Nonbifunctional Outer-Sphere Strategy Achieved Highly Active α-Alkylation of Ketones with Alcohols by N-Heterocyclic Carbene Manganese (NHC-Mn)

Abstract

The unusual nonbifunctional outer-sphere strategy was successfully utilized in developing an easily accessible N-heterocyclic carbene manganese (NHC-Mn) system for highly active α-alkylation of ketones with alcohols. This system was efficient for a wide range of ketones and alcohols under mild reaction conditions, and also for the green synthesis of quinoline derivatives. The direct outer-sphere mechanism and the high activity of the present system demonstrate the potential of nonbifunctional outer-sphere strategy in catalyst design for acceptorless dehydrogenative transformations.

Sustainable and Selective Alkylation of Deactivated Secondary Alcohols to Ketones by Non‐bifunctional Pincer N‐heterocyclic Carbene Manganese

“…All the deuterium‐labeling experimental results show deuterium atoms did not incorporate at the α‐position and mostly distributed in the β‐positions (Scheme b; for more details see Scheme S4). These results imply that a similar mechanism to our previously observed of a direct outer‐sphere mechanism . Subsequently, the progress of model reaction between 1 a and 2 a as a function of time was investigated (Figure S2).…”

“…On the basis of our experimental observations and literature precedents, a plausible reaction pathway is proposed in Scheme . Initially, catalyst C1 reacts with a base to generate an unsaturated reactive species C1‐1 , similar to previous reports .…”

“…Thus, it would be desirable to develop a practical, economical, phosphine‐free and green alkylation process for the formation of α‐alkylated ketones using environmentally friendly first‐row transition metals. Based on our recent progress in practical N‐heterocyclic carbene (NHC) Mn catalysis and the encouraging results reported very recently on the Mn pincer complexes, we envision that non‐bifunctional NHC‐based pincer‐type Mn complex may be a promising catalyst for sustainable coupling between secondary alcohols and primary alcohols, owing to the merit of NHC ligands in easy accessibility, environmental benignancy, stability, and tunable structure . In this context, herein, we report a sustainable and highly selective β‐alkylation of secondary alcohols to give α‐alkylated ketones catalyzed by a practical pincer NHC–Mn catalysis (Scheme c).…”

“…Progress on the α‐alkylation of ketones, esters, or amides using primary alcohols has been recently reported by Beller, Milstein, EI‐Sepelgy, Balaraman, and co‐workers using Mn catalysts (Scheme a). Very recently, we have also reported a phosphine‐free bis ‐NHC Mn promoted α‐alkylation of ketones with primary alcohols to α‐alkylated ketones …”

Tungsten‐Catalyzed Direct N‐Alkylation of Anilines with Alcohols

“…Secondly, the reaction 3 aa* with benzyl alcohol under standard conditions afforded 3 aa in 97 % yield (Scheme 4b), suggesting the N ‐alkylation process follows the BH/HA pathway with imine as the key intermediate. Furthermore, 1 H NMR characterization was performed (Scheme 4c, details see Supporting Information) to detect the in‐situ generated [W−H] species, with 50 mol% pre‐catalyst loading [1c,8m, 14] . Unfortunately, the trap of [W−H] species was not successful probably due to the thermodynamical instability and the high reactivity of the [W−H] species (see DFT results below).…”