Exploring Multistep Continuous‐Flow Hydrosilylation Reactions Catalyzed by Tris(pentafluorophenyl)borane

Abstract

Exploring the combination of continuous-flow processes with the boron Lewis acid catalyzed hydrosilylation of aldehydes and ketones has delivered a robust and generally applicable reaction protocol. Notably this approach permits ready access to high temperatures and pressures and thus allows improved reactivity of substrates that were previously recalcitrant under the traditional approach. Efforts to quench the output from the flow reactor with water showed surprising tolerance leading to the application of continuousflow systems in a multistep imine formation/hydrosilylation processes to generate the corresponding secondary amines from their aldehyde and aniline precursors.

Reverse Polarity Reductive Functionalization of Tertiary Amides via a Dual Iridium-Catalyzed Hydrosilylation and Single Electron Transfer Strategy

“…Our initial investigation focused on sequentially establishing a general set of experimental conditions for both the tertiary amide hydrosilylation and the photocatalytic reductive coupling. For this purpose, the fluorinated N-methyl anilide (1a) was chosen as a model tertiary amide substrate and protected dehydroalanine (DHA) derivative (2) was chosen as a suitably reactive nucleophilic radical acceptor that would ultimately afford medicinally relevant amino acid products (3a) (Scheme 3). 16f, 17 Following exploration of reduction conditions commonly utilized with Vaska's complex, smooth hydrosilylation of the tertiary amide (1a) to the hemiaminal species (1aa) was achieved in under an hour using the addition of 2 mol% of Vaska's complex, and 2 equivalents of TMDS in anhydrous toluene 18 (Scheme 3A, Table 1, entry 2; see Supporting Information for further details).…”

“…1 Traditionally, these valuable structures are accessed through C-N bond forming strategies and numerous protocols have been developed for this purpose. 2 Alternatively, C-C bond formation provides a complementary avenue towards these biologically-relevant architectures. 3 Within the scope of the latter approach, the reductive functionalization of ubiquitous amides is a powerful access point towards decorated α-branched amines.…”

Recent Advances in Water-Tolerance in Frustrated Lewis Pair Chemistry

“…25 Moreover, Melen and co-workers have successfully extended the 1-catalyzed reductive amination process to a continuous-flow process. 26 While borane-catalyzed reductive amination in the presence of aryl-and alkylamines was feasible with silanes, another crucial goal was not achieved: the use of H 2 as the reducing equivalent. This is presumably a kinetic issue as FLP-mediated imine hydrogenation is much slower than imine hydrosilylation, thus with extremely low concentrations of free borane present in these 'wet' reaction mixtures, hydrogenation is effectively retarded.…”

Unlocking the catalytic potential of tris(3,4,5-trifluorophenyl)borane with microwave irradiation

“…Previous work in our research groups has focused on the use of enabling technologies such as flow chemistry to advance the field of main group catalysis. 35 In this work, we seek to develop the scope of main group reactions that can be performed using microwave irradiation as an enabling technology ( Fig. 1).…”