The Synthesis of Medium-Chain-Length β-Hydroxy Esters via the Reformatsky Reaction

Abstract

The synthesis of medium-chain-length β-hydroxy esters in good yield via the Reformatsky reaction is described. This work will be used as the basis for further investigation of hydroxyalkanoate polymers as potential feedstock for biofuel production. Reformatsky reaction, biosynthesis, polyhydroxyalkanoate, biofuel, Pseudomonas putida There has been recent interest in developing alternate sources of biofuels that can be used as a replacement for fossil fuels. One of the most prevalent biofuels is biodiesel produced by the methanolysis of long-chain (C16-C20) fatty acid triacyl glycerides that are the major constituents of plant oils. 1 However, biodiesel production results in several by-products, such as glycerol and free fatty acids, which cannot be used as fuels and are of otherwise low value. It has been recently demonstrated that these waste by-products can be used as feedstock for the bacteria Pseudomonas putida LS46. 2 This strain of P. putida can efficiently convert these by-products into a variety of medium-chain-length polyhydroxyalkanoates (mcl-PHAs -Scheme 1), with chain lengths of 6 to 14 carbons. These bioester polymers can be considered of higher value than the biodiesel waste byproducts. For example, polyhydroxyalkanoate (PHA) has been investigated as a feedstock for biodegradable plastics and other products. 3 Key wordsScheme 1 The production of polyhydroxyalkanoates from glycerol or other feedstock by P. putida LS46We are interested in investigating the chemical conversion of PHA into other value-added products, such as 'dropin' biofuels. For example the methanolysis of PHA results in a 3-hydroxymethyl ester with the chain length, and resulting chemical and physical properties, which is dependent on the chemical composition of the feedstock polymer. We decided to investigate 3-hydroxymethyl and -ethyl esters with a full range of chain lengths to determine the optimal of carbon atoms for downstream conversion to biofuel. However, optimizing growth conditions for P. putida to produce PHA with a specific chain length is time-consuming and expensive. In addition, although the free acids are commercially available their average cost (~$10/mg) requires the development of a more economical synthesis. Therefore, a synthetic methodology was developed that would provide a convenient and economical access to a series of 3-hydroxy esters of the required chain length (C4-C12).We decided to investigate the use of the Reformatsky reaction for this purpose as it is one of the most useful methods for the formation 3-hydroxy esters. 4 The Reformatsky reaction can be carried out in aqueous neutral conditions, in contrast to the alkaline conditions required for aldol condensations or the dry inert conditions required when using Grignard reagents. The Reformatsky reaction has been extended to a large variety of substrates 5 and an asymmetric version has even been developed. 6 It was decided that this reaction would offer an attractive approach to synthesize our desired compounds as a series of aldehyde pr...

Photoredox‐Catalyzed Generation of Tertiary Anions from Primary Amines via a Radical Polar Crossover

“…More specifically, we sought to address the classic problem of selective enolate formation (Scheme 3A). Of course, a solution to this has been to use the Reformatsky approach, wherein an α‐bromo ester in the presence of Zn metal can form a zinc enolate (Scheme 3B) [40–42] . The major drawback of Reformatsky reactions is the necessity for relatively unstable α‐halo carbonyls and stoichiometric amounts of metal.…”

Síntesis de compuestos aza-bicíclicos por ciclación intramolecular de imidas

“…En primer lugar, se estudió la reacción de Reformatsky entre acroleína y bromoacetato de etilo siguiendo un procedimiento previamente descrito por Sorensen y colaboradores. 202 Como resultado de esto, se logró obtener el hidroxiéster III-110 con rendimiento inferior al esperado, y por tal motivo se decidió ensayar la alquilación de acroleína con acetato de etilo, siguiendo también un protocolo reportado. 200,203 En consecuencia, se obtuvo el producto esperado con excelente rendimiento (esquema III-40).…”