Miyuki Ishizaki

Efficient ligands, chiral 2-[2,2-dimethyl-1-(2-pyridyl)propoxy]-1,1-diarylethanols for highly enantioselective addition of alkynylzinc reagents to various aldehydes

Abstract Formation of optically active secondary alkynyl alcohols ( 3 ) (up to 95% e.e.) by the catalysed asymmetric addition of alkynylzinc reagents to aromatic and aliphatic aldehydes in the presence of the tridentate title ligands ( 1a-c ) is described. Interestingly, enantioselectivity in the reaction was proved to be remarkably dependent on the structures of alkynylzinc reagents.

Catalysed asymmetric reaction of aldehydes with dialkylzinc in the presence of chiral pyridyl alcohols as ligands

Abstract The synthesis of homochiral pyridyl alcohols (1,2,3a-c) and a catalytic asymmetric addition of dialkylzinc to various aldehydes using 1-3 as ligands are described. Although the reaction of benzaldehyde with Et2Zn in the presence of (S)-1 and (R,R)-2 gave (S)- and (R)-1-phenyl-1-propanol, respectively, in moderate enantiomeric excess (e.e.), tridentate ligands (3a-c) accelerated the reaction to produce the corresponding alcohols in high e.e. Particularly, (S)-3b was found to be the most efficient catalyst, for which asymmetric reactions of various aldehydes with dialkylzinc gave the corresponding alcohols in good to high e.es. (up to 95% e.e.).

Unprecedented Cesium and Potassium Fluorides Catalyzed Trialkylsilylation and Tributylstannylation of Terminal Alkynes with Trifluoromethyl-Trialkylsilanes and -Tributylstannane

Abstract Cesium and potassium fluorides promoted trialkylsilylation and tributylstannylation of terminal alkynes with trifluoromethyl-trialkylsilanes and -tributylstannane were found to give 1-silyl- and 1-tributylatannyl-alkynes in high yield. The present reactions are applicable to 1-alkynes having a wide range of functional groups such as acetal, iodo, silyl, amino, amido and carbonyl (except for aldehyde) groups.

Investigation of the synthesis of angular tricyclic compounds by intramolecular Pauson–Khand reaction of exo- and endo-cyclic enynes

Abstract Intramolecular Pauson–Khand reaction of various alkynyl exo -alkylidene-cyclohexanes and -pentane gives angular type 6–5–5 and 5–5–5 tricyclic compounds in good to high yield. The present reaction also offers convenient construction of two contiguous quaternary centers, which could not be synthesized from alkynyl endo -cycloolefins. Scope and limitation of the present reaction of various exo - and endo -cyclic enynes are also described.

A first total synthesis of montanine-type amaryllidaceae alkaloids, (±)-coccinine, (±)-montanine, and (±)-pancracine

Abstract Montanine-type Amaryllidaceae alkaloids, (±)-coccinine ( 1 ), (±)-montanine ( 2 ), and (±)-pancracine ( 3 ) were synthesized starting from (±)-1,2- cis -2-(3,4-methylenedioxybenzoyl)cyclohex-4-enecarboxylic acid ( 6 ) via (±)-2,3- cis -3-benzyloxy-2-hyroxy-4a,11a- cis -11,11a-syn-5,11-methano-8,9-methylenedioxymorphanthridine ( 7 ) as a key compound.

Potential intermediate, (±)-di-o-acetyl-3α-phenylselanyl-3,3a-dihydro-B-nor-6,7a-secolycorin-5-one for synthesis of the Amaryllidaceae alkaloid lycorine: formal and total syntheses of (±)-lycorine

Formal and total syntheses of the Amaryllidaceae alkaloid, (±)-lycorine 1, were achieved by new synthetic routes via(±)-di-o-acetyl-3α-phenylselanyl-3,3a-dihydro-B-nor-6,7a-secolycorin-5-one 32. Namely, stereoselective intramolecular Diels–Alder reaction of triene ester 5 afforded, in good yield, the cis-lactone 6, which was converted into β(stereochemical)-hydroxy-γ-lactam 23. Oxidation of silyl ether 24 with m-chloroperbenzoic acid gave only β-(tert-butyldimethylsiloxy)-α-epoxide 25, the stereostructure of which was determined by its X-ray crystallographic analysis. Payne rearrangement of compound 25 and successive acetylation furnished α(stereochemical)-acetoxy-β(stereochemical)-epoxy γ-lactam 29, which was transformed into (±)-lycorine 1 by construction of the B ring. Formal total synthesis of(±)-lycorine 1 is also described.

Scope and limitation of intramolecular Pauson–Khand reaction of fluorine-containing enynes

Abstract Intramolecular Pauson–Khand reaction of various fluorine-containing enynes was investigated under various conditions. The reaction of the substrates, which have fluorine atom(s) or fluorine-containing group(s) attached to alkenyl moiety, gave the corresponding cyclopentenones in low to moderate yield, while that of the substrates bearing fluorine-containing groups attached to alkynyl moiety afforded the corresponding cyclopentenones in low to high yield.

Radical-mediated synthesis of the 5,11-methanomorphanthridine ring system: formal total synthesis of montanine-type Amaryllidaceae alkaloids, (±)-montanine, (±)-coccinine and (±)-pancracine

Radical-mediated reaction of the phenyl sulfide 16 and the phenyl selenide 17 in boiling toluene or o-xylene containing AIBN gave, in moderate yields, the 5, 11-methanomorphanthridine ring system 4, which is a basic skeleton of montanine-type Amaryllidaceae alkaloids, and formal total synthesis of the title alkaloids 1–3 by conversion of 5, 11-methanomorphanthridin-2-one 5, derived from N-(4-oxocyclohex-2-enyl)-4-phenylthiotetrahydroisoquinoline 21 using this methodology, into the 2,3-benzylidenedioxy-5,11-methanomorphanthridine 31 is achieved.

Investigation of the intermolecular Pauson-Khand reaction of various 1-alkynes with cyclic exo-methylene compounds

Intermolecular Pauson-Khand reaction of various 1-alkynes with 4-exo-methylenepiperidine and -cyclohexane derivatives to give corresponding spirocyclopentenones was investigated. The reaction of m- and p-substituted arylalkynes furnished corresponding spirocyclic compounds in good yields, while that of o-substituted arylalkynes and 1-hexyne proceeded in nil to moderate yield.

Approaches to the total synthesis of montanine-type alkaloids: a first synthesis of (±)-4a,11a-cis-11,11a-anti-5,11-methanomorphanthridine and its trans-isomer

The title compounds (3) and (4) were synthesised by reductive cyclisation of cis- and trans-11-hydroxymethyl-N-tosylmorphanthridines (15) and (16) derived from cis- and trans-nitrocyclohexane derivatives (5) and (6) with sodium bis(2-methoxyethoxy)aluminium hydride in boiling toluene.