Fumio Miyake

A stereocontrolled synthesis of trans-alkene isosteres of dipeptides

Abstract A general synthetic route to trans-alkene isosteres of protected dipeptides is reported. This sequence permits the fullystereocontrolled preparation of these isosteres in optically active form and in quantities sufficient for further biological study. Prepared in this manner were alkene isosteres of TyrAla. PhePhe, and LeuLeu.

A Novel Synthesis of β‐Lactone Precursors of Pyramidalized Alkenes.

β-Lactone precursors 11 and 12 of pyramidalized alkenes 3,n = 1and 2, have been synthesized by a two-step route involving transannular Paterno-Buchi reaction of methyleneketones 7 and 8, followed by RuO4 oxidation of the resulting oxetanes 9 and 10. Evidence for the formation of alkene 3,n = 2, by pyrolysis of 12 is presented.

Experimental and theoretical studies on physicochemical properties of novel six-membered cyclic α-monocarbonyl azo-compounds

The preparation and physicochemical properties of a novel six-membered α-monocarbonyl azo-compound are reported. Low-temperature oxidation of 4,4-diaryl-3,4-dihydrophthalazin-1(2H)-ones (2) with lead tetra-acetate (LTA) in the presence of triethylamine in, CH2Cl2 afforded 4,4-diarylphthalazin-1(4H)-ones (3). Molecular orbital (MO) calculations on the model compound (8) of (3) disclosed on comparison with the corresponding azo-compound (7) and the αα′-dicarbonyl azo-compound (9) that the FMO properties of (8) are markedly different from that of (9). Thus, (8) should be a poor dienophile unlike (9), and analyses of the bond population indicated that (8) would undergo ready nitrogen extrusion as well as (7) and indeed, (3) was stable only below –60 °C. The MO calculations also indicated inherent 1,2-migration of the 4-substituent to the N(3) atom. 1,2-Aryl migration of (3) in acidic CH2Cl2 solution results in the formation of 3,4-diaryl-1-oxidophthalazinium betaine derivatives (13).

Antarafacial role of an aromatic nucleus; a novel regiospecific [π4a + π2a] intramolecular cycloaddition of the ene-ketene with an aromatic ring

Abstract The thermally generated ene-ketene undergoes a facile and regiospecific intramolecular cycloaddition with N,N-dimethylaniline to result in the novel formation of the azulenone derivative via a norcaradiene intermediate.

Six-membered cyclic α-monocarbonyl azo-compounds; a novel rearrangement of 4,4-disubstituted 1(4H)-phthalazinone to 3,4-disubstituted-1-oxidophthalazinium betaine

Abstract The characterization (IR) and evaluation of the reactivity (MO calculation) on one series of six-memebered cyclic α-monocarbonyl azo-compound are presented. A competitive process involving a novel acid catalyzed rearrangement and the nitrogen extrusion is also described.

A novel regiospecific intramolecular cycloaddition of an aromatic ring. Molecular orbital study of conjugated ketenes thermally generated from six-membered α-monocarbonyl azo-compounds

When a methylene dichloride solution containing 4,4-diarylphthalazin-1(4H)-one(3) was warmed above –50 °C, nitrogen extrusion occurred to result in the formation of the quinonoid ketene (19). The quinonoid ketene thus generated underwent a facile and regiospecific intramolecular [π4a+π2a] cycloaddition with NN-dimethylaniline to afford a norcaradiene (22), followed by ring opening to an azulenone derivative (14). It was found, however, that this process takes place only with an aromatic ring bearing strong electron-donating substituents such as dialkylamino groups. FMO analyses based on the model system calculated by the CNDO/2 method showed that the dominant HOMO–LUMO interaction in the transition state should involve the HOMO of NN-dialkylaniline and LUMO of the quinonoid ketene. Thus, the in-plane π*-orbital induces the orthogonal approach of the two components favouring an antarafacial pathway and the cyclisation is initiated by preferential bond formation between the central carbon of the ketene moiety and the para-carbon of NN-dialkylaniline to result in the formation of (22).

Molecular orbitals of conjugated ketenes and analysis of the intramolecular cycloaddition

Abstract MO calculations by CNDO/2 method on some conjugated ketenes were carried out. Several special features obtained and the evaluation of a role of the in plane π*-orbital for the intramolecular ene-ketene cycloaddition are described.

Molecular orbital quantities of conjugated ketenes and influence of structural variations on their electronic features

Abstract MO quantities by CNDO/2 method on several valence isomeric ketenes and structurally corresponding allene molecules were calculated to evaluate the influence of structural feature on magnitude of back-donation of oxygen n-electrons in ketene, and to rationalize an unusual cycloaddition involved in diphenyl ketene.