Highly efficient synthesis of functionalized α-oxyketones via Weinreb amides homologation with α-oxygenated organolithiums

Abstract

An efficient, chemoselective homologation of Weinreb amides to the corresponding variously substituted α-oxyketones has been developed via the addition of lithiated α-oxygenated species. This one-step, experimentally easy, high yielding protocol is amenable not only for accessing simple α-oxyketones but also for more complex substituted ones ranging from primary and secondary alkyl-type to aromatic ones. Full delivery of the stereochemical information contained in the starting materials is observed through both the employment of enantioenriched Weinreb amides and optically active organolithium species.

A Combination of Pharmacophore and Docking‐based Virtual Screening to Discover new Tyrosinase Inhibitors

“…Moreover the 3D database of compounds from synthetic source was obtained by collecting molecules belonging to different chemical classes (α-,methoxymethylketones, [20] αhalomethylketones, [21] α-cyanomethylketones, [22] α-haloamides, [23] thioamides, [24] spiroepoxyoxindoles, [25] pyrazoles, [26] dithioacetals [18b] designed and synthesized by the Pace group.…”

Sustainable Asymmetric Organolithium Chemistry: Enantio‐ and Chemoselective Acylations through Recycling of Solvent, Sparteine, and Weinreb “Amine”

“…Upon deprotonation of enantiopure amethyl carbamate 18 with sBuLi in CPME, as eries of a-quaternary carbonyl compounds could be prepared in excellent yields and enantiomeric ratios startingf rom the R or S carbamates (sparteinew as not required for deprotonating these chiral starting materials). The trapping with af ormyl Weinreb amide providedt he corresponding a-oxyaldehyde 19,a nd aromatic (20,21), aliphatic (22), or propargylic (23)a nalogues yieldedt he corresponding ketones.…”

“…[19] This is quite astounding because enantiomerically enriched a-substituted ketones constitute privileged frameworks across the chemical sciences. Based on our experienceo fc hemoselective acylations of a-substituted carbanions with Weinreb amides, [20] we devised an enantioand chemoselectivem ethodology to reach aw ide scope of aoxyketones and cyclic a-aminoketonesi nh igh yields, without the need for column chromatography( Scheme 1c). Furthermore,apractical method for the sustainable recovery of sol-…”

Efficient One‐Pot Multifunctionalization of Alkynes en Route to α‐Alkoxyketones, α‐Thioketones, and α‐Thio Thioketals by using an Umpolung Strategy

“…To overcomet he above problems,i nstead of a-halo ketones as the starting materials, Kimpee tal. [28,29] As an important extension of umpolung reactivity,w es upposed that the a-oxygenated ketones or a-thio ketonesc ould be obtained by the reactionofe lectrophilic N-alkenoxypyridinium salts and nucleophilic alcohols or thioalcohols ( Figure 1b). [25] Newman group reported that alco- [a] Prof. Dr.Z.X u, R. Zhai, T. Liang holysis of a-diazoketones under Lewis acidic conditions could afford a-alkoxyketones.…”

“…Aryl ether alkyne substrates also afford fairly good yield of the a-ethanol ketones anda ryl chloride is tolerance (29)(30)(31). Aryl ether alkyne substrates also afford fairly good yield of the a-ethanol ketones anda ryl chloride is tolerance (29)(30)(31).…”