Quinone monoketals 5+2 cycloadditions

Here again, the cycloaddition is endo-selective, with only regioisomers 79 being formed, and, when using 2- and/or 3-substituted furans, only the unsubstituted furan double-bond reacts in these inverse electron-demand Diels-Alder processes [134-136]. Indoles, pyrroles, and thiophenes can also be made to react as dienophiles with ortho-quinone monoketals... 

Oxidation of orr/to-alkoxyphenols in alcohol solvents leads to highly reactive ortho-quinone monoketals, which undergo spontaneous dimerization unless appropriately substituted. In one useful example of such a [4 -f 2]-cycloaddition, monoketal (XXXVIII), derived from constant current electrolysis of phenol (XXXVII), dimerized to give the neolignan natural product asatone (XXXIX) in 34% yield [45] ... 

For the preparation of 2,3-dihydrobenzo[6]furans, several strategies have been developed. The acid-catalyzed cycloaddition of styrenes (e.g., (135)) with quinone monoketals is suitable for the synthesis of both 2,3-dihydrobenzofurans and the quinonoid derivatives (Scheme 93) <77JA8073,... 

As described earlier, quinone monoketals (e.g., 139) are not only good substrates for the DPM reaction, but they also participate in acid-catalyzed [5+2]cycloaddition reactions with styrene derivatives (e.g., p-methylstyrene) to givebicyclo[3.2.1]octenediones (e.g., 140) that can themselves participate in ODPM processes to give multiftinctional, donor-acceptor cyclopropanes (e.g., 141). The last type of conpound can participate in fiirther reactions generating several additional and novel scaffolds that may be useful in drug discovery settings. Meanwhile, iminium ethers that are readily derived from [5+2] cycloadducts of type 140 participate in ADPM rearrangements. 

Fig. 14 Isoxazolines synthesis through 1,3-dipolar [3+2] cycloaddition reactions between ortho-quinone monoketals and benzonitrile oxides...

Intramolecular Diels—Alder reactions of ort/m-quinone monoketals into bicyclo [2.2.2]octane ring systems were also used by Chen s group in the three syntheses of the Fab-inhibitory antibiotic platencin (and analogues thereof) that they reported in 2011 [126]. For example, inspired by Liao s work, they prepared the phenolic (/ )-alcohol 227 (90% ee), which was treated with DIB in MeOH to afford the ortho-quinone dimethyl monoketal 228. This MOB was heated in toluene to trigger its [4 +2] cycloaddition, which preferentially occurred via a chair-like transition state displaying the OH group in an equatorial orientation (see 228 in Fig. 55) to furnish... 

A series of substituted coumestans 87 were synthesized by Liu, Wang, and coworkers through the formal [3 + 2] cycloaddition of quinone monoketals 85 and the thiomethyl-substituted coumarin 86 (Scheme 39) [138]. The reaction, catalyzed by tin tetrachloride, involves an allylic substitution/intramolecular cyclization/thiol elimination sequence. 

Debenzoyltashironin, a densely functionalized polycyclic natural product that induces neurite outgrowth in fetal rat cortical neurons, was synthesized by Danishefsky and co-workers using a biomimetic synthetic route. As shown in Scheme 20.4, the cyclic quinone monoketal 10 was formed by oxidative dearomatization of 9 followed by intramolecular O-cyclization. The transannular Diels-Alder cycloaddition was observed during this process. However, a 4-minute microwave irradiation was needed to complete the reaction to give 11 in 65% yield. It is remarkable that such a complex polycyclic ring system was assembled in two steps. Incorporation of a trisubstituted allene as the dieno-phile of 9 was important because the transannular Diels-Alder reaction did not proceed when an alkene dienophile... 

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