Transfer Hydrocyanation of α‐ and α,β‐Substituted Styrenes Catalyzed by Boron Lewis Acids

Abstract

As traightforwardg ram-scale preparation of cyclohexa-1,4-diene-based hydrogen cyanide (HCN) surrogates is reported. These are bench-stable but formally release HCN and rearomatizew hen treated with Lewis acids.F or BCl 3 ,t he formation of the isocyanide adduct [(CN)BCl 3 ] À and the corresponding Wheland complex was verified by mass spectrometry.I nt he presence of 1,1-di-and trisubstituted alkenes, transfer of HCN from the surrogate to the C À Cd ouble bond occurs,affording highly substituted nitriles with Markovnikov selectivity.The success of this transfer hydrocyanation depends on the Lewis acid employed;c atalytic amounts of BCl 3 and (C 6 F 5 ) 2 BCl are shown to be effective while B(C 6 F 5 ) 3 and BF 3 ·OEt 2 are not.Nitriles are synthetically highly versatile since the C N functional group is readily converted into amines or various carbonyl compounds directly at the desired oxidation level. On an industrial scale,t ransition-metal-catalyzed hydrocyanation of alkenes using hydrogen cyanide (HCN) is the most prevalent method to access nitriles. [1] Conversely,t he use of gaseous HCN (b.p.2 5.6 8 8C) in academic laboratories is less appealing despite the atom economy associated with its addition across multiple bonds.T he severe toxicity of HCN [2] sparked efforts to identify less volatile surrogates, [3] and acetone cyanohydrin as well as trimethylsilylcyanide (TMSCN) fulfill this role in nickel-catalyzed alkene hydrocyanation. [4][5][6] Another approach is based on cobalt catalysis, and this radical process makes use of solid tosyl cyanide (TsCN) with PhSiH 3 as the source of the hydrogen atom. [7] Morandi and co-workers recently disclosed a reversible transfer hydrocyanation of alkenes catalyzed by nickel (Scheme 1, top). [8,9] Thee quilibrium can be elegantly shifted toward the right by the release of low-boiling isobutylene.Our laboratory introduced irreversible transfer processes catalyzed by B(C 6 F 5 ) 3 where the driving force is the rearomatization of cyclohexa-1,4-dienes substituted with an electrofuge at either saturated carbon atom. [10] Theg eneral principle behind this strategy is that the boron Lewis acid abstracts ah ydride from the other saturated position to generate aWheland intermediate that eventually releases the electrofuge. [11] With alkenes as p-basic donor molecules, transfer hydrosilylation [12] and hydrogenation, [13] as well as the formal transfer of isobutane, [14] were realized. [15] As illustrated for the transfer hydrogenation, the hydrogen atom labeled in italic is transferred as ah ydride to the more substituted carbon atom, and the hydrogen atom labeled in bold assumes the role of the proton (Scheme 1, middle). Knowing that B(C 6 F 5 ) 3 is able to capture isocyanide from activated nitriles, [16] we anticipated that replacement of hydride by cyanide in cyclohexa-1,4-diene-based surrogates could lead to the related transfer hydrocyanation of alkenes (Scheme 1, gray box). We report here the development of such at ransition-metal-free transformation using readily availab...

The Role of Alkali Metal in α‐MnO2 Catalyzed Ammonia‐Selective Catalysis

“…Lewis acid sites can dominate many important homogeneous or heterogeneous catalytic reactions, for example, asymmetric organic synthesis, catalytic polymerization toward macromolecules, and heterogeneous industrial catalytic reactions ,. It is known that the chemical nature of Lewis acid sites are positively charged centers, whether they are nonmetal (for example, boron), metal (Ni 2+ , Ce 3+ ), or atomic clusters (Ni, Au),, which can attract the electrons and then initiate the reactions. Therefore, it is crucial to understand and control the electronic structure of Lew acid sites, which would bring new strategy for better activating the Lewis acid sites.…”

The Cyclohexa‐2,5‐dienyl Group as a Placeholder for Hydrogen: Organocatalytic Michael Addition of an Acetaldehyde Surrogate

“…The outcome is an ion pair composed of a boron ate complex and a Brønsted acidic Wheland intermediate that can either react with itself or with an added reaction partner. By this, alkene hydrofunctionalizations such as transfer hydrocyanation [7a] and hydromethallylation [7b] have been accomplished. We anticipated that a cyclohexa‐2,5‐dienyl unit α to a carbonyl group could be degraded the same way ( 5 → 6 ), hoping that it would also be compatible with an organocatalytic Michael reaction ( 4 → 5 ; Scheme 1, bottom).…”

Ionic Transfer Reactions with Cyclohexadiene-Based Surrogates

“…Using HCN surrogate 42 (Scheme 17), we quickly established that while B(C 6 F 5 ) 3 was able to catalyze the desired alkene hydrocyanation, significant quantities of alkene dimerization product were formed (not shown). 53 Fortunately, switching to BCl 3 led to essentially complete selectivity for the hydrocyanation products at elevated temperatures. Also of critical importance was the use of a p-xylene-based surrogate.…”