Manganese(I)‐Catalyzed β‐Methylation of Alcohols Using Methanol as C₁ Source

Abstract

Highly selective β‐methylation of alcohols was achieved using an earth‐abundant first row transition metal in the air stable molecular manganese complex [Mn(CO)2Br[HN(C2H4PiPr2)2]] 1 ([HN(C2H4PiPr2)2]=MACHO‐iPr). The reaction requires only low loadings of 1 (0.5 mol %), methanolate as base and MeOH as methylation reagent as well as solvent. Various alcohols were β‐methylated with very good selectivity (>99 %) and excellent yield (up to 94 %). Biomass derived aliphatic alcohols and diols were also selectively methylated on the β‐position, opening a pathway to “biohybrid” molecules constructed entirely from non‐fossil carbon. Mechanistic studies indicate that the reaction proceeds through a borrowing hydrogen pathway involving metal–ligand cooperation at the Mn‐pincer complex. This transformation provides a convenient, economical, and environmentally benign pathway for the selective C−C bond formation with potential applications for the preparation of advanced biofuels, fine chemicals, and biologically active molecules

Carbon monoxide and hydrogen (syngas) as a C1-building block for selective catalytic methylation

“…38 The Mn-pincer complex catalyzed de-and re-hydrogenation steps of the organic substrate and intermediates [39][40][41][42][43][44][45][46][47][48][49][50][51][52] and the base mediated aldol condensation are well established and the deuterium scrambling over all three carbon centers is fully consistent with this sequence (Scheme 3a). 22,36 The high degree of deuterium incorporation at the aand b-position in product 4 reects rapid de-and re-hydrogenation at all stages of the catalytic network (Scheme 3a, see the ESI, Section 5.2 and 5.3 †). The manganese-catalyzed generation of formaldehyde from CO/ H 2 is unprecedented, however, and unlocks the overall manifold.…”

On the Mechanism of the Ruthenium‐catalyzed β‐methylation of Alcohols with Methanol

“…For a broad range of primary and secondary alcohols as substrates, the methyl group is introduced selectively in β ‐position providing the branched products in good to very high yields with water as the only byproduct (Scheme ). The synthetic methodology has been transferred and largely extended by the use of Mn(I)‐MACHO complex most recently . In this work we present a mechanistic analysis of this transformation with the original ruthenium catalyst based on experimentally and theoretically compiled data.…”

“…The synthetic methodology has been transferred and largely extended by the use of Mn(I)-MACHO complex most recently. [3] In this work we present a mechanistic analysis of this transformation with the original ruthenium catalyst based on experimentally and theoretically compiled data.From the results of the synthetic studies, we postulated a working hypothesis for the catalytic process exemplified in Scheme 2 for the mono-methylation of 1-phenyl-propane-1-ol 2 a to 1-phenyl-2-methyl-propane-1-ol 3 a. The overall trans-formation involves five individual cycles A-E forming a complex reaction network.…”

“…The synthetic methodology has been transferred and largely extended by the use of Mn(I)-MACHO complex most recently. [3] In this work we present a mechanistic analysis of this transformation with the original ruthenium catalyst based on experimentally and theoretically compiled data.…”

Manganese‐Catalyzed β‐Methylation of Alcohols by Methanol

“…During the revision of our manuscript two related manuscripts appeared. [23] Table 2: Substrate scope for the double methylation at the primary Catom of secondary alcohols. [a] [a] Reaction conditions: 0.1 mol % [Mn-IIIa] (1 mmol), Table 3: Substrate scope for the mono methylation of the secondary Catom.…”