Palladium-mediated Ring Research Articles

ChemInform Abstract: Palladium-Mediated Ring Opening of Hydroxycyclopropanes.

The palladium-mediated ring opening of substituted cyclopropanols has been found to take place predominantly at the less substituted C−C bond. Thus, sequential application of the titanium-mediated cyclopropanation of esters and the palladium-mediated ring opening of the resulting cyclopropanols provides a convenient method for functionalizing monosubstituted olefins.

Palladium-Mediated Ring Closure Reactions. Facile Syntheses of Enantiopure Bicyclic and Tricyclic Alkenones

( R)-Carvone was used as a chiral building block. Regio- and stereoselective alkylations at C6 and C2 of ( R)-carvone and ( R)-5-isopropyl-2-methyl-2-cyclohexenone [derived from the hydrogenation of ( R)-carvone] followed by palladium-mediated ring closures afforded various enantiopure bicyclic and tricyclic alkenones. Hence, cyclization of (5 S,6 S)-2,6-dimethyl-6-( cis-3-iodo-2-propenyl)-5-isopropenyl-2-cyclohexenone ( 3) gave (4a S,5 S,8a S)-1,4,4a,5,8,8a-hexahydro-5-(methoxycarbonylmethyl)-2,5,8a-trimethylnaphthalen-1-one ( 7) as the major product, cyclization of (5 S,6 S)-2,6-dimethyl-6-( cis-3-iodo-2-propenyl)-5-isopropyl-2-cyclohexenone ( 22) produced (1 S,5 R,6 S)-1,5-dimethyl-6-isopropyltricyclo[3.3.1.0 2,8]-3-nonen-9-one ( 23), and cyclization of (2 R,5 S,6 S)-2,6-dimethyl-2-( cis-3-iodo-2-propenyl)-5-isopropenyl-3-cyclohexen-1-one ( 25) afforded (3a R,6 S,7a R)-6,7a-dimethyl-5-isopropenyl-3a,6,7,7a-tetrahydro-1 H-inden-7-one ( 26). A 1,2-rearrangement reaction of bromide 16 gave hexahydro-1 H-benzocycloheptene 17.

Asymmetric synthesis of 4-deoxyverrucarol via two types of ring expansion reactions

Asymmetric synthesis of a trichothecane analogue, 4-deoxyverrucarol (2), was carried out through two types of ring expansion reactions. First, synthesis of the racemate of 2 was investigated. Thus, 1-[1-(tert-butyldimethylsiloxy)-ethyl]-1-methoxycarbonyl-2-hexen-4-on e (10), prepared by Diels-Alder reaction, was converted into the cyclopropylidene 15. The cyclobutanone (+/-)-18 was obtained from 15 via dihydroxylation, followed by successive treatments with SO(2)Cl(2) in the presence of imidazole and Florisil. After transformation of (+/-)-18 into the vinylcyclobutanol (+/-)-19, the second ring expansion reaction was performed with Pd(OAc)(2) to provide the cyclopentanone (+/-)-20. The product was converted into the racemate of 4-deoxyverrucarol (2) through the cyclohexenone (+/-)-22, but the diastereoselectivity during the introduction of the double bond was unsatisfactory. The selectivity was improved in the case of the asymmetric synthesis. The optically active cyclobutanone (+)-18 was prepared via AD reaction of 15 with 73% ee. After the transformation of (+)-18 into the cyclohexanone (-)-30 through the palladium-mediated ring expansion reaction, (-)-30 was subjected to the diastereoselective deprotonation reaction using the chiral amide. The key synthetic intermediate (-)-25 of 4-deoxyverrucarol (2) was synthesized in an optically pure form by taking advantage of a kind of kinetic resolution that occurred during the deprotonation step.

Palladium-mediated ring opening of hydroxycyclopropanes

[reaction: see text] The palladium-mediated ring opening of substituted cyclopropanols has been found to take place predominantly at the less substituted C-C bond. Thus, sequential application of the titanium-mediated cyclopropanation of esters and the palladium-mediated ring opening of the resulting cyclopropanols provides a convenient method for functionalizing monosubstituted olefins.

Total Synthesis of (±)-Scirpene

The racemate of scirpene, 12,13-epoxytrichothec-9-ene, was synthesized from 3-methoxyacetophenone. The key step in the synthesis is the palladium-mediated ring expansion reaction of the vinylcyclobutanol derivative, prepared via the oxidative ring expansion reaction of the cyclopropylidene. (3S*)-3-[(1S*,6S*)-3-Methyl-9-oxabicyclo[4.3.0]non-2-en-6-yl]-3-methyl-2-methylenecyclo-pentan-1-one formed from the reaction was converted into (±)-scirpene through the ring opening of tetrahydrofuran part, followed by cyclization for construction of the desired skeleton.

Chiral cyclobutanones as versatile synthons: the first enantioselective total synthesis of (+)-laurene

A novel and convenient route to the thermodynamically unstable ketone 11via the cyclopentanone 8 which was synthesised by palladium-mediated ring expansion of the chiral siloxyvinylcyclobutanes 9 and 10 has been developed. This leads to an enantioselective total synthesis of (+)- laurene 1.

Reactivity of (3-chloro-2-methylenecycloalkyl)palladium chloride dimers: a palladium-mediated ring homologation - functionalization approach to 4-aryltropones related to colchicine

Reactivity of (3-chloro-2-methylenecycloalkyl)palladium chloride dimers: a palladium-mediated ring homologation - functionalization approach to 4-aryltropones related to colchicine