Intermolecular -selective Diels-Alder reaction catalysed by dual-functional Brønsted acid: conformational restriction of transition states by hydrogen bonds as the key interaction.

An -selective Diels-Alder (-DA) reaction in which the formed diastereomer is different from that formed in the conventional -selective Diels-Alder (-DA) reaction was developed, which involves a dual-functional Brønsted acid as a catalyst and not only a dienophile (vinylquinoline) but also an acyclic diene (dienylcarbamate) having a sterically less demanding substituent. Factors necessary for achieving the -DA reaction were extracted through an exhaustive computational search of the corresponding transition states, in which the relative orientation of the dienophile and the acyclic diene is firmly defined by hydrogen bonding interactions with a dual-functional Brønsted acid catalyst. It was experimentally verified that the combined use of the dual-functional acid catalyst, such as phosphoric acid, and the conformationally restricted diene (dienylcarbamate), which was realized by the introduction of a substituent at the 2-position of the diene unit, is the key to achieving the -DA reaction.

Computational molecular refinement to enhance enantioselectivity by reinforcing hydrogen bonding interactions in major reaction pathway.

Computational analyses have revealed that the distortion of a catalyst and the substrates and their interactions are key to determining the stability of the transition state. Hence, two strategies "distortion strategy" and "interaction strategy" can be proposed for improving enantiomeric excess in enantioselective reactions. The "distortion strategy" is used as a conventional approach that destabilizes the TS (transition state) of the minor pathway.

One-Pot Synthesis of Enantioenriched β-Amino Secondary Amides via an Enantioselective [4+2] Cycloaddition Reaction of Vinyl Azides with N-Acyl Imines Catalyzed by a Chiral Brønsted Acid.

A catalytic enantioselective synthesis of β-amino secondary amides was achieved using vinyl azides as the enamine-type nucleophile and chiral N-Tf phosphoramide as the chiral Brønsted acid catalyst through a five-step sequential transformation in one pot. The established sequential transformation involves an enantioselective [4+2] cycloaddition reaction of vinyl azides with N-acyl imines as the key stereo-determining step that is efficiently accelerated by a chiral N-Tf phosphoramide catalyst in a highly enantioselective manner in most cases. Further generation of the iminodiazonium ion intermediate through ring opening of the cycloaddition product and subsequent skeletal rearrangement involving Schmidt-type 1,2-aryl group migration followed by recyclization of the resulting nitrilium ion were also initiated by the same acid catalyst.

Chiral Phosphoric Acid Catalyzed Enantioselective Ring Expansion Reaction of 1,3-Dithiane Derivatives: Case Study of the Nature of Ion-Pairing Interaction.

Chiral counterion controlled asymmetric catalysis via an ion-pairing interaction has attracted immense attention in recent years. Despite a number of successful studies, the mechanistic elucidation of the stereocontrolling element in the ion-pairing interaction is rarely conducted and hence its nature is still far from being well understood. Herein we report an in-depth mechanistic case study of a newly developed enantioselective ring expansion reaction of 1,3-dithiane derivatives catalyzed by chiral phosphoric acid (CPA).