ChemoselectiveO-formyl andO-acyl protection of alkanolamines, phenoxyethanols and alcohols catalyzed by nickel(ii) and copper(ii)-catalysts

Abstract

A crucial chemoselective O-formyl and O-acyl protection of alkanolamines, phenoxyethanols, and alcohols in the presence of amines catalyzed by Ni(ii) and Cu(ii) complexes with 8-hydroxyquinoline in a homogeneous medium is achieved.

Chemoselective Esterification of Natural and Prebiotic 1,2-Amino Alcohol Amphiphiles in Water

“…Previous work has explored the prebiotic relevance of 1,2amino alcohol and its possible role as early lipid precursors. For example, Mullen and Sutherland introduced 1,2-amino alcohols like 2-hydroxydecylamine (10) as prebiotic cationic amphiphiles. 50 Such species may have been prebiotically synthesized by the reaction of hydrogen cyanide and alkyl aldehydes, the latter being established as products of Fischer− Tropsch reactions, followed by the reduction of the resulting cyanohydrins (Figure S14A).…”

“…Our method of synthesis of sphingomyelin analogues involved selective O-acylation of a hydroxy group in the presence of an adjacent free amine. Although chemoselective acylation of alcohols has been demonstrated in the presence of amines in organic solvents under both metal catalysis and organocatalysis, ,,,− such transformations are generally regarded as challenging, particularly in aqueous media. , Therefore, our method may facilitate the development of mild strategies for selective O-acylation of organic molecules, which is of interest in medicinal chemistry and carbohydrate chemistry. ,− Another area where we foresee applications of our methodology is the development of artificial metalloenzymes capable of catalyzing acylation reactions . Finally, exploring metal ion-catalyzed selective high-yielding acylation reactions in aqueous media is important in prebiotic chemistry, particularly in the context of the synthesis of phospholipids and other complex membrane lipids. , Our method of metal ion-directed acylation of 1,2-amino alcohol amphiphiles leads to stable and high-yielding ester formation particularly at slightly acidic pH.…”

“…Metal Ion-Directed Selective O-Acylation of Nonbiological 1,2-Amino Alcohol Amphiphiles a a (A) Fingolimod ( 9). (B) 2-Hydroxydecylamine (10). and intermolecular networks formed by interfacial hydrogen bonding, and small structural differences can have a large impact on these interactions.…”

“…This transformation is a rare example of selective O-acylation in the presence of a more nucleophilic amine. There are a few reports of metal-directed regioselectivity switches between acylation sites (i.e., preference of alcohol over amine) in organic solvents like toluene and diisopropyl ether, often under harsh conditions like high temperature over prolonged periods. − However, to our knowledge, there are no examples of nonenzymatic regioselectivity switches that occur in mild aqueous biochemically relevant conditions. In addition, acyl thioesters are not known to spontaneously react with either amines or alcohols due to their kinetic inertness.…”

Formylation of Propargylic Alcohols with Difluorocarbene

“…The formate group is a prevalent motif in natural products and medicinal molecules, and has certain biological activities and pharmacological properties [1] . For example, Cefamandole nafate is a substance that inhibits the growth or reproduction of bacteria (anti‐bacterial agent), [1a] and Formylated estrone is an inhibitor of human steroid sulfatase [1b] . Meanwhile, formate compounds are a kind of important intermediates in organic synthesis, which are widely used in natural flavoring food ingredients and fragrances fields.…”