Transannular processes

In all these cases, we dealt with precursors bearing a ring, which generally serves as a template or as a radical acceptor. Many excellent reviews and book chapters have covered radical tandem reactions [5]. Herein, we will focus on two distinct approaches to radical cascades. The chapter will be devoted to the construction of polycyclic structures (at least 3 rings). We will deal with two distinct approaches the first one focussing on the use of acyelic precursors, the second one based on transannular processes. 

From the literature, we can highlight four distinct strategies aiming at the construction of tricyclic or tetracyclic frameworks, based on cascade radical combinations of (C) intra - one (or two) transannular processes, (D) transannular - intra processes, (E) macrocyclization - two transannular processes, (F) two (or three) transannular processes inside a macrocycle (illustration of each strategy is shown on Scheme 29). 

First, he designed the iodotrienone 138 to prepare 6,6,5-tricyclic framework 141, via a l3-endo macrocyclization - a (5-cxo/lO-enJo) followed by a 6-exo/6-endo) transannular closure. Under the BusSnH-AIBN protocol, a unique saturated ketone was isolated. It proved to be the unexpected cis-anti-trans 5,7,5-tricyclic ketone 142 (Scheme 39). The sequence begins with a Michael-oriented l3-endo macrocyclization to furnish the a-oxo-cyclotridecadienyl radical 139. The first transannular process generates the predicted oxo-cyclodecenyl radical 140, which, however, prefers the 5-exo/l-endo) mode of cyclization to yield the isolated ketone 142... 

Radicals constitute another type of reactive intermediate that have found considerable use in synthesizing seven-membered rings. Pat-tenden provides a rather remarkable example of the way this process can be incorporated into a macrocyclization-transannulation cascade to prepare polycycles. Tributyltin hydride generates a radical intermediate which, upon macromolecular ring closure and two subsequent transannular processes, provides a tricyclic product (Eq. 8)." Aside... 

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. ... 

BIOSYNTHESIS OF DITERPENES BASED ON CATIONIC CYCLIZATIONS, 1,2-SHIFTS, AND TRANSANNULAR PROCESSES 281... 

Efficient synthesis of the medium- and macrocyclic substrates and the ability to predict the stereoselectivity are the prerequisites for successful application of transannular reactions. Whereas the development in organic synthesis in the past few decades has led to new methods for preparation of these cyclic compounds, systematic exploration of transannular reactions has been rare. Indeed, besides the Diels-Alder reactions, transannular reactions were mostly studied in isolated examples as part of method development of general, nontransannular transformations. However, with continued interests in this powerful strategy and significant advances in computational methods and hardware, which can be used to predict the stereochemical course of transannular processes with increasing accuracy, there is no doubt that innovative transannular transformations will continue to emerge and be used in applications with increasing sophistication and efficiency. 

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