New general synthesis of α-alkoxyketones via α′-alkylation, α-alkylation and α,α′-dialkylation of α-alkoxyketimines

Abstract

a-Methoxy-and a-ethoxyketones, as important intermediates in organic synthesis and flavor compounds in food chemistry, were synthesized by deprotonation of N-(1-alkoxy-2-propylidene)isopropylamine, prepared by condensation of the corresponding a-alkoxyacetone with isopropylamine, and subsequent reaction of the corresponding 1-azaallylic anions with alkyl halides to afford a¢-alkylated, a-alkylated and a,a¢-dialkylated ketimines. Hydrolysis of the imino function led to the desired substituted a-alkoxyketones. The ratio of a-, a¢-, and a,a¢-(di)alkylated compounds depended on the amount of base used and on the nature of the alkylating reagent.

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

“…Other functional groups,s uch as amide, hydroxyl, ester and sulfonyl,a re compatible with the transformationa nd the correspondingp roducts were obtained with good yields (16)(17)(18)(19)(20)(21). Pleasingly,a sr evealed in Ta ble 2, we found ab road range of alkynes possessing various functional groups readilyp articipate in this two-steps one-pot reactionw ith moderate to excellent yields.…”

“…α‐Alkoxyketones, α‐thioketones or α‐thio thioketals not only represents important classes of carbonyl‐containing scaffolds that have wide applications in organic synthesis, but also are common structures found in natural products, drugs, and flavorings . Although many methods have been developed for the synthesis of α‐alkoxyketones, one of the drawbacks is that most of them must use the corresponding ketones as the starting materials which limit the reaction scopes and the substrates are always narrow with poor functional group tolerance .…”

“…[17] Although many methods have been developed for the synthesis of a-alkoxyketones,o ne of the drawbacks is that most of them must use the corresponding ketones as the startingm aterials which limit the reaction scopes and the substratesa re always narrow with poor functional group tolerance. [17] Although many methods have been developed for the synthesis of a-alkoxyketones,o ne of the drawbacks is that most of them must use the corresponding ketones as the startingm aterials which limit the reaction scopes and the substratesa re always narrow with poor functional group tolerance.…”

Gold‐Catalyzed Oxidative Alkyne Functionalization by N−O/S−O/C−O Bond Oxidants

“…[35] α-Alkoxyketones and α-thio ketones are very significant because of their carbonyl-containing scaffolds and wide range of applications in organic synthesis. [36] According to the oxidative alkyne functionalization strategy, the most convenient way to synthesize α-oxygenated or mercaptanated ketones, should be the use of diverse alcohols or mercaptans as nucleophiles directly. Some other methods [36,37,38] have also been established for the synthesis of α-oxygenated ketones but have poor substrate scopes with limited functional group tolerance.…”

“…[36] According to the oxidative alkyne functionalization strategy, the most convenient way to synthesize α-oxygenated or mercaptanated ketones, should be the use of diverse alcohols or mercaptans as nucleophiles directly. Some other methods [36,37,38] have also been established for the synthesis of α-oxygenated ketones but have poor substrate scopes with limited functional group tolerance. However, Zhang established an efficient approach which proceeds through the formation of N-alkenoxypyridinium salt and has wide substrate scopes with super functional group tolerance in a one-pot manner.…”