A one-pot oxidation/allylation/oxidation sequence for the preparation of β,γ-unsaturated ketones directly from primary alcohols

A one-pot oxidation/allylation/oxidation procedure has been developed for the conversion of primary alcohols into β,γ-unsaturated ketones. The methodology has been applied to a range of alcohols, and in some cases, isomerisation to produce the corresponding α,β-unsaturated ketones has been carried out.     

Ir-catalysed formation of C-F bonds. From allylic alcohols to α-fluoroketones

A novel iridium-catalysed tandem isomerisation/C-F bond formation from allylic alcohols and Selectfluor? to prepare α-fluorinated ketones as single constitutional isomers is reported.     

Solvolyses de derives de spiro[2.3]hexyle-4

Solvolysis and acid catalysed isomerisation of spiro[2.3]hexyl derivatives are versatile synthetic routes to 2-(Δ¹-cyclobutenyl)ethyl alcohols and methylenecyclopentanols. The course of the reactions is discussed.     

Iridium‐Catalyzed Coupling Reaction of Primary Alcohols with 2‐Alkynes Leading to Hydroacylation Products

A novel iridium‐catalyzed intermolecular coupling reaction of primary alcohols or aldehydes with 2‐alkynes was successfully achieved with high regioselectivity to give hydroacylation products such as α,β‐unsaturated ketones in good yields. The mechanistic investigation of the reaction strongly indicated that the coupling proceeds through the initial formation of homoallylic alcohols followed by dehydrogenation to β,γ‐unsatutated ketones and then isomerisation, which leads to the hydroacylation products.     

Studies on montmorillonite K10-microwave assisted isomerisation of Baylis-Hillman adduct. Synthesis of E-trisubstituted alkenes and synthetic application to lignan core structures by vinyl radical cyclization

The isomerisation of acetates from the Baylis-Hillman adducts with Mont.K10 clay-microwave combination furnished E-trisubstituted alkenes in high yield. The simple Baylis-Hillman adducts with trimethyl orthoformate and unsaturated alcohols under clay catalytic condition gave densely functionalised-isomerized products under solvent free condition. Application of the propargyl derivatives thus obtained from the isomerisation of the Baylis-Hillman adducts with propargyl alcohol has been demonstrated in the synthesis of lignan core structures by tri-n-butyltin hydride mediated vinyl radical cyclization.     

Allylic alcohols as synthetic enolate equivalents: isomerisation and tandem reactions catalysed by transition metal complexes

Allylic alcohols can be isomerised into carbonyl compounds by transition metal complexes. In the last few years, catalyst design and development have resulted in highly efficient isomerisations under mild reaction conditions, including enantioselective versions. In addition, the isomerisation of allylic alcohols has been combined with C-C bond forming reactions when electrophiles such as aldehydes or imines were present in the reaction mixture. Also, C-F bonds can be formed when electrophilic fluorinating reagents are used. Thus, allylic alcohols can be treated as latent enol(ate)s. In this article, we highlight the latest developments concerning the isomerisation of allylic alcohols into carbonyl compounds, focusing in particular on tandem isomerisation/C-C or C-heteroatom bond formation processes. Significant attention is given to the mechanistic aspects of the reactions.     

Regio- and stereochemical aspects in the synthesis of homoallylic alcohols from benzoins and their iodocyclisation to 2,3-diphenyltetrahydrofurans

Indium mediated allylation, crotylation and cinnamylation of benzoins and its substituted derivatives in THF-H₂O (2/1) provide a range of homoallylic alcohols. In general, the benzoins undergo allylation and crotylation in a sluggish manner compared to those observed earlier in the case of α-hydroxy aldehydes and are significantly affected by the electronic features of both the benzoin and indium organometallic reagent. The reactions exhibit higher order of diastereoselectivities than those observed for α-hydroxy aldehydes. The cinnamylation though proceeds in a highly diastereoselective manner but is restricted to only benzoin and 4,4′-dichlorobenzoin. The homoallylic alcohols undergo I₂ mediated intramolecular diastereoselective cyclization to provide 2,3-diphenyltetrahydrofuran derivatives. The relative stereochemistries in tetrahydrofurans and homoallylic alcohols have been assigned by coupling constants, NOE experiments and in one case by X-ray crystallography.     

Preparation of Campholenal Analogues: Chirons for the lipophilic moiety of sandalwood-like odorant alcohols

In connection with structure-activity relationship studies, analogues of campholenal ((+)- 4b ), an important building block for sandalwood-like odorants, were prepared. The five-membered-ring analogues 4 were obtained by epoxidation of the corresponding α-pinene derivatives 2 , followed by catalytic ZnBr₂ isomerisation (Scheme 2). The six-membered-ring skeleton was obtained by ozonolysis of α-campholenyl acetate ((?)- 14b ), followed by intramolecular aldol condensation (Scheme 5). ¹³C-NMR assignments are given.     

Highly efficient and versatile acetylation of alcohols catalyzed by cerium(III) triflate

Cerium(III) triflate is a powerful catalyst for the acetylation of alcohols. The reaction works well for a large variety of simple and functionalized alcohols, without isomerisation of chiral centres. Changes of hydroxyl protective groups are possible in a one-pot procedure. The catalyst can be easily recycled.     

Metal oxo complexes as catalysts for the isomerisation of allylic alcohols

The 1,3-allylic rearrangement of allylic alcohols is an important transformation in organic synthesis and various methods for effecting such a transposition have been reported. This short review will focus on the development of transition metal oxo complexes as catalysts for the isomerisation of allylic alcohols. Mechanistic investigations are also discussed.     

Homogeneously catalysed isomerisation of allylic alcohols to carbonyl compounds

Isomerisation of allylic alcohols forms an elegant shortcut to carbonyl compounds in a completely atom-economical process that offers several useful applications in natural-product synthesis and in bulk chemical processes. This review focuses on the heart of isomerisation catalysis: the catalyst. Combinations of transition metals (from Group 4 to 10), ligands and reaction conditions are compared with respect to yield, turnovers, rate and selectivity. A selected number of clever solutions to synthetic problems are highlighted, such as the synthesis of enols and enolates, chiral carbonyl compounds and silyl substituted ketones. Furthermore, a general overview of the mechanisms proposed for the isomerisation of allylic alcohols is given while some catalyst systems are singled out to discuss mechanistic research.     

Enantioselective α-heterofunctionalisation of carbonyl compounds: organocatalysis is the simplest approach

Enantioselective organocatalytic processes have reached maturity in recent years with an impressive number of applications now available. The application of these advantageous methodologies to the construction of chiral α-hetereofunctionalised carbonyl compounds allows us to obtain important chiral building blocks, such as α-amino acids, α-amino alcohols, aziridines, epoxides, 1,2-diols and α-sulfenylated, selenenylated and halogenated carbonyl derivatives. Proline, imidazolidinone derivatives, cinchona alkaloids and their ammonium salts, as well as Brønsted acid derivatives, have been used as chiral catalysts for these purposes. A survey of contributions in this field will be discussed throughout this review.     

Direct formation of esters and amides from carboxylic acids using diethyl chlorophosphate in pyridine

An efficient method involving pyridine activation of the carboxylate-phosphate anhydride pathway is described resulting in a direct synthesis of esters from carboxylic acids and alcohols, as well as in the formation of useful amide and peptide derivatives. The reaction proceeds with retention of configuration with both chiral secondary alcohols and α-amino acid derivatives. Ester and amide products can be isolated directly in high yield due to the water soluble nature of the side products.     

Alternative method for alkylation of arylpolyhalomethanes with trialkylborane in the presence of magnesium

Reduction of benzal halide derivatives and α,α,α,-trichloromethylbenzene by magnesium powder in DMAc affords α-halocarbanions which then react with triethylborane to give alkylated products. After oxidation with H₂O₂-NaOH, secondary or tertiary alcohols are obtained. Under the same conditions, 1,1-diphenylpropane is obtained from α,α-dichlorodiphenylmethane.     

Bi(OTf)3-catalyed One-pot Synthesis of α-Halo-β-amino Ketones and Acyl Aziridines from 3-Aryl Propargyl Alcohols

A Bi(OTf)₃-catalyed reaction of 3-aryl propargyl alcohols with sulfonamide and halogen source was firstly investigated, which provided a facile route for the synthesis of a large variety of α-halo-β-amino ketones. The key intermediates, β-amino ketones, were obtained through tandem Meyer-Schuster rearrangement reaction of propargyl alcohols and intermolecular Michael addition of α, β-unsaturated ketones and sulfonamide. Then the in situ generated α-halo-β-amino ketones underwent the base-promoted intramolecular cyclization to give diverse acyl aziridines in a one-pot fashion. These transformations are reliable on a large scale. The high yields and convenient experimental operations make it a valuable method for the construction of α-halo-β-amino ketones and acyl aziridine derivatives.     

A novel synthesis of cyclic α-amino aldehydes, amino alcohols, and α-amino acid methyl esters from cyclic ketones through sulfinylaziridines

Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from cyclic ketones and chloromethyl p-tolyl sulfoxide in three steps in good yields, with N-lithio arylamines gave sulfinylaziridines in high yields. On treatment with N-lithio aniline or N-lithio p-chloroaniline, the sulfinylaziridines gave α-amino aldehydes in high yields. The α-amino aldehydes were converted to amino alcohols and α-amino acid methyl esters in moderate to good yields. This procedure offers an efficient method for synthesis of cyclic α-quaternary α-amino aldehydes, amino alcohols, and α-amino acid derivatives from cyclic ketones.     

Enantiomeric analysis of chiral compounds using phosphorus acid chlorides

New achiral separating bifunctional reagents, dichlorides of methylphosphonic and O-ethyl-thiophophoric acids, have been used for the quantitative determination of the enantiomeric composition of α-amino acids (alanine, valine, proline), secondary alcohols (2-octanol, 2-pentanol, 1-methoxy-2-propanol) and α-phenylethylamine. The determination of the enantiomeric composition of optically active α-amino acids, secondary alcohols, and amines is based on the transformation of compounds into symmetric diastereometers using organophosphorous achiral bifunctional reagents followed by the determination of the derivatives by gas chromatography with a mass spectral detector.     

Halogen-lithium exchange versus deprotonation: regioselective mono- and dilithiation of aryl benzyl sulfides. A simple approach to α,2-dilithiotoluene equivalents

Halogen-lithium exchange and deprotonation reactions between aryl benzyl sulfides and alkyllithiums were investigated. The resultant mono- and dilithiated intermediates were converted into the corresponding aldehydes and boronic, or carboxylic acids in good yields. It was found that diethyl ether stabilizes the ortho-lithiated compounds toward isomerisation to the benzylic derivatives. The process occurs easily in THF at low temperature and is a facile route to the α,2-dilithiotoluene derivative which can be transformed into a dicarboxylic acid on treatment with CO₂.     

Efficient access to fluorinated homoallylic alcohols through an indium promoted fluoroallylation reaction

Herein, an efficient access to fluorinated homoallylic alcohol is reported. The fluorinated alcohols were obtained in good to excellent yield using indium and halo-fluorinated allylic derivatives. The developed methodology using γ-substituted halo-fluorinated allylic derivatives gave the corresponding α-substituted fluorinated homoallylic alcohol in good yields and good diastereoselectivities up to 86:14.     

Isomerisation of Primary Propargyl Alcohols to Vinyl Ketones Mediated by Hg(OAc)2

Mercuric acetate mediated isomerisation of primary propargyl alcohols to vinyl ketones analagous to Rupe rearrangement is described.

IICT Communication No. 3790