One-Pot Sequential Kinetic Profiling of a Highly Reactive Manganese Catalyst for Ketone Hydroboration: Leveraging σ-Bond Metathesis via Alkoxide Exchange Steps

Abstract

A comprehensive experimental and computational mechanistic study of the highly enantioselective hydroboration of ketones catalyzed by a manganese(II) alkyl boxmi pincer complex is reported. The catalyst operates at low catalyst loadings (down to 0.01 mol %) under very mild conditions (typically -40 °C) and facilitates the reduction of both aryl alkyl and dialkyl ketones with excellent selectivity (up to >95%ee). Catalyst activation pathways were investigated, demonstrating that a manganese(II) hydride and a manganese(II) alkoxide species are part of the catalytic cycle and can be generated via σ-bond metathesis of the alkyl precursor with the borane or by alcoholysis. Extensive kinetic experiments based on a "one-pot sequential kinetic profiling" approach under various conditions in combination with kinetic simulations reveal that two catalytic cycles are effective with this earth-abundant base metal catalyst: (i) a minor MnH/borane-mediated insertion cycle, in which the subsequent, product-releasing metathesis step is rate determining ( k = 0.076 s), giving a background reaction, which is zeroth order in substrate concentrations, and (ii) a major MnOR/borane-based alkoxide exchange process, leveraging the high-barrier metathesis via the affiliation to an insertion step. The latter features non-integer reaction orders in both reagents due to a combination of an adduct formation step ( k = 2.12 M s, k = 0.49 s) and a substrate insertion step of comparable rates ( k = 3.74 M s). The kinetic findings are underpinned by high-level density functional theory calculations of the mechanism, control experiments, and kinetic isotope effect/Hammett/Eyring analysis in different concentration regimes. The study highlights the role of a rigorous mechanistic understanding of homogeneous catalytic processes in 3d metals for rational catalyst discovery and optimization.

Manganese-catalyzed hydroboration of carbon dioxide and other challenging carbonyl groups

“…Given the slow rate of the B–H bond cleavage, we currently favor the direct attack. The hydride complex II could carry an alternative catalytic cycle involving a second molecule of pinacolborane, similar to the mechanism deduced from kinetic studies most recently by Gade et al for hydroboration of ketones and aldehydes with a Mn-catalyst that cannot form a Mn=N unit 48 . In case of pre-catalyst 1 , an additional open coordination site would have to be provided, e.g., through loss of CO, to enable such a cycle that would bypass the formation of species I and IIa .…”

“…On basis of the experimental observations and current literature precedent in Manganese catalysis, a tentative mechanism for the activation of the B–H bond and its transfer to the rather inert C=O units using complex 1 can be proposed as exemplified for the hydroboration of carbon dioxide in Fig. 3 48 – 52 . In the presence of base, complex 1 reacts to the actual active species I .…”

First-Row Transition Metal (De)Hydrogenation Catalysis Based On Functional Pincer Ligands

“…208 Iron, cobalt and manganese complexes with this family of ligands were utilized in enantioselective ketone reduction, 209 enantioselective ketone hydrosilylation, 210,211 and enantioselective ketone hydroboration. 212,213 Figure 6. Boxmi and PdmBox ligands.…”

Visual kinetic analysis

“…VTNA has already been used successfully by academic and industrial research groups in metal-catalysed [25][26][27][28][29][30][31][32][33][34][35][36][37][38] and organocatalytic reactions. [39][40][41][42][43]…”