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A robust and practical difluoroalkylation synthon, α,α‐difluoroenol species, which generated in situ from trifluoromethyl diazo compounds and water in the presence of dirhodium complex, is disclosed. As compared to the presynthesized difluoroenoxysilane and in situ formed difluoroenolate under basic conditions, this difluoroenol intermediate displayed versatile reactivity, resulting in dramatically improved enantioselectivity under mild conditions. As demonstrated in catalytic asymmetric aldol reaction and Mannich reactions with ketones or imines in the presence of chiral organocatalysts, quinine‐derived urea, and chiral phosphoric acid (CPA), respectively, this relay catalysis strategy provides an effective platform for applying asymmetric fluorination chemistry. Moreover, this method features a novel 1,2‐difunctionalization process via installation of a carbonyl motif and an alkyl group on two vicinal carbons, which is a complementary protocol to the metal carbene gem‐difunctionalization reaction. [ABSTRACT FROM AUTHOR]

The catalytic asymmetric construction of all‐carbon quaternary stereocenters has received tremendous interest over the past decades, and numerous efficient protocols have been disclosed based on the formation of one C−C bond between two assembling reactants. However, the use of asymmetric multi‐component reactions that build two C−C bonds on the same carbonic center with concomitant assembly of quaternary stereocenters is rare and remains challenging. Herein, we disclose an enantioselective three‐component reaction of α‐diazo ketones with alkenes and 1,3,5‐triazines under dirhodium/chiral phosphoric acid cooperative catalysis, which leads to a practical and atom‐economic synthesis of poly‐functionalized chiral ketones that bear a α‐quaternary stereocenter in generally good to high yields with excellent enantioselectivities. In comparison to the previous method for the construction of tertiary and quaternary stereocenters via carbene gem‐difunctionalization reactions, this reaction features an unprecedented gem‐dialkylation process via sequential installation of two C−C bonds on the carbene center in one reaction, providing an essential complement to the asymmetric construction of all‐carbon quaternary stereocenters using common and readily available starting materials. [ABSTRACT FROM AUTHOR]

An efficient gold and chiral phosphoric acid cooperatively catalyzed enantioselective oxidative cyclization/Mannich-type addition reaction of homopropargyl amides with nitrones has been developed, which provides chiral pyrrolidin-3-ones in high yields with excellent enantioselectivities under mild conditions. This reaction employed stable and readily available alkynes as non-diazo carbene precursors, which provides a 100% atom economy method with high bond formation efficiency. [ABSTRACT FROM AUTHOR]

An enantioselective three-component reaction of vinyl diazosuccinimdes with alcohols and imines has been realized by a cooperative catalysis of Rh2(OAc)4 and a chiral phosphoric acid, leading to chiral 3,3-disubstituted succinimides in good to high yields with high to excellent enantioselectivity. The generated product with an alkenyl species could be converted to the chiral tricyclic structure under mild conditions. [ABSTRACT FROM AUTHOR]

A synergistic rhodium‐ and Brønsted acid‐ catalyzed reaction of quinone imine ketals with diazo compounds to access multi‐substituted anilines is presented here. This reaction takes place through a process involving C−O bond cleavage, modification of the leaving alcoholic fragment, and selective reassembly of the reactive fragments. Moderate enantioselectivities are achieved when a chiral 1,1'‐bi(2‐naphthol)‐based phosphoric acid is used. [ABSTRACT FROM AUTHOR]

An enantioselective Mannich‐type reaction of 3‐butynol and nitrones is described, which affords dihydrofuran‐3‐ones in good yields and with excellent enantioselectivities. The reaction is initiated by gold‐catalyzed alkyne oxidation and modification of the resulting gold carbene species with a tethered hydroxy group to form enolate species; the reaction terminates with an enantioselective Mannich‐type addition with the assistance of chiral phosphoric acid (CPA) and hydrogen bonding. This novel pattern of alkyne transformation involving chemical bond cleavage, and a fragment modification and reassembly process, provides an atom‐ and step‐economic method, and is the first example of cooperative asymmetric catalysis in gold‐catalyzed alkyne oxidations via an α‐oxo gold carbene route. Golden oldie: A combination of gold(I) and chiral phosphoric acid (CPA) catalyzes a Mannich‐type reaction cooperatively. Asymmetric trapping of a gold enolate intermediate involved in alkyne oxidations occurs via an α‐oxo gold carbene route. Alkyne transformation involves 1) chemical N−O bond cleavage, 2) fragment modification, and 3) reassembly. [ABSTRACT FROM AUTHOR]

A highly enantioselective three-component reaction of a diazoacetophenone, an alcohol, and an imine catalyzed cooperatively by Rh2(OAc)4and BINOL-derived chiral phosphoric acid has been developed for the synthesis of chiral β-amino-α-hydroxyl ketones in good yield with excellent diastereo and enantio selectivity. [ABSTRACT FROM AUTHOR]