Ramon Mestres

A green look at the aldol reaction

Aldol reactions have been and are widely applied for the preparation of β-hydroxy aldehydes, β-hydroxy ketones or α,β-unsaturated aldehydes or ketones through addition or addition-elimination reactions of aldehydes and ketones. The study of the aldol reaction from the point of view of its greenness must have in mind first of all that a general synthetic method must be based on complete and efficient conversions of well defined selectivity and that greenness is more a term for comparison than an absolute kind of qualification. This comparison, when referred to the aldol reaction, applies here to the diverse modifications of the reaction. Thus, the original poorly selective, but highly atom economic catalytic procedures, have been improved by several authors by introduction of stoichiometric forms of activation in the search for better selectivities. However, the success in these improvements has been accompanied by higher levels of hazard and waste. The study of the greenness of the aldol reaction is completed by a short overview of recent contributions intended to achieve efficient, safe and clean conversions that are susceptible to becoming general green synthetic procedures. Interesting contributions are highlighted for reactions carried out under solvent-less conditions, in water, ionic liquids and supercritical fluids, with activation by microwaves, or with use of heterogeneous catalysis and especially of biocatalysis and biomimetic catalysis. Promising methods based on reduction of unsaturated ketones or on rearrangement of allylic alcohols have also recently been described.

High atomic yield bromine-less benzylic bromination

A two-phase mixture (sodium bromide, aqueous hydrogen peroxide/carbon tetrachloride or chloroform) under visible light provides a simple and convenient system for benzylic bromination of toluenes. A high atomic yield for bromine atoms is attained. Substitution of the chlorinated solvents by other more environmentally benign organic solvents has been attempted and good results are obtained for methyl pivalate.

ALKYLATION OF LITHIUM DIENEDIOLATES OF BUTENOIC ACIDS. REGIOSELECTIVITY EFFECTS OF STRUCTURE AND LEAVING GROUP OF THE ALKYLATING AGENT

Abstract Regioselectivity of alkylation of but-2-enoic acids 1 and 2 by alkyl halides strongly depends on the reactivity of the electrophile. High α selectivity results for saturated alkyl halides, whereas poor α-selectivity is obtained for highly reactive allyl and benzyl halides. For reactive alkylating halides selectivity is partly governed by the ion pairing aggregates of the dienediolates. Lithium bromide and the carboxylate generated in the ongoing reaction cause opposite effects on regioselectivity.

Theoretical model of solvated lithium dienediolate of 2-butenoic acid

Abstract A s-trans dienediolate structure has been theoretically found as a model for the solvated lithium dianion of 2-butenoic acid which is in good agreement with both its chemical reactivity and 13 C NMR spectral data. Semiempirical and ab initio calculations reveal the importance of including a discrete number of the ether solvanting molecules in the calculations of this charged species in solution, and that these ether molecules cannot be substituted by water in the calculations when a conformational equilibrium is possible.

Alkene epoxidations catalysed by Mo(VI) supported on Merrifield's polymer

High conversion and epoxide selectivity from alkenes is achieved with tert-butyl hydroperoxide and a polystyrene-grafted Mo(VI) catalyst, with no noticeable leaching of Mo from the support.

New conditions for the generation of dianions of carboxylic acids

Abstract Lithium carboxylic acid enediolates are generated efficiently using lithium amides prepared from thienyllithium or butyllithium and either diethylamine, piperazine, N,N′-dibenzylethylenediamine, N-benzylpiperazine or 1,3,3-trimethyl-6-azabicyclo[3.2.1]octane, even in catalytic amounts.

LITHIUM ENEDIOLATES AND DIENEDIOLATES OF CARBOXYLIC ACIDS IN SYNTHESIS : ALKYLATION WITH SECONDARY HALIDES

Abstract High yields in the alkylation of dianions of α,β-unsaturated carboxylic acids with secondary halides can be obtained despite elimination reactions occurring. α-Regioselectivity for the alkylation of but-2-enoic acids ( 1–4 ) is seldom obtained. Although double bond stereoselectivity is higher than 99% for γ-alkylated products, stereoselectivity is rather poor for most of the α-alkylated products.

Theoretical model of solvated lithium dienediolates of methyl substituted 2-butenoic acids

Abstract The structures of lithium dienediolates of methyl substituted 2-butenoic acids in ether solution have been studied at PM3 semiempirical level by means of two approaches: the continuum model and the implicit solvation. This study reveals the importance of including three ether molecules for each lithium atom to obtain structures for these species that are in good agreement with the chemical reactivity and 13 C NMR spectral data.

On the mechanism of the addition of organolithium reagents to cinnamic acids

The regioselectivity of the addition of tert-butyllithium to cinnamic acid is subject to reaction conditions and to substituent electronic effects. Significant effects are observed in the presence of several additives including a radical trap such as α-methylstyrene. Competition experiments by addition of the organolithium reagent to mixtures of substituted cinnamic acids show that the relative rates of both conversion of the starting acids and formation of the 1,3-adducts are subject to electronic effects, whereas rates for 1,4-addition are independent of the substituents. These features are in agreement with a polar addition mechanism, but a fast SET equilibrium followed by slow radical combination would be possible as well.

Dienediolates of unsaturated carboxylic acids in synthesis. Aldehydes and ketones from alkyl halides, by ozonolysis of β,γ-unsaturated α-alkyl carboxylic acids. The role of a tertiary amine in the cleavage of ozonides

Abstract A convenient two-step procedure for a two carbon homologative conversion of alkyl halides into aldehydes and methyl ketones by α-alkylation of unsaturated carboxylic acids, followed by ozonolysis is developed and applied to the synthesis of ω-chloro aldehydes. Triethylamine is superior to dimethyl sulfide or triphenylphosphine for cleavage of the ozonides, except when aldol condensation side reactions require use of protic solvents and iodide salts. Cleavage of the ozonides by triethylamine is shown to occur mainly through a reductive process.