Juglone, Diels-Alder reactions

The aqueous [4+2] cycloaddition reaction of 1,4-naphthoquinones 115 with methoxy cyclohexadiene performed in the presence of bovine serum albumin (BSA) is one of the first examples of protein-promoted Diels Alder reactions [79]. Some results are reported in Table 4.18. The globular protein does not affect the regioisomer ratio of adducts. The highest enantiomeric excess was obtained in the cycloaddition of juglone 115 (R = H) with 1-methoxy-1,3-cyclohexadiene 116. 

Chiral boron catalysts had already been widely used in a variety of reactions before they were applied in Diels-Alder reactions220. Boron catalysts were first employed in the Diels-Alder reactions of quinones with electron-rich dienes. Kelly and coworkers221 found that stoichiometric amounts of a catalyst prepared from BH3, acetic acid and 3,3 -diphenyl-l,l/-bi-2-naphthol (344) catalyzed the reaction of 1-acetoxy-l,3-butadiene (341) with juglone (342) to afford cycloadduct 343 with 98% ee (equation 96). The reaction was supposed to proceed via a spirocyclic borate complex in which one face of the double bond of juglone was effectively shielded from attack by the diene. 

A peri hydrogen bonding enables juglone to partake in a Diels-Alder reaction in a regioselective fashion [176]. The H-bonded carbonyl group becomes more highly polarized which in turn causes its p-carbon more acceptor-like. 

Guingant and Barreto [53] published the pioneering paper describing the synthesis of ochromycinone (35) by a Diels-Alder reaction. The dienone (46) was prepared from 3-ethoxy-5-methyl-cyclohex-2-enone (45) in two steps (alternatively, a diene with SPh instead of OMe could be used). The Diels-Alder reaction with juglone (47) was catalyzed with boron triacetate to overcome the somewhat poor reactivity of the electron-deficient diene 46. The primary adduct 48 could not be isolated but directly eliminated and oxidized to ochromycinone (35) (Scheme 13). 

A kinetic resolution with respect to the racemic diene 66 could be achieved in the Diels-Alder reaction promoted by a chiral Lewis acid prepared from BHj in the presence of (S)-3,3 -diphenyl-l,r-binaphthalene-2,2 -diol and juglone (47) in the synthesis of (+)-emycin A and (+)-ochromycinone (35) [66] (compare previous investigations by Kelly [67]). 

Starling from the cycloadduct of juglone and acetoxybutadiene [35]. The Diels-Alder reaction gave regio- and stereoselectively the adduct in the presence of the Lewis acid, boron trifluoride. 

Fig. 7. Synthesis of plumbagin (24) and a-caryopterone (28) from juglone through retro Diels-Alder reaction...

Representative examples of the reactions of furan (282) are shown in Scheme 6.81 [102]. The furan system can be reacted as a diene initially with in situ desulfurization to release the diene from the sulfolene. This diene can then be reacted in a subsequent Diels-Alder reaction. For example, (283) reacts with juglone to give (284). 

Keywords Juglone, styrenes, DDQ, B(OAc)3, dichloromethane, room temperature, cycloaddition, Diels-Alder reaction, angucyclinones, ll-hydroxybenz[a]anthracene-7,12-diones... 

Diels-Alder reaction with nitroalkenes as dienophiles. The B(OAc)3-promoted Diels-Alder reaction of juglone (76) with substituted styrenes (77) in the presence of DDQ produced cycloadducts (78). This methodology provides a route to the total synthesis of tetrangulol (79) and anhydrolandomycinone (80) (Scheme 24) ... 

In related investigations Valderrama et al. [47] studied the reaction of naphthoquinone (40) and juglone (47) with the ketene acetal 51. Using this oxidation state, the oxygen substituent in the product is always preserved at the terminal position of dienes (compare anthracycline chemistry [55]). Thus, the phenol ether 52 a (61 %) and smaller amounts of the phenol 52b were smoothly formed after silica gel-promoted elimination and air oxidation of the primary Diels-Alder adducts. The authors also observed base-catalyzed air oxidation to the ketone 53, analogous to similar oxidations of benzylic carbanions (compare with [56]). 

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