Masahisa Nakada

A Non-Heme Iron(III) Complex with Porphyrin-like Properties That Catalyzes Asymmetric Epoxidation

In this report, we describe an iron(III) complex containing a carbazole-based tridentate ligand that catalyzes highly enantioselective asymmetric epoxidation of (E)-alkenes at room temperature. The non-heme iron(III) complex has a five-coordinated trigonal-bipyramidal structure, and its two-electron oxidized state has the similar electronic structure as that of iron porphyrins.

Biomimetic total synthesis of (-)-erinacine E

Biomimetic total synthesis of (−)-erinacine E (1) has been achieved starting from the enantiopure key intermediate, which was prepared via the convergent approach developed by us. The crucial step in this synthesis is an intramolecular aldol reaction driven by the 1,2-migration of a benzoyl group within a compound that was rationally designed to prevent the retro-aldol reaction, thereby successfully providing the strained skeleton of 1. Considering the structure of a putative biosynthetic intermediate, striatal A, the intramolecular aldol reaction driven by the C4‘ acetyl group could be involved in the biosynthesis of 1. This acyl group migratory ring-closing reaction could be applied to the synthesis of other strained molecules.

Total Synthesis of (−)‐FR182877 through Tandem IMDA–IMHDA Reactions and Stereoselective Transition‐Metal‐Mediated Transformations

Intelligent design: The total synthesis of the cytotoxic (-)-FR182877 relies on 1) tandem Diels-Alder reactions to close rings A-D (see scheme), 2) a palladium-mediated 7-exo-trig reaction, and 3) an iridium-mediated isomerization followed by epimerization and stereoselective reduction.

Stereoselective total synthesis of nemorosone

The highly stereoselective total synthesis of nemorosone via a new approach to the bicyclo[3.3.1]nonane-2,4,9-trione core which features intramolecular cyclopropanation of an α-diazo ketone, stereoselective alkylation at the C8 position, and regioselective ring-opening of cyclopropane is described. The total synthesis of nemorosone includes chemo- and stereoselective hydrogenation directed by the internal alkene.

Catalytic asymmetric Nozaki-Hiyama reactions with a tridentate bis(oxazolinyl)carbazole ligand

Nozaki-Hiyama reactions are powerful Cr(II)-mediated C--C bond-forming reactions conducted under mild conditions that show excellent compatibility with various functional groups. Therefore, Nozaki-Hiyama reactions have been utilized for many total syntheses of complex natural products, but at least two equivalents of Cr(II) salt are required to complete the reaction because Cr(II) salt is a one-electron donor. In 1996, however, the quantity of Cr(II) salts required was successfully reduced by a catalytic redox system reported by Fürstner and Shi. Since the report by Fürstner, the catalytic asymmetric Nozaki-Hiyama reactions have attracted attention because they would allow control over enantioselectivity, thereby further enhancing the versatility of Nozaki-Hiyama reactions. In this review, we describe the development of a tridentate bis(oxazolinyl)carbazole ligand for the catalytic asymmetric Nozaki-Hiyama allylation, methallylation, propargylation, and allenylation. Also described are their successful applications to the highly stereoselective construction of the side chain of calcitriol lactone, as well as structure elucidation and the enantioselective first total synthesis of the potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, FR901512 and FR901516.

The first total synthesis of the antitumor macrolide, rhizoxin

Abstract The first total synthesis of the antitumor macrolide, rhizoxin in a highly stereocontrolled manner is described.

The first chemical synthesis of wortmannin by starting from hydrocortisone

Abstract The first chemical synthesis of wortmannin, a potent and specific inhibitor of PI 3-kinases, was achieved by starting from commercially available and optically pure hydrocortisone.

Total syntheses of (-)-scabronines G and A, and (-)-episcabronine A.

Making scab(ronine)s: The total synthesis of (-)-scabronine G features a highly stereoselective oxidative dearomatization/intramolecular inverse-electron-demand Diels-Alder reaction cascade, and the first total synthesis of (-)-scabronine A comprises a highly stereoselective oxa-Michael/protonation/acetalization cascade. The first total synthesis of (-)-episcabronine A includes another highly stereoselective cascade.

Synthetic studies on FR182877: an asymmetric synthesis of the AB ring moiety of FR182877 via a diastereoselective intramolecular Diels-Alder reaction

An asymmetric synthesis of the AB ring moiety of FR182877, possessing seven asymmetric centers, via a diastereoselective IMDA reaction is described.

Catalytic asymmetric [4 + 2] cycloadditions and Hosomi-Sakurai reactions of α-alkylidene β-keto imides.

Highly enantioselective catalytic asymmetric reactions of rationally designed α-alkylidene β-keto imides are described. The [4 + 2] cycloadditions and Hosomi-Sakurai reactions of α-alkylidene β-keto imides proceed with high enantioselectivity and yield. The [4 + 2] cycloadditions of the imides with various dienes afford products bearing an all-carbon quaternary stereogenic center at the ring junction. α-Alkylidene β-keto imides should be useful for the enantioselective total synthesis of natural products and other catalytic asymmetric applications.