α-Methylation of Ketones and Indoles Catalyzed by a Manganese(I) PC_NHCP Pincer Complex with Methanol as a C₁ Source

Abstract

Acceptorless alcohol dehydrogenation is a powerful reaction in sustainable synthesis. When combined in a tandem reaction with dehydrogenative coupling or hydrogen borrowing, acceptorless dehydrogenation can be used for the environmentally benign construction of C−C, C−N, and C−O bonds. While many of these reactions rely on using precious metals, in the past decade the use of earth-abundant metals has become more prevalent. If a green and renewable feedstock could be introduced as well, the sustainability of the acceptorless dehydrogenation could further be increased. Methanol would be such a substrate and could serve as a renewable C1 source when used for the methylation of a wide variety of substrates. Herein, we report the efficient manganesecatalyzed α-methylation of ketones and indoles. The manganese catalyst is based on a PC NHC P pincer platform containing a rare central carbene donor. The reaction supports a diverse set of functional groups, occurs at moderate temperatures (110 °C), and provides the corresponding methylated ketones and indoles in excellent yields. In contrast to previously reported mechanisms, the herein reported mechanism does not depend on metal−ligand cooperativity but rather proceeds via (i) a metal-based mechanism featuring a manganese hydride or (ii) via a ligand-centered mechanism where a manganese-carbonyl acts as catalytic center, depending on the used additive.

Structurally Well-Defined PC(sp3)P Osmium Pincer Catalysts for Methylation of Alcohols, Indoles, Phenols, and Sulfonamides Using Methanol as a C1 Source

“…To start with, 3 was tested as a precatalyst for the β-methylation of alcohols (Scheme ). This one-pot, three-step (i.e., sequential target alcohol/methanol dehydrogenation, cross-aldol condensation, and rehydrogenation) transformation is now well-established to be performed by both late transition metal and earth-abundant metal-based complexes. Although this reaction requires heating due to the key methanol dehydrogenation step (Δ H for methanol is +84 kJ mol –1 ), the average reaction conditions for this method rely on very high reaction temperature (often above 150 °C) even under high catalyst loading.…”

Zn(II)‐Stabilized Azo‐Anion Radical Catalyzed Sustainable C−C Bond Formation: Regioselective Alkylation of Fluorene, Oxindole, and Indoles

“…The reaction did not proceed well without an inorganic base and catalyst (Table 1, entries 13, 14). Commercially available Zn(II)-salts such as ZnCl 2 and Zn(ClO 4 ) 2 were ineffective (Table 1, entries 22,23).…”

Chemoselective Hydrogenation of α,β-Unsaturated Ketones Catalyzed by a Manganese(I) Hydride Complex

“…19 Our mechanistic studies indicated that initial hydride transfer from a Mn(I)-hydride complex, is responsible for the hydrogenation of the in situ formed α,βunsaturated ketone. 19 Inspired by the reactivity of the [(PC NHC P)Mn(CO) 2 H] complex (1), we envisioned that α,β-unsaturated ketones could, perhaps, also be directly hydrogenated with H 2 in a chemoselective manner. Here we report the chemoselective 1,4-reduction of α,β-unsaturated ketones under ambient pressures of hydrogen (mostly 1−2 bar H 2 ) without the need for any additional additives (Figure 1B).…”