alkyl moieties.     

Fluorous scavenger for parallel preparation of tertiary sulfonamides leading to secondary amines

Alkylation of secondary sulfonamides by alkyl halides or alcohols (Mitsunobu reaction) is an efficient method for secondary amines preparation. However, its application to parallel chemistry is often difficult due to partial reaction. In this Letter, we propose a fluorous technique to bypass this problem. Thus, o-nitrobenzenesulfonamides were prepared and alkylated in parallel (Fukuyama method) with various alkyl halides or alcohols. Depending on the nature of the alkyl halide or alcohol, this step remained incomplete. A reactive fluorous alkyl iodide was then used to trap the unreacted sulfonamide allowing for a rapid and efficient fluorous solid-phase extraction (FSPE). Some examples of the isolated tertiary sulfonamides were converted in parallel to the corresponding secondary amines with good purity.     

An efficient method for chlorination of alcohols using PPh3/Cl3CCONH2

A new and convenient method for the chlorination of alcohols utilizing PPh₃/Cl₃CCONH₂ is addressed. Various alcohols could smoothly be converted into their corresponding alkyl chlorides in high yield under mild conditions with short reaction times. A mechanism is disclosed with the evidence of inversion of configuration of the analogous alkyl chloride derived from R-(−)-2-octanol.     

Generation of alkyl radicals from alkylsilyl peroxides and their applications to C-N or C-O bond formations

This article describes a novel method for the generation of alkyl radicals from alkylsilyl peroxides and their applications to the Cu-catalyzed mono-N-alkylation of amides or arylamines, and to the O-alkylation of carboxylic acids. The use of alkylsilyl peroxides as alkyl radical sources includes the following synthetic advantages: i) various alkylsilyl peroxides can be readily synthesized from the corresponding alcohols and be stored at bench, and ii) a variety of alkyl radicals can be generated efficiently under mild conditions.     

Rapid identification of enantioselective ketone reductions using targeted microbial libraries

A collection of about 300 microbes was surveyed for the ability to generate chiral secondary alcohols by enantioselective reduction of a series of alkyl aryl ketones. Microbial cultures demonstrating utility in reducing model ketones were arrayed in multi-well plates and used to rapidly identify specific organisms capable of producing chiral alcohols used as intermediates in the synthesis of several drug candidates. Approximately 60 cultures were shown to selectively reduce various ketones providing both the R and S enantiomers of the corresponding alcohols in 92-99% ee with yields up to 95% at 1-4 g/L. An alternative approach to chiral alcohols based on selective microbial oxidation of racemic alcohols is also reported. This study provides a useful reference for generating chiral alcohols by selective microbial bioconversion.     

Acetylation of alcohols with acetic anhydride promoted by N,N,N-trimethylanilinium tribromide

A wide variety of alcohols were reacted with acetic anhydride at room temperature in the presence of a catalytic amount of N,N,N-trimethylanilinium tribromide to produce the corresponding alkyl acetates in good to excellent yields. Following this procedure, acetylation of primary, secondary, and tertiary alcohols has been performed under neutral conditions.     

An efficient and selective tosylation of alcohols with p-toluenesulfonic acid

Silica chloride has been found to be an efficient catalyst for facile tosylation of alcohols directly with p-toluenesulfonic acid in methylene chloride under reflux. The process is associated with selective tosylation of secondary alcohols over primary alcohols.     

Synthesis of alkyl (R)-lactates and alkyl (S,S)-O-lactyllactates by alcoholysis of rac-lactide using Novozym 435

Enzymatic alcoholysis of rac-lactide for kinetic resolution was carried out in organic solvents. Effects of organic solvent, reaction temperature, and alcohol as a nucleophile were also investigated in Novozym 435-catalyzed alcoholysis of rac-lactide. Both alkyl (R)-lactate and alkyl (S,S)-O-lactyllactate were simultaneously obtained in high yields (>45%) and high enantiopurities (>97% ee) through Novozym 435-catalyzed ring-opening of rac-lactide and subsequent enantioselective alcoholysis of the resultant alkyl O-lactyllactate.     

New chiral amino alcohol ligands derived from 1-phenylethylamine for efficient Ru-catalyzed asymmetric transfer hydrogenation

A series of chiral amino alcohols have been prepared from cheap and readily available (S)-1-phenylethylamine through a one-step transformation. The ability of these newly developed amino alcohols as chiral ligands was evaluated in the Ru-catalyzed asymmetric transfer hydrogenation of aromatic alkyl ketones, providing chiral secondary alcohols with good to excellent conversions (71-100%) and moderate to good enantioselectivities (67-95% ee). The results also showed that the structure of these amino alcohols has a significant influence on the conversion and enantioselectivity.     

Selective aerobic oxidation of allylic and benzylic alcohols catalyzed by N-hydroxyindole and copper(I) chloride

In the presence of copper(I) chloride, tert-butyl 1-hydroxy-2-methyl-6-trifluoromethyl-1H-indole-3-carboxylate acted as a catalyst for the chemoselective aerobic oxidation of allylic and benzylic alcohols. A variety of primary and secondary allylic and benzylic alcohols were oxidized into the corresponding α,β-unsaturated carbonyl compounds in good yields without affecting non-allylic alcohols.     

Influence des substituants alkyles sur la force acide ou basique des alcools et des amines

A perturbational treatment of alkyl substitution in alcohols and amines is suggested. The influence of the alkyl substituent is analysed as a sum of two components: a repulsive interaction which is greater in the neutral compounds (alcohols, amines) than in the corresponding negative ions (RO^?, RNH^?); an attractive interaction which is important only in the ions. It is shown furthermore that, even if steric hindrance is not taken into account, solvation enhances the acidities of non-substituted compounds more than those of the substituted ones. The gas phase and solution acidity orders can thus be rationalised. The “inductive effect” of alkyl groups is also discussed. It is pointed out that: (a) an alkyl group may be electron-attracting when attached to an electronegative atom; (b) spreading a net charge does not always stabilize a system. The simple perturbational arguments are supported by ab initio (STO-3G) calculations.