Heteroaryl enones

This reaction has been extended to other heteroarene carboxylates and to cycloalk-enones,leadingto conjugated aryl or heteroaryl enones ingood yields (Scheme 10.59).91... 

SCS-MP2 and the new perturbative B2-PLYP density functional methods provide accurate reaction barriers and outperform MP2 and B3-LYP methods when applied to the 1,3-dipolar cycloaddition reactions of ethylene and acetylene.39 Phosphepine has been shown to catalyse the asymmetric 3 + 2-cycloaddition of allenes with a variety of enones (e.g. chalcones) to produce highly functionalized cyclopentenes with good enantiomeric excess.40 The AuPPh3SbF6 complex catalysed the intramolecular 3 + 2- cycloaddition of unactivated arenyne- (or enyne)-yne functionalities under ambient conditions.41 A review of the use of Rh(I)-catalysed 3 + 2-cycloadditions of diaryl-and arylalkyl-cyclopropenones and aryl-, heteroaryl-, and dialkyl-substituted alkynes to synthesise cyclopentadienones for use in the synthesis of natural products, polymers, dendrimers, and antigen-presenting scaffolds has been presented.42... 

Benzotriazole was found to be an efficient ligand for the Cu(I) iodide-catalyzed N-arylation of imidazoles with aryl and heteroaryl halides <07TL4207>. The first enantioselective conjugate addition reaction of I //-benzotriazole with a variety of enones catalyzed by a cinchona alkaloid thiourea affords Michael adducts in good yields with moderate to good enantioselectivities has been reported <07S2576>. 

Unfortunately, several important classes of a-diazo ketones cannot be prepared in good yield via these standard methods. a -Diazo derivatives of a.p-unsaturated ketones, for example, have previously proved to be particularly difficult to prepare.1113 12 The acylation of diazomethane with a.p-unsaturated acid chlorides and anhydrides is generally not a successful reaction because of the facility of dipolar cycloaddition to conjugated double bonds, which leads in this case to the formation of mixtures of isomeric pyrazolines. Also problematic are diazo transfer reactions involving base-sensitive substrates such as certain a,p-enones and heteroaryl ketones. Finally, the relatively harsh conditions and lack of regioselectivity associated with the thermodynamically controlled Claisen formylation step in the "deformylative" diazo transfer procedure limit the utility of this method when applied to the synthesis of diazo derivatives of many enones and unsymmetrical saturated ketones. 

A review has discussed the photochemical cyclization of a variety of aryl- and heteroaryl-prop-2-enoic acids. Irradiation (A,>340nm) of the cyclohexenone (119) in argon purged benzene solution affords the cyclized derivatives (120) as a 3 1 mixture of diastereoisomers. The formation of the cyclopropyl group arises via the carbene (121) and insertion into a C-H bond of a neighbouring methyl group. This carbene is formed, presumably, from the biradical (122) which arises by addition of the alkene to the excited state of the enone. Further evidence for the carbene intermediate comes from a reaction in methanol when the diastereo-isomeric mixture of the ethers (123) and (124) is obtained." ... 

With respect to the substrate scope, ketones are the most efficient nucleophiles although the intermolecular reaction works also well for esters, amides and Weinreb amides (Fig. 2.7). Regarding the Michael acceptor, enones are the best electrophiles with a wide range of substituents tolerated (alkyl, aryl and heteroaryl ketones). a,p-Unsaturated esters, in the case of the intermolecular cyclopropanation, and a,p-unsaturated diimides for the intramolecular reaction, extends the substrate scope of the process (Fig. 2.7). A transition state model for the intramolecular cyclopropanation reaction has been proposed as depicted in Scheme 2.38 for catalyst 65 [106d]. In this model the ammonium salt adopts a conformation that gives the Z-enolate of the nucleophile on deprotonation with the base. The intramolecular conjugate addition of the enolate then takes place through a boat-type transition state. 

Ruthenium Conjugate addition of HCN to enones R CH=CHCOR (R = -, s-, and f-alkyl, Ph R = aryl, heteroaryl, alkyl, alkenyl), catalysed by the Ru(II) complex (289a) or (289b) (0.01-0.5 mol%) in combination with PhOLi, has been shown to produce )3-cyano ketones R CH(CN)CH2COR with <98% ee at -20 to 0°C in Bu OMe. No 1,2-adducts were detected. ... 

The first enantioselective organocatalytic oxo-Michael reaction to enones was reported by Falck [109]. Falck developed the intramolecular addition of boronic acids hemiesters to enones catalyzed by thiourea catalysts. Alkyl, aryl, and heteroaryl y-hydroxy enones react with phenylboronic acid to furnish the corresponding boronic hemiesters 118, which after oxidative cleavage of the resulting dioxaboro-lane renders the chiral 1,2 diols 119 in excellent yields and enantioselectivities (Scheme 33.34). 

Improved enantioselectivities were reached by replacing the BINAP-Ni complexes with bis(oxazoline)-Ni complexes in particular, the catalyst combination Ni(II)/(/ ,/ )-Ph-DBFOX/HFIP/2,6-lutidine was highly efficient in the enantioselective fluorination of aryl acetylthiazolidinones, up to 99% ee (Scheme 44.20). The strong Lewis acid, EtsSiOTf, used in the previous example, was replaced by the relatively strong Brpnsted acid, HFIP (1,1,1,3,3,3-hexa-fluoroisopropyl alcohol pKa = 9.3). The beneficial effect of HFIP is probably a result of an improved turnover of catalysts thanks to a faster release of the fiuorinated product in the transition state. The utility of this catalytic system was further demonstrated in the enantioselective fluorination of nonconjugated enone substrates such as 3-butenoyl derivatives and 3-heteroaryl substrates and of (3-keto esters (up to 99% ee ) and oxindoles (Scheme 44.20). ... 

A theoretical investigation into the copper hydride-catalysed hydrosilylation of 3-methylcyclohex-2-enone addressed the mechanism and ligand effects. Methallylboranes CH2=C(R)CH2B(pin) can deliver the allyl group to electron-deficient alkynes RC=CX (R = alkyl, alkenyl, heteroaryl X = CO2R, CN, CONRR, SO2R) in a Michael manner with iyn-stereochemistry in the presence of Cu(OAc)2 as catalyst. ... 

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