Takahiko Akiyama

Selective Activation of Enantiotopic C(sp3)−Hydrogen by Means of Chiral Phosphoric Acid: Asymmetric Synthesis of Tetrahydroquinoline Derivatives

Chiral phosphoric acid-catalyzed asymmetric C-H functionalization has been achieved. In this process, enantiotopic C(sp(3))-hydrogen is selectively activated by chiral phosphoric acid to afford tetrahydroquinoline derivatives with excellent enantioselectivities (up to 97% ee).

Enantioselective Synthesis of Multisubstituted Biaryl Skeleton by Chiral Phosphoric Acid Catalyzed Desymmetrization/Kinetic Resolution Sequence

Described herein is the enantioselective synthesis of multisubstituted biaryl derivatives by chiral phosphoric acid catalyzed asymmetric bromination. Two asymmetric reactions (desymmetrization and kinetic resolution) proceeded successively to afford chiral biaryls in excellent enantioselectivities (up to 99% ee). Both experimental and computational studies suggested that this excellent selectivity could be achieved via a highly organized hydrogen bond network among a substrate, a catalyst (chiral phosphoric acid), and a brominating reagent (N-bromophthalimide).

Benzothiazoline: Highly Efficient Reducing Agent for the Enantioselective Organocatalytic Transfer Hydrogenation of Ketimines

Benzothiazoline proved to be an efficient reducing agent for the phosphoric acid-catalyzed enantioselective transfer hydrogenation reaction of imines. Corresponding amines were obtained with excellent enantioselectivities.

Expeditious construction of a carbobicyclic skeleton via sp3-C-H functionalization: hydride shift from an aliphatic tertiary position in an internal redox process.

Described herein is the first example of an aliphatic, nonbenzylic hydride shift/cyclization sequence that contains two types of novel sp(3)-C-H functionalization: (1) construction of a tetraline skeleton via [1,5]-hydride shift/cyclization and (2) [1,6]-hydride shift/cyclization to form a five-membered ring (indane derivatives).

Enantioselective aza-Darzens reaction catalyzed by a chiral phosphoric acid.

Aza-Darzens reaction of ethyl diazoacetate with aldimines, derived from phenyl glyoxal, furnished cis-aziridine carboxylates with excellent enantioselectivities by means of a chiral phosphoric acid.

Chiral phosphoric acid catalyzed transfer hydrogenation: facile synthetic access to highly optically active trifluoromethylated amines.

Amines to an end: highly optically active α-CF(3)-functionalized amines can be obtained using metal-free reaction conditions. The method involves the transfer hydrogenation of CF(3)-substituted ketimines catalyzed by 1 and reductive amination of CF(3)-substituted ketones. The synthetic utility of this method was demonstrated by the synthesis of a CF(3) analogue of NPS R-568. PMP=para-methoxyphenyl.

Expeditious Synthesis of Benzopyrans via Lewis Acid-Catalyzed C−H Functionalization: Remarkable Enhancement of Reactivity by an Ortho Substituent

An expeditious construction of a benzopyran skeleton via Lewis acid-catalyzed C-H functionalization was achieved. In this process, a [1,5] hydride shift and 6-endo cyclization successively occurred to give benzopyrans. The presence of substituents ortho to the alkoxy group significantly enhanced the reactivity, affording the desired compounds in excellent chemical yields with short reaction times.

Enantioselective Robinson-Type Annulation Reaction Catalyzed by Chiral Phosphoric Acids†

Lets resolve our differences: Implementation of an enantioselective Michael addition followed by an intramolecular aldol reaction catalyzed by two phosphoric acids has enabled the synthesis of cyclohexenone derivatives with excellent enantioselectivities. Prominent kinetic resolution was observed in the latter reaction. Ar = aromatic group, X = H, halogen, Y = H, Me, halogen.

AlCl3-N,N-dimethylaniline: A new benzyl and allyl ether cleavage reagent.

Abstract Benzyl and allyl ethers have been cleaved readily on treatment with AlCl3 and N,N-dimethylaniline to give parent alcohols in high yields. Comparisons of N,N-dimethylaniline and anisole are also described.

Chiral phosphoric acid-catalyzed oxidative kinetic resolution of indolines based on transfer hydrogenation to imines

The oxidative kinetic resolution of 2-substituted indoline derivatives was achieved by hydrogen transfer to imines by means of a chiral phosphoric acid catalyst. The oxidative kinetic resolution was applicable to racemic alkyl- or aryl-substituted indolines, and the remaining indolines were obtained in good yields with excellent enantioselectivities.