Iron-Catalyzed Methylation Using the Borrowing Hydrogen Approach

Abstract

A general iron-catalyzed methylation has been developed using methanol as a C1 building block. This borrowing hydrogen approach employs a Knolker-type (cyclopentadienone)iron carbonyl complex as catalyst (2 mol %) and exhibits a broad reaction scope. A variety of ketones, indoles, oxindoles, amines, and sulfonamides undergo mono-or dimethylation in excellent isolated yields (>60 examples, 79% average yield).

Recent Catalytic Applications of (Cyclopentadienone)iron Complexes

“…HB methylation of 2‐oxindoles and indoles reported by Morrill (A), indole alkylation reported by Renaud and co‐workers (B), and alkylation of 2‐oxindole reported by Morrill (C) …”

“…HB α‐alkylation of ketones reported by Sortais, Darcel and co‐workers (A), Poater, Renaud and co‐workers (B), and Morrill and co‐workers (C) …”

“…These studies also showed that the formation of catalyst act ‐1f upon ligand dissociation is more favored in the case of the PPh 3 ‐substituted pre‐catalyst 5fa than with other analogs (including 1f ), thus shedding some light on the role of PPh 3 as additive in the above‐discussed work of Sortais and Darcel . Using pre‐catalysts 1a and 1f , Morrill and co‐workers later developed a standard protocol for the methylation and dimethylation of ketones in the presence of K 2 CO 3 , covering a wide range of aromatic ketones (Scheme C).…”

“…Poater and Renaud described a protocol for the methylation and ethylation of aliphatic and aromatic amines promoted the highly active pre‐catalyst 1f . Morrill and co‐workers applied the same protocol employed for ketones – relying on CIC 1a or 1f (see Scheme C) – to the methylation of amines and sulfonamides . In the same paper, 2‐oxindoles and 2‐substituted indoles were also used as nucleophiles for the first time (Scheme A).…”

Selective N‐Monomethylation of Anilines with Methanol Catalyzed by Commercial Pd/C as an Efficient and Reusable Catalyst

“…realized the first homogenously Rh, Ir phosphine complexes‐catalyzed N ‐methylation of amines by methanol in 1981 . Since then, a few homogeneous Ru, Ir, Fe, Mn, and Co complexes have been further developed for the N ‐methylation of amines by methanol. However, these homogeneous catalytic systems cannot be reused, which seriously limited large‐scale industrial applications.…”