Palladium-mediated Cyclization Research Articles

Stereocontrolled Synthesis of 2‐Alkenyl‐4‐methylene Tetrahydropyrans.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereocontrolled synthesis of 2-alkenyl-4-methylene tetrahydropyrans

A variety of 2-alkenyl-4-methylene tetrahydropyrans were synthesized via consecutive transition metal-catalyzed bond forming processes. In this approach, ruthenium-catalyzed coupling of homoallylic carbonates and homopropargylic alcohols generates substrates containing the requisite functionality for a palladium-mediated cyclization, thereby providing concise access to the target structures. The installation of a trisubstituted alkene at the C-2 position was achieved using an olefin cross metathesis process.

Synthesis of Pyrrolopyrimidine CRF-R1 Antagonists Containing a Tricyclic Core via an Intra-molecular Heck Reaction

A synthetic route to pharmaceutically important tricyclic pyrrolopyrimidines was developed. The method employs a palladium-mediated Heck cyclization as the critical step in the construction of the final six membered ring.

A Straightforward Entry to Functionalized Carbo- and Heterocycles Based on Pd-Mediated Cyclizations

The efficient and practical syntheses of functionalized carbo-and heterocyclic compounds have been achieved employing a process based on an intramolecular palladium-mediated cyclization coupled with a carbon-carbon bond forming reaction.

Observations on the Intramolecular Heck Reactions of Aromatic Chlorides Using Palladium/Imidazolium Salts.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Cyclisations Involving Attack of Carbo- and Heteronucleophiles on Carbon-Carbon π-Bonds Activated by Organopalladium Complexes

In the late 1980’s, a new process based on an intramolecular palladium-mediated cyclisation coupled with a carbon-carbon bond forming reaction appeared in the literature. Since the first report, many novel ring systems have been synthesized using this methodology. The aim of this present review article is to summarise a number of synthetic applications of this new process developed over the last fifteen years.

Observations on the intramolecular Heck reactions of aromatic chlorides using palladium/imidazolium salts

The intramolecular Heck reaction of aromatic amines and ethers using palladium/imidazolium salts is described. The use of tetra- n-butylammonium halide salts facilitates the reactivity of aromatic chlorides. An unexpected and novel palladium-mediated cyclisation is also described leading to the formation of a tricyclic adduct.

Transition metal control in the reaction of alkyne-substituted phenyl iodides with terminal alkynes: Sonogashira coupling vs cyclic carbopalladation

Reaction between terminal alkynes and phenyl iodides bearing a tethered alkyne unit can be effectively controlled by the nature of a transition metal catalyst. Whereas the use of Pd(0)/Cu(I) promotes the expected Sonogashira coupling to give phenyl alkynes, the absence of the copper co-catalyst triggers a palladium-mediated cyclisation providing 1,2-dihydroacenaphthylene, 1 H,3 H-benzo[ de]isochromene, (1 Z)-1-(2-propynylidene)-2,3-dihydro-1 H-indene and (4 E)-4-(2-propynylidene)-3,4-dihydro-1 H-isochromene derivatives. In the latter Pd-catalysed two-component process, the product distribution depends on the structure of alkyne-substituted phenyl iodides, terminal alkynes and secondary amines used as solvents. The proposed reaction mechanism reflects a competitive formation of intermediary σ-(acetylide) vs π-alkyne Pd(II) complexes.

Short syntheses of (+/-)-delta-araneosene and humulene utilizing a combination of four-component assembly and palladium-mediated cyclization.

[reaction: see text] The four components shown are assembled in two steps, and the product is converted to araneosene by a short sequence.

Palladium-Mediated Cyclization on Carbohydrate Templates Synthesis of Enantiopure Annelated Tricyclic Compounds

Various bromo unsaturated carbohydrates 2−4 have been prepared from ethyl and aryl 4,6-di-O-acetyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranoside by deacetylation, followed firstly by monosilylation with TBDMSCl and then by alkylation with 2-bromobenzyl bromide or 1-bromo-bromomethylcycloalkene. The N-, C-, and O-analogues 6−8 were prepared by palladium-mediated alkylation of the carbonate 5 with TsNHCH2−C6H4-o-Br, (CO2Me)2CH−C6H4-o-Br, and HOC6H4-o-I, respectively. The threo analogue 10 was obtained using the same methodology as for 2, after inversion of configuration at C-4 by means of a Mitsunobu reaction. Treatment of the unsaturated carbohydrates 2−4, 6−8, and 10 with a catalytic amount of Pd(OAc)2/PPh3 in DMF in the presence of Bu4NHSO4 and NEt3 afforded the annelated tricyclic compounds 11−13 and 15−18 in good yields when the anomeric substituent was the p-tert-butylphenyl group, via an intramolecular Heck reaction followed by a β-alkoxy-palladium elimination

Palladium-mediated formation of bowl-shaped PAHs: synthesis of as-Indaceno

Bowl-shaped fullerene fragments, as-indaceno[3,2,1,8,7, 6-pqrstuv]picenes, can be synthesized by a double palladium-mediated cyclization in good to excellent yield. The structure of 1, 8-dimethyl as-indaceno[3,2,1,8,7,6-pqrstuv]picene was confirmed by X-ray analysis. The high yields, mild reaction conditions, and wide range of functional group tolerance are advantages of this method over existing FVP and reductive coupling routes to bowl-shaped PAHs.

Palladium-Mediated Cyclization on Carbohydrate Templates. 3. Extension of The Cyclization to the Threo Series.

ABSTRACT The palladium(0)-catalyzed Heck-type cyclization-β-alkoxy elimination reaction leading to enantiopure bicyclic compounds in the case of erythro 2,3-unsaturated glycosides has been successfully extended to the threo stereoisomer by only changing the aglycon moiety from an ethoxy group to an aryloxy moiety.

Radical and Palladium-Mediated Cyclization of Ortho-Iodo Benzyl Enamines: Application to Solid Phase Synthesis

Radical and Palladium-Mediated Cyclization of <i>Ortho</i>-Iodo Benzyl Enamines: Application to Solid Phase Synthesis

Radical and Palladium-Mediated Cyclizations of Ortho-Iodo Benzyl Enamines: A Scope and Limitation Study

Radical and Palladium-Mediated Cyclizations of <i>Ortho</i>-Iodo Benzyl Enamines: A Scope and Limitation Study

Palladium-Mediated Cyclization on Carbohydrate Templates. 2. Synthesis of Enantiopure Tricyclic Compounds

The bromo substituted unsaturated carbohydrates 3a−f were prepared from 3,4,6-tri-O-acetyl-d-glucal by Ferrier reaction with the appropriate allylic or homoallylic alcohol, deacetylation followed by monosilylation with TBDMSCl, and then alkylation with BrCH2CBrCH2. The N- and C-analogues 4a,b were synthesized by palladium alkylation of the intermediate carbonate with TsNHCH2CBrCH2 and (MeO2C)2CHCH2CBrCH2, respectively. Treatment of the unsaturated carbohydrates 3a, 4a, and 4b with a catalytic amount of Pd(OAc)2/PPh3 in CH3CN/H2O, in the presence of Bu4NHSO4 and NEt3, afforded the tricyclic compounds 5, 6, and 7, respectively. Under the same conditions, the analogue tricyclic compounds 8, 9, and 10 were formed starting from 3b−d. In the case of compounds 3e and 3f, the formation of the bicyclic glucal 11 via an already described β-alkoxyelimination was only observed. Moreover, trapping of the σ-alkylpalladium intermediate obtained from 3e with an external nucleophile yielded the 2-deoxy carbohydrate 12 and the 2,3-unsaturated sugar 13, using respectively sodium formate and sodium tetraphenylborate.

Palladium-Mediated Cyclization on Carbohydrate Templates. 1. Synthesis of Enantiopure Bicyclic Compounds

The bromo unsaturated carbohydrates 3a and 9 were prepared from ethyl 4,6-di-O-acetyl-2,3-dideoxy-d-erythro-hex-2-enopyranoside (1a) and (7) by deacetylation followed by monosilylation with TBDMSCl and then alkylation with BrCH2CBrCH2. The threo analogues 6 and 10 were obtained using the same methodology after inversion at C-4 via a Mitsunobu reaction. The N- and C-analogues 4b and 5 were prepared by palladium alkylation of the carbonate 2d with TsNHCH2CBrCH2 and (CO2Me)2CHCH2CBrCH2, respectively. Treatment of the unsaturated carbohydrates 3a and 9 with a catalytic amount of Pd(OAc)2/PPh3 in CH3CN/H2O in the presence of Bu4NHSO4 and NEt3 afforded the bicyclic compound 14a. The N- and C-analogues 14b and 14c were obtained using the same conditions and starting, respectively, from 4b and 5. On the other hand, treatment of the threo derivatives 6 and 10 under these conditions gave the furanic structure 15. In the case of compound 3a, performing the reaction in the presence of sodium formate yielded the bicyclic 2-deoxy carbohydrate 17.

Palladium-mediated cyclisation on carbohydrate templates A new route to bis-annulated pyranosides

A new and efficient route to bis-annulated pyranosides by palladium(0)-catalysed cascade cyclisation is described. The appropriate 2,3-unsaturated allylglycosides are subjected to Heck reaction under smooth Jeffery's conditions to produce the tricyclic derivatives in good yields.

An unexpected palladium-catalysed cyclisation on carbohydrate templates

Alkyl 4-O-bromoalkenyl α-Δ2-glycopyranosides 1 undergo a palladium-mediated Heck-type cyclisation providing bicyclic glycals 4 in good yields via a syn-dealkoxypalladation pathway.

Synthesis of a nucleoside analog bearing a branched difunctional sidechain using the palladium-mediated cyclization of a γ-oxoallene

The aldehyde 8 was synthesized in high yield and with excellent stereoselectivity by treating a protected 3-hydroxypropanal with Corey's chiral B-propargyl boradiazoline reagent. Cyclization of this γ-oxoallene with palladium(II) in the presence of methanol and carbon monoxide produced the furanoside 9 with excellent stereoselectivity for the D-deoxyribose geometry. The furanoside 9 was converted to the branched extended sidechain deoxythymidine analog 11 by reduction, protection, and β-stereoselective Vorbruggen coupling. The hydroboration/oxidation of 10 to yield the doexyribofuranoside analog 13, bearing two sidechain hydroxyl groups, was also demonstrated.

Palladium-mediated cyclization of 1,5-hexadien-3-ols to 1-methyl-1,3-cyclopentadienes

Treatment of 1,5-hexadien-3-ols in acetic acid by Pd(0) [Pd(PPh 3) 4] led to 1-methyl-1,3-cyclopentadienes. Cyclization is improved by the presence of catalytic amount of trifluoroacetic acid. Mechanism is discussed from the observed results with deuterated alcohols.