Enantioselective Addition Reaction of Azlactones with Styrene Derivatives Catalyzed by Strong Chiral Brønsted Acids

An enantioselective intermolecular addition reaction of azlactones, as carbon nucleophiles, with styrene derivatives, as simple olefins, was demonstrated using a newly developed chiral Brønsted acid catalyst, namely, F₁₀BINOL‐derived N‐triflyl phosphoramide. Addition products having vicinal tetrasubstituted carbon centers, one of which is an all‐carbon quaternary stereogenic center, were formed in good yields with moderate to high stereoselectivities. Extremely high acidity of the new chiral Brønsted acid was confirmed by its calculated pK_a value based on DFT studies and is the key to accomplishing not only high catalytic activity but also efficient stereocontrol in the intermolecular addition.     

Chiral Phosphoric Acids in Metal–Organic Frameworks with Enhanced Acidity and Tunable Catalytic Selectivity

Chiral phosphoric acids are incorporated into indium‐based metal–organic frameworks (In‐MOFs) by sterically preventing them from coordination. This concept leads to the synthesis of three chiral porous 3D In‐MOFs with different network topologies constructed from three enantiopure 1,1′‐biphenol‐phosphoric acid derived tetracarboxylate linkers. More importantly, all the uncoordinated phosphoric acid groups are periodically aligned within the channels and display significantly enhanced acidity compared to the non‐immobilized acids. This facilitates the Brønsted acid catalysis of asymmetric condensation/amine addition and imine reduction. The enantioselectivities can be tuned (up to >99 % ee) by varying the substituents to achieve a nearly linear correlation with the concentrations of steric bulky groups in the MOFs. DFT calculations suggest that the framework provides a chiral confined microenvironment that dictates both selectivity and reactivity of chiral MOFs.     

Enantioselective Aza‐Ene‐type Reactions of Enamides with Gold Carbenes Generated from α‐Diazoesters

Carbophilic gold carbenes generated from the decomposition of α‐diazoesters show high reactivity towards enamides, leading to an unprecedented aza‐ene‐type reaction. The presence of 0.1 mol % of a chiral Brønsted acid co‐catalyst is sufficient to give synthetically relevant γ‐keto esters in excellent yields and selectivities (up to 99 % yield, 97 % ee ).     

Asymmetric Synthesis of Chiral 1,4‐Enynes through Organocatalytic Alkenylation of Propargyl Alcohols with Trialkenylboroxines

A highly enantioselective synthesis of 1,4‐enynes is described that proceeds through an organocatalytic reaction between propargyl alcohols and trialkenylboroxines. Our strategy relies on acid‐mediated generation of the carbocationic intermediate from propargyl alcohols followed by enantioselective alkenylation with trialkenylboroxines. A range of chiral 1,4‐enynes were obtained in moderate to good yields with high levels of enantioselectivity. Use of a highly acidic chiral N‐triflyl phosphoramide catalyst, which has two distant Lewis basic oxygen atoms, was found to be crucial for both high reactivity and selectivity in the present reaction.     

Chiral Brønsted Acid‐Catalyzed Asymmetric Synthesis of N‐Aryl‐cis‐aziridine Carboxylate Esters

We report a multi‐component asymmetric Brønsted acid‐catalyzed aza‐Darzens reaction which is not limited to specific aromatic or heterocyclic aldehydes. Incorporating alkyl diazoacetates and, important for high ee's, ortho‐tert‐butoxyaniline our optimized reaction (i.e. solvent, temperature and catalyst study) affords excellent yields (61–98 %) and mostly >90 % optically active cis‐aziridines. (+)‐Chloramphenicol was generated in 4 steps from commercial starting materials. A tentative mechanism is outlined.     

Catalytic Enantioselective Synthesis of Mariline A and Related Isoindolinones through a Biomimetic Approach

The catalytic enantioselective synthesis of isoindolinones was achieved through the condensation of 2‐acyl‐benzaldehydes and anilines. In the presence of 1 mol % of a chiral phosphoric acid catalyst, reactions reach completion within 10 min and provide products with up to 98 % ee . Anilines with an ortho t ‐butyl group form atropisomeric products, thereby enabling the simultaneous generation of axial and point chirality from two achiral substrates. This method was applied to the first synthesis of mariline A.     

From Palladium to Brønsted Acid Catalysis: Highly Enantioselective Regiodivergent Addition of Alkoxyallenes to Pyrazolones

A highly enantioselective regiodivergent addition of alkoxyallenes to pyrazolones was developed to afford multiply functionalized alkylated products bearing a quaternary carbon stereocenter in high yields with excellent stereoselectivities. One approach is enabled by palladium catalysis, thus leading to branched allylic pyrazol‐5‐ones under mild reaction conditions. The other is catalyzed by a chiral Brønsted acid to give linear products exclusively. Moreover, the usefulness of this new method was highlighted by converting the allylic products into other interesting multifunctionalized pyrazolone derivatives which would be of great potential for the exploitation of pharmaceutically important molecules.     

Switchable Stereoselectivity in Bromoaminocyclization of Olefins: Using Brønsted Acids of Anionic Chiral Cobalt(III) Complexes

Brønsted acids of anionic chiral Co^III complexes act as bifunctional phase‐transfer catalysts to shuttle the substrates across the solvent interface and control stereoselectivity. The diastereomeric chiral Co^III‐templated Brønsted acids, with the same chiral ligands, enabled a switch in the enantioselective bromoaminocyclization of olefins to afford the two enantiomers of 2‐substituted pyrrolidines with high enantioselectivities (up to 99:1 e.r.).     

Catalytic Enantioselective Methylene C(sp3)−H Amidation of 8‐Alkylquinolines Using a Cp*RhIII/Chiral Carboxylic Acid System

Catalytic enantioselective directed methylene C(sp³)?H amidation reactions of 8‐alkylquinolines using a Cp*Rh^III/chiral carboxylic acid (CCA) hybrid catalytic system are described. A binaphthyl‐based chiral carboxylic acid efficiently differentiates between the enantiotopic methylene C?H bonds, which leads to the formation of C?N bonds with good enantioselectivity.     

Enantioselective C(sp3)–H Amidation of Thioamides Catalyzed by a CobaltIII/Chiral Carboxylic Acid Hybrid System

Recent advances in Cp^xM^III catalysis (M=Co, Rh, Ir) have enabled a variety of enantioselective C(sp²)?H functionalization reactions, but enantioselective C(sp³)?H functionalization is still largely unexplored. We describe an asymmetric C(sp³)?H amidation of thioamides using an achiral Co^III/chiral carboxylic acid hybrid catalytic system, which provides easy and straightforward access to chiral β‐amino thiocarbonyl and β‐amino carbonyl building blocks with a quaternary carbon stereocenter.