Sequential Aldol Condensation-Transition Metal-Catalyzed Addition Reactions of Aldehydes, Methyl Ketones, and Arylboronic Acids

Abstract

Sequential aldol condensation of aldehydes with methyl ketones followed by transition metal-catalyzed addition reactions of arylboronic acids to form β-substituted ketones is described. By using the 1,1′-spirobiindane-7,7′-diol (SPINOL)-based phosphite, an asymmetric version of this type of sequential reaction, with up to 92% ee, was also realized. Our study provided an efficient method to access β-substituted ketones and might lead to the development of other sequential/tandem reactions with transition metal-catalyzed addition reactions as the key step.

Water Compatible Multicomponent Cascade Suzuki/Heck–Aldol, Suzuki–Aldol–Suzuki, and Aldol–Suzuki–Aldol Reactions: An Ecofriendly Paradigm for Multiple CarbonCarbon Bond Formation in One Pot

“…Among various organic transformations in water,2 Suzuki–Miyaura (S–M) cross‐coupling3 and Aldol condensation (AC) reactions4 occupy esteemed positions as both reactions tend to enrich molecular diversity by formation of CC and CC bonds, respectively. However, cascade reactions involving Suzuki–Miyaura cross‐coupling and Aldol condensation reactions in one pot in an aqueous environment for the generation of biarylchalcones (C 6 ‐C 6 ‐CC‐CO‐C 6 ) is an important but still challenging transformation because of oxidative scission of the double bond in the presence of palladium catalysts,5 the dehydroboration of boronic acids with water at elevated temperatures,6 and the formation of β‐arylated ketones as a side product 7…”

“…However, cascade reactions involving Suzuki-Miyaura cross-coupling and Aldol condensation reactions in one pot in an aqueous environment for the generation of biarylchalcones (C 6 -C 6 -C=C-CO-C 6 ) is an important but still challenging transformation because of oxidative scission of the double bond in the presence of palladium catalysts, [5] the dehydroboration of boronic acids with water at elevated temperatures, [6] and the formation of b-arylated ketones as a side product. [7] Biarylchalcones have gained significance in the field of medicinal chemistry because of their anticancer activities [8] (Figure 1). However, their synthesis [8,9] either proceeds through one-pot two-step processes or in water-co-solvent mixtures as the reaction media.…”

“…Recently, the synergy between multicomponent and cascade reactions has emerged as a tool for the generation of multifunctional molecules in an operationally simple manner with the fewest possible steps and high atom economy. [10] Therefore, it would be the icing on the cake if a multicomponent cascade synthesis of biarylchalcones was found that could be carried out solely in an aqueous medium by overcoming the existing issues, [5][6][7][8][9] including the incompatibility of the catalysts with different substrates and their insolubility in water.…”

Kinetic Study of the Aldol Condensation of Isobutyraldehyde Catalyzed by Sodium Hydroxide

“…In connection with the high reactivity of the aldehydes as their specific feature, it is necessary to select the suitable reaction conditions in planning the course of the synthesis in order to reduce the impact of side processes [2]- [4]. The most widely known side reactions, accompanying typical conditions of the Tishchenko reactions include: aldol condensation [5], Tollens reaction [6], Canizzaro reaction [7], oxidation by means of atmospheric air, transesterification [8], hydrolysis of reaction products [9], the Meerwein-Ponndorf-Verley reduction (MPV reduction) [10] [11], the Oppenauer oxidation reaction [12].…”

Tandem Aldol Condensation/Platinacycle‐Catalyzed Addition Reactions of Aldehydes, Methyl Ketones, and Arylboronic Acids

“…In this context, we have recently documented the sequential aldol condensation of aldehydes with methyl ketones followed by Rh(I)-or anionic four-electron donor-based (Type I) palladacycle 1 (Figure 1) 8,9 -catalyzed addition reaction to access β-arylated ketones (Scheme 1). 10,11 We found that with palladacycle 1 or Rh(I)/diene complex as the catalyst, the reaction of aldehydes, methyl ketones and arylboronic acids could be realized in a sequential fashion, 10 but not in a tandem fashion due to the fast palladacycle 1 - or Rh(I)/diene-catalyzed 1,2-addition reaction of arylboronic acids with aldehydes. Because tandem reactions, in which reaction materials are loaded altogether, are operationally more convenient than sequential reactions, it was of interest to us to realize such reactions in a tandem fashion.…”