Cycloaddition of o-quinones

Adduct 100 is formed from the 1,4 cycloaddition of o-quinone (99) with the morpholine enamine of cyclohexanone (125). Treatment of styrene oxide with cyclic enamines at elevated temperatures (about 230°C) produces O.N-ketals possessing a furan nucleus (125a). 

The use of ultrasonic (US) radiation (typical range 20 to 850 kHz) to accelerate Diels-Alder reactions is undergoing continuous expansion. There is a parallelism between the ultrasonic and high pressure-assisted reactions. Ultrasonic radiations induce cavitation, that is, the formation and the collapse of microbubbles inside the liquid phase which is accompanied by the local generation of high temperature and high pressure [29]. Snyder and coworkers [30] published the first ultrasound-assisted Diels-Alder reactions that involved the cycloadditions of o-quinone 37 with appropriate dienes 38 to synthesize abietanoid diterpenes A-C (Scheme 4.7) isolated from the traditional Chinese medicine, Dan Shen, prepared from the roots of Salvia miltiorrhiza Bunge. 

Wang, J. Pettus, L. H. Pettus, T. R. R. Cycloadditions of o-quinone dimethides with p-quinol derivatives regiocontrolled formation of anthracyclic ring systems. Tetrahedron Lett. 2004, 45, 1793-1796. 

Cinchona alkaloid derivatives catalysed the enantioselective 4 + 2-cycloaddition of o-quinones with ketene enolates to produce chiral o-quinone cycloadducts in high ee... 

Drawing from their success with catalytic [4 + 2] cycloaddition, Lectka group developed another highly enantioselective cycloaddition of o-quinone methide (o-QM) with silyl ketene acetals, using a chiral cinchona alkaloid derived ammonium, N-(3-nitrobenzyl)quinidinium fluoride Is, as a precatalyst. The free hydroxyl group of the cinchona alkaloid moiety was crucial to high optical induction. A variety of silyl ketene acetals had been screened to afford the cycloadducts 22 with good ee (72-90%) and excellent yield (84—91%) (Scheme 10.26) [35]. 

Scheme 10.26 Cycloaddition of o-quinone methide with silyl ketene acetal.

The thermal and photochemical [4 + 2] cycloadditions of o-quinones with olefinic and acetylenic dienophiles have been extensively reviewed4,5,200 and include their 4tt heterodiene Diels-Alder reactions with olefins,201-204 vinyl ethers,205 enamines,206 selected dienes,207-209 dipheny-lketenimines,210 ketenes,209,210 fulvenes,211 and selected heterocycles including furan,207-209,212 benzofuran,209,212,215 indoles,213 azepines,214 and 1,2-diazepines.214 The tetrahalo-substituted o-quinones, tetrachloro- and tetrabromo-o-quinone, generally participate in heterodiene [4 + 2] cycloadditions at an increased rate over the unsubstituted systems and generally provide higher overall yields of the Diels-Alder products.4,5 With simple olefins, the dienophile geometry is maintained in the course of the thermal [4 4- 2] cycloadditions [Eq. (52)],203,204... 

Two recent reports have detailed the [4 + 2] cycloadditions of o-quinone methides with heterodienophiles, thiones [Eq. (43)]168... 

Full details of a careful study of the regio- and stereospecific intramolecular [4 + 2] cycloadditions of o-quinone methides generated by the thermal or acid-catalyzed (CF3CO2H) dehydration of o-hydroxybenzyl alcohols have been described 75 and have found application in the total synthesis of enantiomerically pure (3/ )-26 and (3/ )-27 possessing the ring system and correct absolute configuration of the cannabinol family [Eq. (47)]. 

The intramolecular cycloaddition of o-quinone methide N-alky1imines with alkenes to form six-membered nitrogen rings is well documented but the intermolecular reaction is less well characterised. Ito et al. have now shown that the o-quinone methide N-alkylimines (182), generated in situ by treatment of the corresponding N-trimethylsilyltrimethylammonium salts (181) with fluoride ion, react with the electron-deficient alkenes (183)... 

Unexpectedly, a completely different reaction took place in the oxidation of 2-(l-propenyl)phenol (111) with PdCh. Carpanone (112) was obtained in one step in 62% crude yield. This remarkable reaction is explained by the formation of o-quinone, followed by the radical coupling of the side-chain. Then the intramolecular cycloaddition takes place to form carpanone[131]. 

A further variation on this general method for preparing quinoxaline dioxides is the use of o-quinone dioximes (54) rather than benzofurazan 1-oxides. The dioxime undergoes cycloaddition with cr-dicarbonyl and a-hydroxycarbonyl compounds, and hydroxamic acids of type 55 are particularly easily prepared by this method.56... 

Derivatives of o-quinones react with enamines to form oxazines. In this reaction, o-quinones themselves form dioxanes [88JCS(P1)151]. The authors assume that the reaction proceeds by a stepwise [4 + 2]-cycloaddition with the formation of intermediates 242. Dioxanes are also formed by... 

The photoinduced 1,4-cycloaddition of alkenes to phenanthra-quinone to give substituted 1,4-dioxenes [Eq. (86)] in good yield was first observed in 1944.824 The addition has since then been more fully investigated, and is applicable to a variety of o-quinones and aromatic... 

A number of other photochemical 1,4-cycloadditions leading to the formation of heterocyclic systems have been reported, but in general these are less well investigated. The irradiation of o-quinones in the presence of sulfur dioxide affords, often in good yield, the corresponding 1,3,2-dioxathiole or cyclic sulfate 338 [see, for example, Eq. (91)]. Reaction of phenanthraquinone with triphenylphosphine can be achieved photochemically339 or thermally and the product is thought to have the cyclic structure (317). 

Later, Lectka et al. reported a detailed synthetic and mechanistic study of unusual [4 + 2] cycloaddition of ketene enolates and o-quinones by the bifunctional catalysis of cinchona alkaloids BQD la (or BQN lb) and Lewis adds. The undertaken investigations based on the integration of experimental and calculated data itself demonstrated a surprising cooperative LA/LB interaction on a ketene enolate. It showed that the reaction of o-quinone undergoes a mechanistic switch in which the mode of activation changes from Lewis acid (LA) complexation of the quinone to metal complexation of the chiral ketene enolate. 

Lower reaction temperatures favor the reversible formation of the Diels-Alder products, and higher reaction temperatures promote the irreversible ene reactions. Related observations of the competing or predominating intramolecular Diels-Alder reactions of a-cyano or a-acetyl a,/3-unsaturated esters have been reported in studies of the thermal and Lewis acid-promoted ene reaction (Table 7-II, entry 16).143 The complementary use of o-quinone methide intermediates in intra- as well as inter-molecular [4 + 2] cycloaddition reactions is discussed in the following section. 

A third difference from thermal reactions is the lack of stereospecificity in photochemical 1,4-cycloadditions. This can be shown by reaction of o-quinones with olefins, a process that, with careful choice of the olefin, proceeds mainly as addition to give 1,4-dioxenes (although 1,2-cycloaddition to give oxetane derivatives is also possible) , viz. 

The utility of 141 was emphasized by a recent synthesis of idarubicinone (9) [146] (Scheme 30). Cycloaddition of quinone 143, prepared from 141 by ketalization and cerimn ammonimn nitrate (CAN) oxidation [20], with a novel precursor of o-quinone dimethide [146], tran -, 2-bis(trimethylsilyloxy)benzocyclobutane (142), and subsequent removal of protecting groups gave idarubicinone (9) in 65% overall yield. 

Scheme 7.56 Metal-catalyzed generation of o-quinone methides and subsequent cycloaddition reactions.

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