Insight into O₂‐Promoted Base‐Catalyzed N‐Alkylation of Amines with Alcohols

Abstract

A highly efficient and practical transition‐metal‐free CsOH/O2 catalyst system was developed for the N‐alkylation of amines with alcohols under argon. This strategy was compatible with many alcohols and exhibits excellent functional group tolerance. More significantly, the selective formation of secondary amines was achieved in excellent yields. The detailed mechanistic study gave a clear understanding of the role of base and oxygen in the catalytic cycle.

Potassium tert‐Butoxide‐Mediated Amine Acyl Exchange Reaction of N,N‐Disubstituted Formamides with Aromatic Carbonyl Derivatives via Sequential CN Bond Cleavage/Formation: an Approach to Aromatic Amides

“…To the best of our knowledge, this base‐facilitated aerobic alcohol oxidation process had also been proposed by Xu et al 28a. and Zhao et al 28b. in their transition metal‐free N ‐alkylation reactions.…”

Base‐Mediated Transition‐Metal‐Free Dehydrative C−C and C−N Bond‐Forming Reactions from Alcohols

“…In this context, Yao and Zhao reported the N ‐alkylation of amines with alcohols catalyzed by the CsOH/O 2 system . The reaction of aniline with benzyl alcohol was examined under a large number of conditions, including various bases (CsOH, KOH, NaOH, LiOH, Ba(OH) 2 , Sr(OH) 2 , KO t ‐Bu, and DBU), solvents (mesitylene, H 2 O, PhCl, dioxane, DCE and DMF), temperatures, and under different atmospheres (Ar, N 2 , air and O 2 ).…”

“…In the MPV mechanism, the hydride has to be transferred to the imine from the alkoxide, in turn, generated by reaction of the alcohol with a base. Several examples report that no reaction occurs without base and that the outcome of the dehydrative N ‐alkylation reactions depends on the employed base. Among the wide variety of bases assessed in the N ‐alkylation reactions, NaOH, KOH or CsOH were alternately found to be the most efficient.…”

Interskriptum

“…N ‐Benzylpyridin‐2‐amine 3 q. 20 Following the general procedure, 3 q was obtained as a white solid. 165 mg (90 %); mp 90–91 °C; IR (KBr) (cm −1 ) 3232; 1 H NMR (400 MHz, CDCl 3 ): δ 4.50 (d, J =5.6 Hz, 2 H), 4.95 (brs, 1 H), 6.36 (dt, J =8.4, 1.2 Hz, 1 H), 6.58 (ddd, J =7.2, 5.2, 1.2 Hz, 1 H), 7.23–7.29 (m, 1 H), 7.30–7.36 (m, 2 H), 7.39 (dd, J =8.8, 7.2, 1.6 Hz, 1 H), 8.09 (ddd, J =5.2, 2.0, 1.2 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ): δ 46.3, 106.8, 113.1, 127.0, 127.2, 127.4, 128.6, 137.5, 139.2, 148.2, 158.6; MS (FAB): m/z (%) 185 [M+H] + .…”