Oxacycles annulated

Based on a transformation described by Catellani and coworkers [61], the Lautens group [62] developed a three-component domino reaction catalyzed by palladium for the synthesis of benzo annulated oxacycles 6/1-114 (Scheme 6/1.30). As substrates, these authors used a m-iodoaryl iodoalkyl ether 6/1-113, an alkene substi-... 

Scheme 6/1.30. Postulated mechanism for the reaction of 6/1-113 to give annulated oxacycles 6/1-113.

Flash-vacuum pyrolysis has been used in a general annulation protocol for the synthesis of fused carbocyclic and oxacyclic ring systems of type (Tables 1 and 2). The pre-... 

Cumulated yhdes enter into domino addition-intramolecular Wittig olefination reactions with a- and P-hydroxy or amino aldehydes and ketones to afford imsaturated five- and six-membered oxacycles or azacycles, respectively. In this way o-hydroxyaryl aldehydes were converted with 2 into the corresponding annulated pyrans, while pyrrolizines were obtained from 2-acylpyrroles [18]. Fiuther apphcations of this approach have been reported more recently. Andrus et aL [19] prepared the enantiomerically pine pyrrolenone 6 by reaction of yhde 2 with N-Boc protected aldehyde 5 in 60% yield. Plans by this group to use 6 as an intermediate en route to the im-... 

Based on a transformation described by Catellani and coworkers [80], Lautens s group [81] developed a series of syntheses of carbocycles and heterocycles from aryl iodide, alkyl halides and Mizoroki-Heck acceptors. In an early example, the authors described a three-component domino reaction catalysed by palladium for the synthesis of benzo-annulated oxacycles 144 (Scheme 8.37). To do so, they used an m-iodoaryl iodoalkyl ether 143, an alkene substimted with an electron-withdrawing group, such as t-butyl acrylate and an iodoalkane such as -BuI in the presence of norbomene. It is proposed that, after the oxidative addition of the aryliodide, a Mizoroki-Heck-type reaction with nor-bornene and a C—H activation first takes place to form a palladacycle PdCl, which is then alkylated with the iodoalkane (Scheme 8.37). A second C—H activation occurs and then, via the formation of the oxacycle OCl, norbomene is eliminated. Finally, the aryl-palladium species obtained reacts with the acrylate. The alkylation step of palladacycles of the type PdCl and PdCl was studied in more detail by Echavarren and coworkers [82] using computational methods. They concluded that, after a C—H activation, the formation of a C(sp )—C(sp ) bond between the palladacycle PdCl and an iodoalkane presumably proceeds by oxidative addition to form a palladium(IV) species to give PdC2. This stays, in contrast with the reaction between a C(sp )—X electrophile (vinyl or aromatic halide) and PdCl, to form a new C(sp )—C(sp ) bond which takes place through a transmetallation. 

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