Trio Catalysis Merging Enamine,Brønsted Acid,and Metal Lewis Acid Catalysis: Asymmetric Three‐Component Aza‐Diels–Alder Reaction of Substituted Cinnamaldehydes,Cyclic Ketones,and Arylamines

A trio catalyst system, composed of arylamine, BINOL‐derived phosphoric acid, and Y(OTf)₃, enables the combination of enamine catalysis with both hard metal Lewis acid catalysis and Brønsted acid catalysis for the first time. Using this catalyst system, a three‐component aza‐Diels–Alder reaction of substituted cinnamaldehyde, cyclic ketone, and arylamine is carried out with high chemo‐ and enantioselectivity, affording a series of optically active 1,4‐dihydropyridine (DHP) derivatives are obtained in 91–99 % ee and 59–84 % yield. DHPs bearing a chiral quaternary carbon center are also obtained with good enantioselectivity and moderate yield (three examples). Preliminary mechanistic investigations have also been conducted.     

Enantioselective Dearomatization of Naphthol Derivatives with Allylic Alcohols by Cooperative Iridium and Brønsted Acid Catalysis

The combination of a transition‐metal catalyst and organocatalyst was designed to achieve a highly enantioselective system for the allylic dearomatization reaction of naphthols with racemic secondary allylic alcohols. The desired β‐naphthalenones, bearing an all‐carbon quaternary center, were obtained in good yields with high chemo‐ and enantioselectivities. The cooperative catalytic system, involving a chiral iridium complex and phosphoric acid, provided measurable improvements in yields, and chemo‐ and enantioselectivities relative to single‐catalyst systems. Control experiments indicated that the chiral iridium complex functions as a key species in the control of the absolute configuration, thus enabling the formation of both β‐naphthalenone enantiomers by simply employing opposite enantiomeric ligands.     

Enantio‐ and Diastereoselective Access to Distant Stereocenters Embedded within Tetrahydroxanthenes: Utilizing ortho‐Quinone Methides as Reactive Intermediates in Asymmetric Brønsted Acid Catalysis

A protocol for the highly enantioselective synthesis of 9‐substituted tetrahydroxanthenones by means of asymmetric Brønsted acid catalysis has been developed. A chiral binol‐based N‐triflyphosphoramide was found to promote the in situ generation of ortho‐quinone methides and their subsequent reaction with 1,3‐cyclohexanedione to provide the desired products with excellent enantioselectivities. In addition, a highly enantio‐ and diastereoselective Brønsted acid catalyzed desymmetrization of 5‐monosubstituted 1,3‐dicarbonyl substrates with ortho‐quinone methides gives rise to valuable tetrahydroxanthenes containing two distant stereocenters.     

Synthesis of Pyrrolidine Derivatives by a Platinum/Brønsted Acid Relay Catalytic Cascade Reaction

A new catalytic reaction for the synthesis of pyrrolidine derivatives is presented. The method implies the coupling of N‐Boc‐protected alkynamine derivatives and appropriate alkenes or alkynes in a process catalysed by a platinum/triflic acid catalytic binary system. This reaction is believed to proceed through a cascade process implying an initial platinum‐catalysed cycloisomerization of the alkynamine derivative followed by a triflic acid promoted nucleophilic addition of the alkene or alkyne and trapping of the cationic species formed by the Boc group. Not only simple alkenes and alkynes were used in this reaction but also allyltrimethylsilane and propargyltrimethylsilane. Particularly, when allyltrimethylsilane is used as the alkene counterpart interesting bicyclic compounds containing a trimethylsilane group are obtained. However, when propargyltrimethylsilane is used in the presence of water we observed the formation of a related bicyclic compound lacking the trimethylsilane group and containing an exocyclic carbon?carbon bond.     

One-Pot Tandem Michael Addition/Enantioselective Conia-Ene Cyclization Mediated by Chiral Iron(III)/Silver(I) Cooperative Catalysis

The first one-pot tandem Michael addition/enantioselective Conia-ene cyclization of N-protected prop-2-yn-1-amines with 2-methylene-3-oxoalkanoates promoted by chiral iron(III)/silver(I) cooperative catalysts has been developed. Alkyl 4-methylenepyrrolidine-3-acyl-3-carboxylates, which can be transformed into β-proline derivatives, are obtained in high yield with high enantioselectivity.     

One‐Pot Tandem Michael Addition/Enantioselective Conia‐Ene Cyclization Mediated by Chiral Iron(III)/Silver(I) Cooperative Catalysis

The first one‐pot tandem Michael addition/enantioselective Conia‐ene cyclization of N‐protected prop‐2‐yn‐1‐amines with 2‐methylene‐3‐oxoalkanoates promoted by chiral iron(III)/silver(I) cooperative catalysts has been developed. Alkyl 4‐methylenepyrrolidine‐3‐acyl‐3‐carboxylates, which can be transformed into β‐proline derivatives, are obtained in high yield with high enantioselectivity.     

Catalytic Asymmetric Cycloaddition of In Situ‐Generated ortho‐Quinone Methides and Azlactones by a Triple Brønsted Acid Activation Strategy

A convergent and highly stereoselective [4+2] cycloaddition of in situ‐generated ortho‐Quinone methides (o‐QMs) and azlactone enols has been successfully developed through a triple Brønsted acid catalysis strategy. This protocol provides an efficient and mild access to various densely functionalized dihydrocoumarins bearing adjacent quaternary and tertiary stereogenic centers in high yields with excellent diastereo‐ and enantioselectivity.     

Cooperative Catalysis: Combining an Achiral Metal Catalyst with a Chiral Brønsted Acid Enables Highly Enantioselective Hydrogenation of Imines

Asymmetric hydrogenation of imines leads directly to chiral amines, one of the most important structural units in chemical products, from pharmaceuticals to materials. However, highly effective catalysts are rare. This article reveals that combining an achiral pentamethylcyclopentadienyl (Cp*)–iridium complex with a chiral phosphoric acid affords a catalyst that allows for highly enantioselective hydrogenation of imines derived from aryl ketones, as well as those derived from aliphatic ones, with ee values varying from 81 to 98 %. A range of achiral iridium complexes containing diamine ligands were examined, for which the ligands were shown to have a profound effect on the reaction rate, enantioselectivity and catalyst deactivation. The chiral phosphoric acid is no less important, inducing enantioselection in the hydrogenation. The induction occurs, however, at the expense of the reaction rate.     

Direct Carbohydroxylation of Arylalkenes with Allylic Alcohols: Cooperative Catalysis of Copper,Silver, and a Brønsted Acid

The cooperative catalysis of copper, silver, and Brønsted acid is presented as a new strategy for olefin functionalization. The catalytic direct carbohydroxylation of arylalkenes with allylic alcohols provided a straightforward and efficient approach for preparing 4,5‐unsaturated alcohols. Synthetically useful functional groups, such as Cl, Br, carbonyl, and chloromethyl, remained intact during the functionalization reaction.     

Competitive Silyl–Prins Cyclization versus Tandem Sakurai–Prins Cyclization: An Interesting Substitution Effect

Two different mechanism pathways are observed for the reaction of allylsilyl alcohols 1 and aldehydes in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf). In the case of allylsilyl alcohols without allylic substituents, the reaction gives dioxaspirodecanes, which are the products of a tandem Sakurai–Prins cyclization. In contrast, allylsilyl alcohols with an allylic substituent (R²≠H) selectively provide oxepanes, thus corresponding to a direct silyl–Prins cyclization. Both types of product are obtained with excellent stereoselectivity. Theoretical studies have been performed to obtain some rationalization for the observed stereoselectivity.     

A Brønsted Acid Catalyzed Redox Arylation

A Brønsted acid catalyzed redox arylation of ynamides that employs aryl sulfoxides as the arylating agents is reported. This metal‐free transformation proceeds at room temperature and efficiently affords α‐arylated oxazolidinones in a redox‐neutral, atom‐economic fashion.