Boron-Catalyzed Carboxylic Acid-Selective Aldol Reaction with Trifluoromethyl Ketones

Abstract

SummaryA catalytic carboxylic acid-selective aldol reaction with trifluoromethyl ketones was developed. Reversible and selective covalent bond formation between a boron catalyst and a carboxylic acid is key to realizing the unprecedented catalytic aldol reaction of simple carboxylic acids. The reaction proceeded chemoselectively at the α-position of carboxylic acid even in the presence of ketone, ester, or amide functional groups in the donor substrates. The chemoselectivity is beneficial for late-stage derivatizations of biologically relevant compounds, as demonstrated by the conversion of indomethacin and triacetylcholic acid.

Chemo- and Enantioselective Pd/B Hybrid Catalysis for the Construction of Acyclic Quaternary Carbons: Migratory Allylation of O-Allyl Esters to α-C-Allyl Carboxylic Acids

“…The boron source also affected the reaction (entries 10 and 11). A borane–THF complex (BH 3 ·THF), which was the best catalyst precursor in Mannich and aldol reactions using carboxylic acids as pronucleophiles, was totally ineffective (entry 10, 0% yield). This was probably because boron carboxylate could not be formed from the carboxylate generated through palladium-catalyzed ionization of 1a .…”

Siloxy Esters as Traceless Activators of Carboxylic Acids: Boron‐Catalyzed Chemoselective Asymmetric Aldol Reaction**

“…We began optimization of the reaction between benzaldehyde (3a)a nd propionic acid (4a)u sing ac hiral boron catalyst generated from either BH 3 •SMe 2 or (AcO) 4 B 2 Owith ligand L1 [6,13,17] in toluene (Table 1). In the absence of additives,t he yield of product 5aa was dependent on the loading amount of the boron catalyst (entries 1a nd 2).…”

“…[10][11][12] Themost critical bottleneck lies in the high oxophilicity of the catalysts,r equiring as toichiometric boron mediator to promote aldol reactions,a nd thus, hampering the development of ac atalytic asymmetric variant. [13] Kotani and Nakajima recently reported the first catalytic asymmetric aldol reaction of carboxylic acids (Scheme 1d). [14] Their method employed chiral Lewis base activation of bis(trichlorosilyl)enediolates,p repared from carboxylic acids through treatment with tetrachlorosilane and as terically hindered amine base.H owever,h igh Lewis acidities of tetrachlorosilane and trichlorosilyl group raise potential challenges in practical applicability to complex substrates bearing multiple sensitive functional groups.…”

Theoretical investigation of Prolyl‐Histidine‐catalyzed intermolecular aldol reaction

“…[1] It has many applications in chemistry, pharmacy, chemical engineering, biology, and so forth. [2][3][4][5][6][7][8][9][10][11][12][13][14] A variety of catalysts for aldol reactions, including enzymes antibodies and small molecules, have been developed in the past decades. [15][16][17][18][19] The research of asymmetric synthesis reactions catalyzed by small organic molecules such as amino acids and peptides has become a hot topic.…”