Intramolecular reactions ionic liquids

Inter- and intramolecular hetero-Diels-Alder cycloaddition reactions in a series of functionalized 2-(lH)-pyrazinones have been studied in detail by the groups of Van der Eycken and Kappe (Scheme 6.95) [195-197]. In the intramolecular series, cycloaddition of alkenyl-tethered 2-(lH)-pyrazinones required 1-2 days under conventional thermal conditions involving chlorobenzene as solvent under reflux conditions (132 °C). Switching to 1,2-dichloroethane doped with the ionic liquid l-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6) and sealed-vessel microwave technology, the same transformations were completed within 8-18 min at a reaction temperature of 190 °C (Scheme 6.95 a) [195]. Without isolating the primary imidoyl chloride cycloadducts, rapid hydrolysis was achieved by the addition of small amounts of water and subjecting the reaction mixture to further microwave irradia-... 

The intramolecular hetero-Diels-Alder reactions in functionalized 2(17/)-pyrazinones to give bicyclo adducts were found to undergo a significant rate enhancement using controlled microwave irradiation in ionic liquid doped solvents <2002JOC7904>. 

Laali et al.234 have developed a method to the highly selective pura-adamantylation of arenes (toluene, ethylbenzene, anisole) with haloadamantanes (1-chloro- and 1-bromoadamantane, l-bromo-3,5,7-trimethyladamantane) and 1-adamantanol promoted by triflic acid in butylmethylimidazolium triflate [BMIM][OTf] ionic liquid. In contrast to reactions mn in 1,2-dichloroethane, little or no adamantane byproduct was detected in [BMIM][OTf. Furthermore, no isomerization of para-tolyladamantane was observed supporting the intramolecular nature of the formation of meta isomers. In competitive experiments with benzene-toluene mixture (1 1 molar ratio), high substrate selectivities were found (kT/kB = 16-17) irrespective of the alkylating agent. This is in sharp contrast to values about unity measured in 1,2-dichloroethane. 

Compounds in this class are usually made from specific precursors with the ultimate functionalities appearing in the starting materials. Syntheses in which one new bond is formed (cyclizations) usually involve substitution or condensation reactions. Two new closures with potentially some generality have been noted in this chapter. One of the intramolecular Diels-Alder reactions (see Section 13.12.8.1) and the other RCM (see Section 13.12.8.1). The Baeyer-Villiger reaction is still very much used for the preparation of lactones. A supported catalyst and a recyclable catalyst carried in an ionic liquid have been introduced for use in Baeyer-Villiger oxidations from other areas. 

Zeitler K (2006) Stereoselective synthesis of (E)-afi—unsaturated esters via carbene-catalyzed redox esterification. Qrg Lett 8 637-640 Zeitler K, Mager I (2007) An efficient and versatile approach for the immobilization of carbene precursors via copper-catalyzed [3+2]-cycloaddition and their catalytic apphcation. Adv Synth Cat 349 1851-1857 Zhao GL, Cordova A (2007) A one-pot combination of amine and heterocyclic carbene catalysis direct asymmetric synthesis of fi-hydroxy and fS-malonale esters from a,fS-unsaturated aldehydes. Tetrahedron Lett 48 5976-5980 Zhou ZZ, Ji FQ, Cao M, Yang GF (2006) An efficient intramolecular Stetter reaction in room temperature ionic liquids promoted by microwave irradiation. Adv Synth Cat 348 1826-1830... 

The first MW-assisted intramolecular Stetter reaction was reported for the synthesis of chromanone derivatives using the imidazolium type of room temperature ionic liquids (RTILs) with thiazolium salts and Et3N as catalysts <2006ASC1826>. 

The use of chiral additives with a rhodium complex also leads to cyclopropanes enantioselectively. An important chiral rhodium species is Rh2(5-DOSP)4, which leads to cyclopropanes with excellent enantioselectivity in carbene cyclopro-panation reactions. Asymmetric, intramolecular cyclopropanation reactions have been reported. The copper catalyzed diazoester cyclopropanation was reported in an ionic liquid. ° It is noted that the reaction of a diazoester with a chiral dirhodium catalyst leads to p-lactones with modest enantioselectivity Phosphonate esters have been incorporated into the diazo compound... 

Tseng and colleagues [58] reported a three-step synthesis of fused tetrahydro-P-carbolinequinoxalinones, solely based on the use of ionic liquids as solvents. Tetrahydro-P-carboline is a central core for many biologically important indole alkaloids, and the moiety of quinoxalinone often exhibits a wide spectrum of biological activities such as being anti-HIV, antihypertensive, and a ligand for a number of protein receptors. As a first step, tryptophan methyl ester was reacted with an aldehyde to form tetrahydro-p-carboline by Pictet-Spengler cyclization that further reacted with l-fluoro-2-nitrobenzene to form iV-aryl-tetrahydro-P-carboline. Intramolecular cyclization upon a reduction reaction in step three provided the desired tetrahydro-P-carbolinequinoxalinones. The entire process was based on the use of 1-n-butyl-... 

Uwari S, Khupse N, Kumar A (2008) Intramolecular Diels-Alder reaction in ionic liquids effect of ion-specific solvent friction. J Org Chem 73 9075-9083... 

Addition reactions. By intramolecular hydroacylation in an ionic liquid, indanones are prepared in a Rh-catalyzed reaction, the metal ion in use is ligated to (R)-BINAP. ... 

The intramolecular Fujiwara-Moritani/oxidative Heck reaction was applied to the synthesis of functionalized benzo[fe]furans and dihydrobenzo[h]furans in 50-80% yields, and 15 examples are given in the article <04AG(E)6144->. Ionic liquid ([bmimJBF4) was found to be an effective solvent for the PdCl -catalyzed intramolecular Heck reaction to realize benzofurans <04TL6235>. Another palladium-catalyzed intramolecular Heck reaction between vinyl triflate and benzo[(j]furan was utilized to construct the seven-membered ring based (-)-frondosin B <04T9675>. 

A variety of 2-substituted 2//-chromenes can be obtained from the facile reaction of 2-hydroxybenzaldehydes with vinylboronic acids in ionic liquid solvents <04SL2194>. In a one-pot sequence also in an ionic liquid, a Knoevenagel condensation between O-prenylated salicylaldehydes and 4-hydroxycoumarins is followed by an intramolecular hDA reaction to yield ci5-fused chromano[4, 3 4,5]pyrano[3,2-c]coumarins e.g. 20 small amounts of the corresponding chromone are also formed <04S1783>. In like manner, cii-fused furopyranopyran derivatives have been obtained from sugar aldehydes <04TL3493>. 

The heating behavior of ionic liquids combined with organic solvents under microwave irradiation has also been the subject of a recent paper by Ondruschka and coworkers [84]. Kappe et al. have used microwaves for inter and intramolecular hetero Diels-Alder reactions of 2(ll-f)-pyrazinones using dichloroethane as a solvent with small amounts of ionic liquid as heating aids (Scheme 7.26) [85], The conventional reaction can take up to 2 days to reach completion. With the micro-wave heating the reaction time could be reduced to 50 min in the absence of the ionic liquid and only 18 min in its presence. Product yields were reported to be similar to those obtained by use of conventional heating. Interestingly, when the... 

The hetero Diels-Alder reaction of a series of functionalized 2(li-f)-pyrazinones was studied in detail by Van der Eycken et al. [58, 65]. For example, in a series of intramolecular cycioadditions of alkenyl-tethered 2(li-f)-pyrazinones 27 the reaction required 1-2 days under conventional thermal conditions (chlorobenzene, reflux, 132 °C) whereas use of 1,2-dichloroethane doped with the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate (bmimPFe) and use of micro-waves up to a temperature of 190 °C (sealed vessels) enabled the same transformations to be completed within 8-15 min. The primary imidoyl chloride cycloadducts were not isolated, but were rapidly hydrolyzed under the action of microwaves by addition of small amounts of water (130 °C, 5 min). The overall yields of 28 were in the same range as reported for the conventional thermal procedures (Scheme 11.8) [58]. 

This intramolecular ring to ring rearrangement, induced by amines, has been investigated in [BMIM][PFe] and [BMIM][Bp4]. With the exception of an acid-base equilibrium between the solvent and amine, the data seem to indicate that other interactions (such as substrate-ionic liquid, amine-ionic liquid and amine-amine) have scarce relevance, whereas the high dipolarity/polarizability of ionic liquids stabilizes the rate-determining transition state and so increases the reaction rate. 

Ionic liquids ([BMIM][PF6]) are suitable media for the Co2(CO)8-catalyzed intramolecular and intermolecular Pauson-Khand aimulation, provided that the reaction is carried out under a CO pressure of 10 bar [299]. Two diethyl allyl propargyl malonates were quantitatively converted into the relevant cydopentenones, whereas heteroatom tethered enynes gave lower yields in their cydocarbonjiation products. An example is shown in Scheme 5.2-138. The reaction also works with the direct addition of ethyldiazoacetate to imines in [BMIM][BF4] and [BMIMjfPFe] [300]. 

Scheme 6.12 Formation of benzofurans in ionic liquid by intramolecular MIzoroki-Fleck reaction.

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