Palladium catalyzed intramolecular acylcyanation of alkenes using α-iminonitriles

Abstract

Reported here is a palladium catalyzed intramolecular acylcyanation of alkenes using α-iminonitriles. Through this method, highly functionalized indanones are synthesized in moderate to high yields using Pd(PPh3)4, without need for any additional ligands, and a common Lewis acid (ZnCl2). Additionally, the reaction tolerates substitution at various positions on the aromatic ring including electron donating, and electron withdrawing groups.

Pd‐Catalyzed Suzuki–Miyaura Cross‐Coupling of Arylboronic Acids and α‐Iminonitriles through C–CN Bond Activation

“…), and NaOAc (2 equiv.) Solvent screening revealed that when the polarity of the solvent increased, the amount of by-product 3aa (Scheme 2) also increased; cyclohexane was clearly superior to other solvents (Table 1, entries [10][11][12][13][14]. Compared with other copper sources (Table 1, entries 2-6), Cu(TFA) 2 was optimal for this reaction (TFA = trifluoroacetate).…”

“…[4][5][6][7][8] Despite these significant advances, however, cleavage of the C-CN bond of acylnitriles by transition metals to form acyl-metal intermediates [9] for catalytic cross-coupling reactions with organometallic reagents for the chemoselective formation of ketones is virtually unknown. [11] α-Iminonitriles are quite stable to high temperature and water, and cannot undergo decarbonylation, but they can yield a carbonyl group after hydrolysis upon workup. [11] α-Iminonitriles are quite stable to high temperature and water, and cannot undergo decarbonylation, but they can yield a carbonyl group after hydrolysis upon workup.…”

“…This surprising lack of reports on the C-CN activation of acylnitriles in synthetic chemistry is due to the fact that they have a strong tendency to undergo decarbonylation after activation, [10] and also that acylnitriles decompose easily at high temperatures (>100°C). Seminal work by the Douglas group [11] showed that acylnitriles could be substituted by α-iminonitriles; in this way, they achieved the intramolecular acylcyanation of alkenes (Scheme 1a). These characteristics make them fantastic surrogates for acylnitriles.…”

“…Seminal work by the Douglas group [11] showed that acylnitriles could be substituted by α-iminonitriles; in this way, they achieved the intramolecular acylcyanation of alkenes (Scheme 1a). This reaction would be initiated by oxidative addition of the transition-metal to the C-CN bond [11,14] to generate a unique electrophilic imide-metal intermediate, which could then be trapped by a nucleophile, followed by hydrolysis to form the product (Scheme 1b). [13] However, the reaction, which uses stoichiometric amounts of a Lewis acid, suffers from poor compatibility with functional groups, and CO is a toxic gas that is usually used in excess and under high pressure.…”

“Cut and Sew” Transformations via Transition-Metal-Catalyzed Carbon–Carbon Bond Activation

“…In addition, the carbocyanation reaction also proceeded in an intramolecular fashion, 93b,96a–b,97 where use of chiral ligands provided the cyclization products with high enantioselectivities. 96c,98 Acyl nitriles 99 and α-iminonitriles 100 have also been employed as the coupling partners, leading to more functionalized nitrile products. Importantly, Lewis acids, such as BPh 3 , AlMe 3 and AlMe 2 Cl, were demonstrated in 2007 by Hiyama and Nakao to greatly increase the reactivity of the carbocyanation reactions, 101 presumably through coordination with the cyano group to facilitate the oxidative addition step.…”