Hirofumi Matsunaga

Chiral electrophilic 'glycinal' equivalents. New synthons for optically active α-amino acids and 4-substituted 2-oxazolidinones

Abstract The thermal reaction of 3-[(1 S )-2-alkoxy-1-apocamphanecarbonyl]-2-oxazolones ( 21a-c ) with dialkyl azodicarboxylates ( 9 ) results in exclusive formation of [4 + 2] type cycloadducts ( 22 and 23 ) with moderate levels of diastereofacial selection (up to 72% d.e.). The diastereomers thus obtained were readily purified and subsequent treatment with acidic methanol followed by removal of the auxiliary with LiBH 4 MeOH (1:2) gave optically pure 4-methoxy-5-hydrazino-2-oxazolidinones ( 26 and 27 ), which serve as α-aminoaldehyde templates useful for the synthesis of a wide variety of optically active α-amino acids as well as 4-alkyl and 4-aryl-2-oxazolidinones.

An unusual enhancement of chiral induction by chiral 2-imidazolidinone auxiliaries

Diastereoselectivity which is induced by the use of 2-imidazolidinone auxiliaries is greatly dependent on the N-substituents of the heterocycles, among which the bulky arenesulfonyl group is the moiety of choice. Reactions of this type afford an excellent level of diastereoselection in the methylation of N%-butyryl-2-imidazolidinones via the metal enolates.

Unusual N-acylation of sterically congested trans-4,5-disubstituted 2-imidazolidinones: remarkably facile CC bond formation

Abstract Sterically congested trans -4,5-di- tert -butyl-2-imidazolidinone (DTBIm) and trans -4,5-di-(1-adamantyl)-2-imidazolidinone (DAIm), which are prepared from the parent 1,3-dihydro-2-imidazolone, undergo an unusual N -acylation reaction with acyl chlorides in the presence of organic amines to give the 3-oxoacyl derivatives.

A Bicyclic N-Heterocyclic Carbene as a Bulky but Accessible Ligand: Application to the Copper-Catalyzed Borylations of Aryl Halides

Imidazol-2-ylidene and imidazolin-2-ylidene are frequently employed as the core structures of N-heterocyclic carbene (NHC) ligands, because these have two nitrogen sites adjacent to carbenic carbons. The electronic and steric effects of N-substituents to a bound metal have been aptly studied, and bulky substituents have commonly been introduced on nitrogen(s). However, too much bulkiness can sometimes result in an ineffectiveness of the hindered substrates. In this study, we thoroughly compared our original bicyclic NHC, which has bulky substituents on its noncarbenic carbons, with ubiquitous NHC ligands to probe its steric properties. A well-defined bicyclic NHC-CuCl complex was successfully synthesized and applied to the copper-catalyzed borylations of aryl halides at ambient temperature. A bicyclic NHC-CuCl proved to be a better catalyst than commonly used NHC ligand-Cu complexes, particularly for sterically hindered substrates, which suggested that the bicyclic NHC ligand offered a bulky but accessible environment to the bound copper.

An N-Heterocyclic Carbene-Nickel Half-Sandwich Complex as a Precatalyst for Suzuki–Miyaura Coupling of Aryl/Heteroaryl Halides with Aryl/Heteroarylboronic Acids

A nickel half-sandwich complex supported by our original NHC ligand was developed as a robust precatalyst for Suzuki-Miyaura cross-coupling. The addition of PPh3 was a crucial element in the suppression of side reactions and in accelerating the cross-coupling reaction. By employing the optimal conditions, aryl-aryl, heteroaryl-aryl, and heteroaryl-heteroaryl couplings were achieved.

Stereoselective intramolecular radical addition of polyhaloacyl pendant groups to the 1,3-dihydro-2-imidazolone moiety: the chiral synthesis of threo-diaminocarboxylic acids

Abstract The intramolecular Ru(II)-catalyzed radical addition of trichloroacetyl and 2,2-dichloro-4-hexenoyl pendant groups to a 1,3-dihydro-2-imidazolone moiety provides a perfectly stereocontrolled approach to the preparation of 1,2-diamines which contain contiguous multi-stereocenters. Typical examples for this approach are given by the chiral synthesis of vicinal-diaminocarboxylic acids, which are amino analogs of statine and MeBmt.

The highly enantiocontrolled functionalization of a 2-oxazolone heterocycle by intramolecular radical-based addition. A chiral synthon for 2-amino alcohols which contain three contiguous stereocenters

Abstract The intramolecular Ru(II)-catalyzed radical addition of the 2,2-dichloroacyl pendant group to the 2-oxazolone moiety followed by reductive dechlorination with (TMS)3SiH provides an effective tool for the formation of the chiral 2-amino alcohol synthon in a completely regio- and stereocontrolled manner. The prepared synthon is useful in the preparation of isomers of unusual amino hydroxy acids including the key component of bleomycins.

Acceleration of ruthenium(II)- and rhodium(I)-catalyzed hydrogen-transfer reaction by rare earth metal triflates

Abstract The addition of Yb(OTf) 3 as an additive considerably accelerates the RuCl 2 (PPh 3 ) 3 - and RhCl(PPh 3 ) 3 -catalyzed hydrogen-transfer reduction of both aromatic and aliphatic ketones in which Ru:Yb ratios of 1:2–1:4 are critically important for achieving acceleration.

Diastereoselective [2+3]cycloadditions of nitrones to 2-oxazolone heterocycles

Highly diastereoselective [2 + 3] cycloadditions of N-benzyl- and N-tert-butyl-α-phenylnitrones to 3-(2-substituted 7,7-dimethylbicyclo [2.2.1]heptane-1-carbonyl)-2-oxazolones are described

A study of the strength of a template molecule - A functional monomer interaction that affects the performance of molecularly imprinted polymers and its application to chiral amplification

A novel type of molecularly imprinted polymer (MIP), N-benzoyl-(S)-valine anilide-imprinted polymer (IP-2), was prepared using hydrogen-bonding interactions as a main force in the pre-polymerization step. The performance of the IP-2 was evaluated via batch procedure and compared with a (S)-valine anilide-imprinted polymer (IP-1) that was prepared using an ionic interaction that is stronger than hydrogen bonding. Although both polymers showed a preferential adsorbability for (S)-amino acid derivatives, different performances were observed in terms of adsorbability and enantioselectivity. In addition, the IP-2 was able to recognize the enantiomer of a valine-derived chiral catalyst. This phenomenon was applied to a chiral amplification reaction, and a highly selective asymmetric Mannich-type amination was achieved using the combination of a racemic catalyst and a MIP.