Synthesis of pentafluorobenzene-based NHC adducts and their catalytic activity in the microwave-assisted reactions of aldehydes

Microwave-Assisted Synthesis of Heterocyclic Scaffolds

“…Additionally, NHC-catalyzed reactions can give rise to other reactive intermediates such as homoenolates for condensation reactions, such as Michael additions, and enolates for aldol reactions. 80 Papadaki et al reported microwave-assisted hydroxymethylation 164 of numerous aliphatic and aromatic aldehydes 163 (Scheme 38) catalyzed by pentafluorobenzene-based NHCs. The carbenic centers were well protected by the inclusion of the C 6 HF 5 -group, which also made it possible for the active carbene to be released under microwave or normal heating conditions.…”

“…Additionally, NHC-catalyzed reactions can give rise to other reactive intermediates such as homoenolates for condensation reactions, such as Michael additions, and enolates for aldol reactions. 80…”

“…The carbenic centers were well protected by the inclusion of the C 6 HF 5 -group, which also made it possible for the active carbene to be released under microwave or normal heating conditions. 80 A new range of N-heterocyclic carbene ligands 169 (Scheme 39 ) has been synthesized by Varenikov et al 81 the synthesis was based on an imidazo[1,5- a ]pyridine-3-ylidine backbone, which is fused to a chiral oxazoline adjunct. Installing the oxazoline functionality using a microwave-assisted condensation of a cyano-azolium salt 167 with various 2-amino alcohols is a crucial step in the synthesis of these ligands.…”

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.…”

Asymmetric Synthesis of N‐Substituted 1,2‐Amino Alcohols from Simple Aldehydes and Amines by One‐Pot Sequential Enzymatic Hydroxymethylation and Asymmetric Reductive Amination

“…The α-hydroxymethyl ketones in turn can be prepared by chemical methods, [16] such as iodine-promoted direct activation and oxidation of styrenes, [17] hydrolyzation of αhaloketones [18] and hydroxymethylation of aldehydes by Nheterocyclic carbenes (NHCs). [16b, 19] However, the direct hydroxymethylation of aldehydes with formaldehyde via biocatalytic CÀ C bond formation would be a highly valuable approach in terms of atom economy, sustainability and compatibility with biocatalytic reductive amination.…”