Direct Amidation of Alcohols with N‐Substituted Formamides under Transition‐Metal‐Free Conditions

Abstract

Go tandem! The first example of the direct amidation of alcohols with N‐substituted formamides has been developed. A series of tertiary amides, including the challenging N,N‐dimethyl‐substituted amides, were obtained in moderate to good yields under transition‐metal‐free conditions (see scheme). TBHP=tert‐butyl hydroperoxide.

Copper‐Catalyzed Oxidative Coupling of Carboxylic Acids with N,N‐Dialkylformamides: An Approach to the Synthesis of Amides

“…The absence of an amide product with dimethylamine also eliminates the possibility of direct coupling between the acyl and amine radical intermediates (Scheme , b). Depending on the reactants and the catalytic system, various modes for the formation of radicals have been proposed for amide synthesis under oxidative conditions 5b,9,10a,10b. For example, the formation of an amine radical was proposed via tert ‐butyl dimethylcarbamoperoxoate in the direct synthesis of amides from aldehydes and formamides by using Bu 4 NI as the catalyst and TBHP as the oxidant 10a.…”

Cross Dehydrogenative Coupling (CDC) Reactions of N,N‐Disubstituted Formamides, Benzaldehydes and Cycloalkanes

“…Wang et al reported the direct amidation of alcohols with formamides in the presence of an I 2 /TBHP system in combination with NaOH as a base (Scheme ). [30a] The authors highlighted the role of small amounts of water in the reaction: replacement of aq. TBHP with TBHP in decane led to decreases in the yields of the products.…”

“…The same authors reported the amidation of benzylamines with formamides in the presence of I 2 /TBHP under acidic conditions (Scheme ). [30b]…”

Iodine‐Catalyzed Oxidative Coupling Reactions Utilizing CH and XH as Nucleophiles

“…[51] By utilizing I 2 as the catalyst and H 2 O 2 as the oxidant, different substituted acetophenones and tryptamines could be transformed into the corresponding b-carbolines in good to excellent yields [Eq. (34)]. N otably,t his strategyh as also been successfully applied in the total synthesis of other natural products,s uch as fascaplysin and papaverin.…”