Kiyoshi Nishitani

A facile synthesis of bicyclic α-methylene-γ-lactones by intramolecular cyclization of allylsilylated aldehydes☆

Abstract Bicyclic α-methylene-γ-lactones were synthesized employing intramolecular reaction of an aldehyde unit with a β-ethoxycarbonylallylsilane function by the action of TiCl 4 in an excellent yield.

Intramolecular reaction of β-(alkoxycarbonyl)allylsilane with epoxide into α-methylene-δ-lactones fused to carbocycles

Abstract Intramolecular cyclization of ω-epoxy-β-ethoxycarbonylallylsilane ( 1 ) was effected with Lewis acids to give a good yield of 5- exo -cyclization products ( 5 and 6 ), and a small amounts of 6- endo -product ( 7 ). The 5- exo -products were converted into α-methylene-δ-butyrolactone ( 6La and b ) fused to cyclopentane.

Asymmetric synthesis of α-methylene-γ-butyrolactones fused to carbocyclic rings via the Hosomi reaction of chiral allylsilanes.☆

Abstract Optically active α-methylene-γ-butyrolactones fused to five or six-membered carbocyclic ring were synthesized in 64–92% enantiomeric excess using the intramolecular Hosomi reaction of ω-formylated β-(chiral)alkoxycarbonylallylsilanes.

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.

Total Synthesis of (±)-Cembranolide via Cr(II) Mediated Intramolecular Macrocyclization of b-Alkoxycarbonylallyl Halide

The ω-formyl-β-methoxycarbonylallyl halide (20), prepared from geraniol and methyl β-hydroxypropionate, was cyclized efficiently and with high stereoselectivity to 14-membered cis-cycloalkenol (21) by CrCl 2 in DMF. The cycloalkenol was treated with p-TsOH to give an excellent yield of (±)-cis-cembranolide (VI)

Microbial Hydroxylation of (−)-α-Santonin by Aspergillus niger☆

Abstract The microbiological transformation of a sesquiterpene lactone, (−)-α-santonin was carried out by using Aspergillus niger MIL 5024 and MIL 5025. Strain MIL 5024 brings about the transformation of (−)-α-santonin (400 mg) to 11-hydroxy-(−)-α-santonin (P1) (50.4 mg), 3,6,9-trihydroxy-9,10-seco-selina-1,3,5(10)-trien-12-oic acid-12,6-lactone (P2) (22.4 mg), and 3,6-dihydroxy-9,10-seco-selina-1,3,5(10)-trien-9,12-dioic acid-12,6-lactone (P3) (27.1 mg), which were isolated and characterized by UV, IR, mass and 1H-NMR spectroanalyses. All of these products are described for the first time. Results similar to those with MIL 5024 were also obtained from the transformation of (−)-α-santonin by the other isolate, strain MIL 5025.

Investigation of intramolecular pauson-khand reaction of 2-aryl-1,6- and 1-methyl-1,7-enynes (exo-olefins) and 1-phenyl-1-octen-7-yne (endo-olefin)

The intramolecular Pauson-Khand reaction of various 2-aryl-1-hepten-6-ynes and its aza-derivatives (exo-olefins) efficiently produced aryl-bicyclo[3.3.0]octenones and azaoctenone bearing quaternary carbon centers at angular positions in good yields. Although a similar reaction of 2-phenyl-1-octen-7-yne (exo-olefin), which is a homologue of 2-phenyl-1-hepten-6-yne, did not take place, the reaction of the methyl derivatives smoothly proceeded. However, the reaction of regioisomeric 1-phenyl-1-octen-7-yne (endo-olefin) afforded the desired product in moderate yields.

Microbial hydroxylation of 11,13-dehydrosantonin by Aspergillus nigert☆

Abstract The microbial transformation of a sesquiterpene lactone, 11,13-dehydro-(−)-α-santonin (DS), was carried out by 7 fungi. Although 6 of the fungi transformed the substrate into three (one fungus) or fewer (5 fungi) kinds of products, Aspergillus niger MIL 5024 gave five products including all of those produced by the others. The products were identified by UV, IR, mass, and 1 H-NMR spectroanalyses as (−)-α-santonin (P1), 11-hydroxy-(−)-α-santonin (P2), 13-hydroxy-(−)-α-santonin (P3), 3,6,9-trihydroxy-9,10- seco -selina-1,3,5(10)-trien-12-oic acid- 12,6-lactone (P4), and 8- epi -artemisin (P5). P3, a new compound, was also produced by A. niger MIL 5035, but P4 and P5 were produced only by strain MIL 5024. The biosynthetic pathway of these 5 products from DS was estimated.

AN ALTERNATIVE REGIOSELECTIVE RING-OPENING OF EPOXIDES TO CHLOROHYDRINS MEDIATED BY CHLOROTITANIUM(IV) REAGENTS

A regioselective cleavage of various epoxides to vic-chlorohydrin isomers by using TiCl 4 or TiCl 4 -Ti(O-i-Pr) 4 complex was investigated. The less substituted alcohols, C2-attack products, were formed by the use of TiCl 4 in CH 2 Cl 2 . On the other hand, the less substituted chlorides, Cl-attack products, were formed by using TiCl(O-i-Pr) 3 in DMF. These regioselectivities depend on both the acidity of the Lewis acids and the polarity of the solvents.

A facile method for conversion of phenolic tetrahydroisoquinolines to benzylamines with ring cleavage

The reaction of N-cyanomethyl-6- and -8-hydroxytetrahydroiso-quinolinium methiodide with various amines afforded the corresponding benzylamines via the formation of p- or o-quinone methide in moderate to high yields.