Dearomatization transannular Diels-Alder

Scheme 7.31. Domino oxidative dearomatization/transannular-Diels-Alder reaction.

The final type of intramolecular Diels-Alder reaction that finds wide use in natural product total syntheses is the transannular process. Danishefsky exploited the power of this transformation during an oxidative dearomatization/transannular Diels-Alder cascade in his synthesis of 11-0-debenzoyltashironin. Deslongchamps produced the tricyclic core of cassaine via a transannular intramolecular Diels-Alder reaction. The tricyclic c/5-decalin with appended macrocycle framework of superstolide A is also available using this strategy. Roush demonstrated the effectiveness of this approach by heating 140 in toluene to yield cycloadduct 141 that was transformed into superstolide A in four more steps. ... 

En route to the total synthesis oftashironin (7-114a) and the debenzoylated compound 7-114b, which shows an interesting promotion of neurite growth, Danishefsky and coworkers have developed a domino oxidative dearomatization/trans-annular Diels-Alder reaction [54]. In this line, treatment of 7-115 with phenyl-iodine(III) diacetate (PIDA) led to an intermediate 7-116, which immediately underwent a transannular Diels-Alder reaction to furnish the complex cycloadducts 7-117 in good yields (Scheme 7.31). 

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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