Substrate‐Directed Hydroacylation: Rhodium‐Catalyzed Coupling of Vinylphenols and Nonchelating Aldehydes

Abstract

We report a protocol for the hydroacylation of vinylphenols with aryl, alkenyl, and alkyl aldehydes to form branched products with high selectivity. This cross-coupling yields a-aryl ketones that can be cyclized to benzofurans, and it enables access to eupomatenoid natural products in four steps or less from eugenol. Excellent reactivity and high levels of regioselectivity for the formation of the branched products were observed. We propose that aldehyde decarbonylation is avoided by the use of an anionic directing group on the alkene and a diphosphine ligand with a small bite angle.

Direct Synthesis of Highly Substituted Pyrroles and Dihydropyrroles Using Linear Selective Hydroacylation Reactions

“…Our laboratory has reported the synthesis of highly substituted furanst hrough intermolecular alkyneh ydroacylation, [7] while the Dong group has reportedt he efficient preparation of benzofuran rings using rhodium-catalysed coupling of aldehydes and vinylphenols. [8] In addition, both ourselves [9] andt he Stanley group [10] have described intramolecular conjugatea dditionbased processes to access dihydroquinolones and chromanones, respectively,from hydroacylation adducts.…”

4-Trifluoromethyl-p-quinols as dielectrophiles: three-component, double nucleophilic addition/aromatization reactions

“…4 , entries 8–11) because cyclohexanone is structurally more rigid than either cycloheptanone and acyclic aliphatic ketones, which makes cyclohexanone less reactive towards the C−C bond formation 41 42 43 . The three-component reaction mentioned above provides a convenient access to α-aryl ketones 41 42 44 45 46 47 48 49 having a trifluoromethyl group on the aryl ring ( Fig. 1 ) 24 27 in a single operation 50 51 52 53 54 55 .…”

Metal‐Catalyzed Substrate‐Directed Enantioselective Functionalization of Unactivated Alkenes

“…Historically, this concept has been implemented in directed hydrogenations and has resulted in powerful synthetic methods for the preparation of functionalized chiral products . Extension of this concept to other directed hydrofunctionalizations has led to the development of hydroboration, hydrosilylation and hydroacylation reactions . In contrast, metal‐catalyzed substrate‐ directed enantioselective functionalization of alkenes has been less developed, and notable progress in this area has been achieved recently.…”