C–H Alkylation of Aldehydes by Merging TBADT Hydrogen Atom Transfer with Nickel Catalysis

Abstract

Catalyst controlled site-selective C−H functionalization is a challenging but powerful tool in organic synthesis. Polarity-matched and sterically controlled hydrogen atom transfer (HAT) provides an excellent opportunity for site-selective functionalization. As such, the dual Ni/photoredox system was successfully employed to generate acyl radicals from aldehydes via selective formyl C−H activation and subsequently cross-coupled to generate ketones, a ubiquitous structural motif present in the vast majority of natural and bioactive molecules. However, only a handful of examples that are constrained to the use of aryl halides are developed. Given the wide availability of amines, we developed a cross-coupling reaction via C−N bond cleavage using the economic nickel and TBADT catalyst for the first time. A range of alkyl and aryl aldehydes were cross-coupled with benzylic and allylic pyridinium salts to afford ketones with a broad spectrum of functional group tolerance. High regioselectivity toward formyl C−H bonds even in the presence of α-methylene carbonyl or αamino/oxy methylene was obtained.

Using High-Power UV-LED to Accelerate a Decatungstate-Anion-Catalyzed Reaction: A Model Study for the Quick Oxidation of Benzyl Alcohol to Benzoic Acid Using Molecular Oxygen

“…Since recent work used a light wavelength of ca. 390 nm for decatungstateanion-catalyzed reactions [29][30][31][32]. We also tested other wavelengths of 385 and 395 nm for the irradiation of decatungstate catalyst and the reactions also proceeded well to give almost the same results compared as for irradiation at 365 nm (Table 1, entry 7 and 8).…”

Nickel/Photo‐Cocatalyzed Acyl C−H Benzylation of Aldehydes with Benzyl Chlorides

“…Control experiments revealed that no desired product was formed in the absence of either Ni-precatalyst (entry 14) or TBADT (entry 15), confirming the synergistic effect of these two catalysts. Moreover, the reaction was nearly or completely shut down when it was carried out without a base or light (entries [16][17].…”

“…[15] Very recently, a similar protocol describing the cross-coupling reaction of aldehydes with benzylic and allylic Katritzky salts via CÀ N bond cleavage was reported by Rasappan and coworkers. [16] As a part of our ongoing studies in this research field, we demonstrate herein the accomplishment of acyl CÀ H benzylation of aldehydes with primary and secondary benzyl chlorides under the cocatalysis of nickel and TBADT (Scheme 1B).…”

“…Subsequently, we successfully implemented the cooperative catalysis of TBADT and nickel in the cross‐coupling reactions of aldehydes with aryl halides, [13] α ‐bromo acetates, [13] N ‐tosyl styrenyl aziridines, [14] as well as allyl acetates [15] . Very recently, a similar protocol describing the cross‐coupling reaction of aldehydes with benzylic and allylic Katritzky salts via C−N bond cleavage was reported by Rasappan and co‐workers [16] . As a part of our ongoing studies in this research field, we demonstrate herein the accomplishment of acyl C−H benzylation of aldehydes with primary and secondary benzyl chlorides under the cocatalysis of nickel and TBADT (Scheme 1B).…”

Nickel/Photo-Cocatalyzed C(sp2)–H Allylation of Aldehydes and Formamides

“…To establish a new strategy for the C­(sp 2 )–H allylation of a formyl moiety, we turned our attention to the cooperative catalysis of nickel and tetrabutylammonium decatungstate (TBADT), which has been applied in cross-coupling reactions involving hydrocarbons or aldehydes. − In our hypothesis, the hydrogen-atom-transfer (HAT) photocatalyst TBADT promotes radical-type umpolung of aldehydes or formamides via homolytic acyl C–H bond cleavage under irradiation, whereas low-valent nickel interacts with electrophilic allyl alcohols or their derivatives to form a π-allylnickel intermediate . The following coupling of these two species generated by distinct catalysts would provide novel access to β,γ-unsaturated ketones or amides (Scheme B).…”