Overcoming Selectivity Issues in Reversible Catalysis: A Transfer Hydrocyanation Exhibiting High Kinetic Control

Abstract

Scheme 2. Experiments to compare relative ease of C-CN oxidative addition/reductive elimination at benzylic and non-benzylic positions. Scheme 3. Development of novel HCN donors for regioselective transfer hydrocyanation. Following further optimization of the reaction conditions, the applicability of this HCN-free, branched-selective transfer hydrocyanation was examined (Scheme 4). A variety of functional groups were well tolerated in the reaction including both electron donating and electron withdrawing moieties. Besides the high branched selectivity of this new reaction, which is complementary to previous HCN transfer protocols, 8d,9a we were also interested to see if it exhibits greater functional group tolerance, given that the current reaction conditions do not require co-catalytic Lewis acid. Indeed, substrates possessing acidic protons (1r-1w) or a Boc-protected amine (1v) were well tolerated. Finally, vinylheteroarenes were also investigated and several common heterocyclic cores (1x-1z) were found to successfully undergo transfer hydrocyanation with high selectivity. Scheme 4. Substrate scope for the regioselective, HCN-free transfer hydrocyanation. a,b a Yields are given for isolated and purified material. Reactions were conducted on a 0.5 mmol scale. b Regioselectivity was determined by 1 H NMR analysis of the crude reaction mixture. c Aldehyde 1k was also isolated in 33% yield.

Transfer C-H Borylation of Alkenes under Rh(I)-Catalysis: In-sight into the Mechanism, Selectivity-Control & Synthetic Capacity

“…However, slow conversion of the high-energy isomer ()-3a to 3a, which is slower than the actual catalytic reaction, indicates that the regioselectivity of the reaction is controlled kinetically, a rather unusual feature in functional group transfer catalysis. 69 Most importantly, because the kinetic control of the selectivity depends on the catalyst, the data suggest the feasibility of accessing different isomers using different catalysts. (1): Fast isomerization of (Z)-3a to (E)-3a indicates that the stereoselectivity of the reaction might be thermodynamically controlled or kinetically controlled at the β-hydride elimination step.…”

New Catalysis Concepts for Molecular Design and Feedstocks Valorization

“…More recently, we have developed a kinetically controlled, yet still reversible variant of the transfer hydrocyanation to obtain branched nitriles. [26] We have also been interested in harnessing the reversibility of the transfer hydrocyanation to construct new catalytic cycles, for example for the cyanation of aryl halides. [27] A central transmetallation between two independently generated Ni II species, from dehydrocyanation of butyronitrile and oxidative addition into the aryl (pseudo)halide, is proposed (Scheme 3b).…”

Iodine Promoted Conversion of Esters to Nitriles and Ketones under Metal-Free Conditions

“…13 2-Phenylpropanenitrile (2q). 25 Yellow oil, yield 44% (34.6 mg). Eluent: Petroleum ether/EtOAc = 30/1.…”