Diels-Alder cycloaddition of juglone derivatives. 2. Regiospecificity of reactions leading to tetracyclic anthracyclinone systems

Angucyclines: Total syntheses, new structures, and biosynthetic studies of an emerging new class of antibiotics

“…Regioselectivity of some Diels-Alder reactions [74] Ketene acetals such as 81 and juglone (47) form predominantly regioisomers derived from 1,8-dihydroxy-9,10-anthraquinone. This clearly follows previous experimental results [78,79,80] and theoretical frontier orbital considerations [81]. The regiochemical outcome results from an energetically favorable transition state in which the two larger orbital coefficients of dienophile LUMO and diene HOMO overlap.…”

Origins of Regioselectivity of Diels−Alder Reactions for the Synthesis of Bisanthraquinone Antibiotic BE-43472B

“…Fundamental studies of regiocontrol in Diels-Alder cycloadditions between juglone and juglone derivatives with a variety of dienes have been performed, notably by Trost,11 Kelly12 and Boeckmann 13. The rationale for the observed regioselectivity in cycloadditions of juglones with polar dienes is based on the presence of a strong internal hydrogen bond in juglone between the phenol proton and adjacent carbonyl.…”

“…This internal Brønsted acid coordination polarizes the π-system of juglones so that the most electrophilic site is the carbon atom β to the hydrogen-bonded carbonyl (C-2 in Figure 2). 14 This regioselectivity is found to be dependent upon diene polarity,13 with weakly-polarized dienes typically giving lower selectivities than more highly-polarized dienes, however, Lewis acid catalysts may also be used to influence regiochemical control 11. In Nicolaou’s key Diels – Alder reaction between 2 and 3a (Scheme 1), the more nucleophilic, unsubstituted diene terminus is found to attack α to the aromatic substituent of the dienophile, at C-3.…”

OC022: Quality control in the measurement of nuchal translucency in the first trimester of pregnancy

“…In Diels–Alder reactions with juglone methyl ether 28 , the main factor in the regiocontrol of cycloadditions with electron‐rich dienes, is the electron donating effect of the 5‐OMe substituent (Figure 2), which makes the C‐4 carbonyl the less electron‐withdrawing substituent on C 2 C 3 double bond. As a result, the value of the coefficient of the LUMO of the C‐1 carbonyl remote from the OMe group become larger and the dienophilic double bond of 28 is polarized as shown 36e. The presence of a sulfoxide at C‐2 in juglone methyl ether derivative 5 , reinforces the polarization effect of the OCH 3 group and cooperates in the regiochemical control of Diels–Alder reactions 12.…”