Efficient Synthesis of a-Hydroxyacetophenone via Microwave Irradiation of a-Bromoacetophenone from Acetophenone

One-Pot Enzymatic–Chemical Cascade Route for Synthesizing Aromatic α-Hydroxy Ketones

“…In the present study, efficient and environmentally friendly synthesis of 2-HAP was achieved through introducing a spontaneous chemical reaction after Ct PDC1-catalyzed C–C ligation reaction, where the presence of H + and Mg 2+ in solution promoted the spontaneous reaction. Furthermore, compared with chemical reactions requiring higher temperatures, high pressure, and specific light conditions, ,, this spontaneous chemical reaction does not require external energy to drive the transformation, which involves conversion of 4a into 2-HAP via proton transfer, thereby promoting the concepts of “atom economy” and “green chemistry”. , Furthermore, compared with other enzymatic–chemical cascade reactions involving two or more catalysts, ,,− , this spontaneous chemical reaction does not require an additional catalyst, which addresses the potential mass-transfer problem between the two catalysts.…”

“…The relative molecular mass of 5a and 5b were 136.08 and 151.0124 (Figure S2), respectively, detected by GC−MS and LC−MS. The products were then separated and purified using preparative high-performance liquid chromatography and determined by 1 H and 13 C NMR spectroscopy, which revealed a CH 2 -absorption peak for product 5 rather than a CHabsorption peak for product 4 (Figures S3a and S4a). These results demonstrated that the enzymatic−chemical cascade reaction successfully synthesized 5a and 5b.…”

“…2-HAP can be produced using chemical and biocatalytic methods. The chemical synthesis methods mainly include photocatalytic oxidation of phenethyl alcohol, photocatalytic decarboxylative carbonylation of carboxylic acid, , oxidation of phenylglycol or terminal olefin by metal and nanometal catalysis, , and/or dehalogenation of bromoacetophenone catalyzed by microwave radiation . Unfortunately, chemical methods include disadvantages such as harsh reaction conditions, high-priced substrates and catalysts, and technical challenges (such as catalyst stability and heavy metal recovery).…”

Manipulating Activity and Chemoselectivity of a Benzaldehyde Lyase for Efficient Synthesis of α-Hydroxymethyl Ketones and One-Pot Enantio-Complementary Conversion to 1,2-Diols

“…α-Hydroxymethyl ketones are often encountered in the structure of many bioactive products − and are also routinely used as versatile building blocks for the manufacture of high-value important molecules in organic synthesis, with numerous applications as chiral auxiliaries, chiral ligands, or chiral catalysts for asymmetric synthesis (Scheme A). − Several cascade reactions have been established to obtain useful and high-value chemicals with α-hydroxymethyl ketone as an intermediate. − For example, dihydroxyacetone was an important α-hydroxymethyl ketone in the pathway for cell-free starch, hexoses, or l -alanine synthesis. − Owing to its great importance, the development of efficient methods for the synthesis of α-hydroxymethyl ketones is an important research focus in the pharmaceutical industry. The chemical methods for the preparation of α-hydroxymethyl ketones involve iodine-promoted activation, oxidation, and dioxygenation of alkenes, , substitution of α-haloketones, , oxidation of diols, decarboxylative oxidation of carboxylic acids, , and hydroxymethylation of aldehydes by N -heterocyclic carbenes (NHCs). , Compared to conventional chemical methods that often require high toxic and cost reagents, harsh reaction conditions, and sometimes low isolated yields, biocatalysis has become an attractive approach to prepare α-hydroxymethyl ketones. This includes enzymatic reduction of diketones or oxidation of diols, , transamination of amino alcohols by transaminase, and hydroxymethylation of aldehydes catalyzed by thiamine diphosphate (ThDP)-dependent enzyme (Scheme B). ,− Above all, the direct hydroxymethylation of aldehydes with formaldehyde via biocatalytic C–C bond formation would be a highly valuable approach.…”

“…21−23 Owing to its great importance, the development of efficient methods for the synthesis of α-hydroxymethyl ketones is an important research focus in the pharmaceutical industry. The chemical methods for the preparation of α-hydroxymethyl ketones involve iodinepromoted activation, oxidation, and dioxygenation of alkenes, 24,25 substitution of α-haloketones, 26,27 oxidation of diols, 28 decarboxylative oxidation of carboxylic acids, 29,30 and hydroxymethylation of aldehydes by N-heterocyclic carbenes (NHCs). 4,31 Compared to conventional chemical methods that often require high toxic and cost reagents, harsh reaction conditions, and sometimes low isolated yields, biocatalysis has become an attractive approach to prepare α-hydroxymethyl ketones.…”