Intra-intramolecular cascade

Scheme 3-29 An intra-intramolecular cascade reaction leading to heterobicycles [181bj.

Intra-intramolecular cascade reactions combined with termination by an external nucleophile provide access to various kinds of ring systems. 

Early findings by Heck et al. [149a, 337] revealed that coupling reactions of haloalkenes 126 with aUcenes 125 in the presence of secondary amines gave allylamines (Scheme 8.30 132/133 Nu = NR2). On the basis of this observation, inter-intermolecular as well as intra-intramolecular cascade reactions (Scheme 8.34) [338], the latter ones leading to a variety of bicycles (Scheme 8.35) [339], were developed. 

An inter-intra-intramolecular carbopalladation cascade, initiated by the alkenylpalladium bromide intermediate from /3-bromostyrene 74 inserting into one of the triple bonds of the diyne 73, yields the ring-annelated fulvene derivative 75 (Scheme 22). ... 

Scheme 24 Two alkyne relays in sequence in intra-intramolecular carbopalladation cascades. ...

Selective synthesis of benzene derivatives via partially intramolecular cyclic carbopalladation is considerably more complex than the corresponding all-intramolecular processes. As it is generally difficult to specify the cascade-initiation point in the Type Ha cyclization process, it would generally be the least selective path. A priori, the most favorable might be the intra-inter cascade cyclization process (Type lib), since both the point of initiation and the queuing order between the two alkynes is sharply differentiated by the fact that one is intramolecular, while the other is intermolecular. Still, in-... 

Scheme 3-22 Intra-intramolecular Heck-67T-electrocyclization cascades [172],...

Alkenes are the most common terminators for intra-intermolecular cascade processes. This is exemplified by the intramolecular benzylpalladation leading to a neopentyl relay with ensuing termination by methyl acrylate yielding a 2,2-disubstituted indane (Scheme 14). ... 

Scheme 8.23 Intra-intramolecular Heck-6jt-electrocyclization cascades [318].

The great majority of radical cascades involve sequences of intramolecular steps where the overall propagation is a unimolecular process (with the exclusion of the initiation and termination steps), and recent overviews are given in Refs 1-5. However, meanwhile many tandem reactions involving both intra- and intermolecular steps, as well as multicomponent tandem reactions, have been reported in the literature, which are compiled in recent reviews. " ... 

Abstract Radical tandem reactions—and in a wider context radical dominos or cascades—have attracted a lot of attention because of their intrinsic elegance and the construction of a hroad and sometimes unique array of molecular architectiu es they allow in a single step. This review focuses on the latest progress in the design and development of new tandem reactions. The first part is devoted to intramolecular processes the second part covers tandem and domino processes involving both intra- and intermolecular steps. The third part introduces intermolecular-only reactions. Finally, the last part focuses on tandem reactions involving both radical and non-radical elementary steps. 

Cascade reactions provide valuable strategies, especially for the construction of various carbo- and heterocyclic systems with three, four, or more annelated rings [166]. The Heck reaction has successfully been employed in various inter-inter- and intra-inter- as well as all-intramolecular reaction cascades. 

Scheme 3-36 Intramolecular tiryl-aryl as well as intra-intermolecular aryl-aryl and aryl-alkene coupling cascades [189].

Furans are also useful 4ji components for tandem Ugi condensation/intra-molecular Diels-Alder cascade reactions. For example, stirring a methanolic mixture of compounds 127-129 and benzylamine at rt provided the Ugi condensation product 130 that underwent a subsequent intramolecular Diels-Alder cycloaddition to furnish 131 in 70-90% yield (Scheme 23) (99TL1851). This methodology also allowed for a solid phase synthesis by using an ArgoGel-Rink resin as the amine component, providing cycloadducts 131 (after cleavage from the resin) in ca. 90-95% yields. 

Cascade reactions arising from sequential carbopalladations are especially valuable for the construction of various carbo- and heterooligocyclic systans with three, four, or even more annelated rings. The Heck reaction has successfully been employed in various inter-inter-, intra-inter-, as well as all-intramolecular reaction cascades (Sect. IV.3). In the carbopalladation step of the Heck reaction (Scheme 6) a new metal-carbon bond is formed, which, in principle, can undergo any of the typical reactions of a hydride elimination is not too fast. When the /S-hydride elimination is totally suppressed, the palladium species can undergo a number of reactions with the formation... 

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