Cascade Reactions Involving Allenes

CASCADE REACTIONS INVOLVING ALLENES 6.4.1 Cascade Reactions of Monoallenes... 

The transition metal catalysis of this tandem (cascade) reaction involving [3,3]-sigmatropic rearrangement (since it would be the carbonyl oxygen of the acetate forming a new bond to the p-acetylenic atom) followed by the formal Myers-Saito cyclization of allene 3.524 results in the formation of aromatic ketones 3.525 in up to 94% yield (Scheme 3.29) [265]. 

Grigg and Xu have developed a variety of so-called queuing cascades involving allenes. The intra-intermolecular carbopalladation sequence of the <9-iodo-A-methyl-A -(methylallyl)aniline 142 and 1,1-dimethylallene 143 with subsequent / -dehydropalladation leads to the 1,3-dienyl-substituted indole derivative 144, which is immediately trapped by an added dienophile (e.g., A-methylmaleimide) in a Diels-Alder reaction to yield 145 (Scheme 37)7 ... 

A one-pot sequential and cascade sequence involving the formation of allylic azides, from aryl/heteroaryl/vinyl halides, allene and sodium azide, by palladium catalyzed anion capture, and cyclization-anion capture, followed by 1,3-dipolar cycloaddition provided a variety of 1,2,3-triazoles in good yields <01T7729>. Reaction of a,P-acetylenic aldehydes 107 with sodium azide in dimethylsulfoxide followed by hydrolysis afforded 5-substituted-4-carbaldehyde-1,2,3-triazole derivatives 108 <01TL9117>. 

Since AA is only a minor fatty acid in higher plants, eicosanoids are not of major importance for plant physiology. However, the oxygenation metabolites of linoleic acid and a-linolenic acid, called oxylipins [5,6], do play a role in plant defence reactions, in the formation of phytohormones and in the synthesis of cutin monomers [6,40-43]. Oxylipins constitute a family of lipids that are formed from free fatty acids by a cascade of reactions involving at least one step of dioxygen-dependent oxidation. The biosynthesis of oxylipins proceeds via a large number of metabolic pathways, most of which involve an unsaturated hydroperoxy fatty acid as intermediate (Scheme 10). Conversion of the hydroperoxide via the peroxide lyase pathway, the allene oxide pathway and the recently discovered peroxygenase pathway, leads to a complex pattern of oxidized lipid mediators. 

Conjugated systems, including 1,3-butadienes, diene-allenes, enyne-allenes, enediynes, dienediynes, and enediallenes, were synthesized via organoboranes. A wide array of cascade cyclization reactions involving high energy intermediates, such as o-isotoluenes, biradicals, o-quinodimethanes, benzocyclobutadienes, and enyne-ketenes, were initiated from these unsaturated compounds. 

By starting from the enyne-allene 27, the o-quinodimethane 28 was captured in an intramolecular Diels-Alder reaction to give 29 having the tetracyclic steroidal skeleton (Scheme 6) (19,20). It is worth noting that this cascade reaction could involve an energy loss of more than 100 kcal/mol with conversion of four n bonds in 27 to four o bonds in 29 along with the formation of a benzene ring. 

Conceptually similar palladium-catalyzed cascade reactions have been developed, involving molecular-queuing cycloaddition, cyclocondensation and Diels-Alder reactions [71], cydization-anion-capture-olefin metathesis [72], carbonylation-allene insertion [73], carbonylation/amination/Michael addition [74], sequential Petasis reaction/palladium-catalyzed process [75], supported allenes as substrates [76], and palladium-ruthenium catalysts [77]. 

In 2010, Malacria and coworkers developed a novel Au-catalyzed cyclization of 1,6-enyne 9, furnishing allene-substituted tetrahydrofuran 11 in excellent yield. The proposed mechanism involves an initial enyne cyclization to generate the cationic gold-vinyl complex 10 and subsequent unexpected [l,5]-hydride shift. Deuteration experiments support the [l,5]-hydride shift and rule out the inter-molecular scrambling. This cascade reaction is unusual because the cyclization precedes followed by an uncommon [l,5]-hydride shift (Scheme 12.5) [9]. 

In 2007, a gold(I)-catalyzed cascade reaction of diynes and electron-rich aromatics and heteroaromatics for the synthesis of complex a-pyrones was successfully realized by Schreiber and Luo (Scheme 12.13) [16]. This reaction involves the [3,3]-sigmatropic rearrangement of the diynes 25 to an yne-allene intermediate 26, which is supported by the observed racemization of enan-tioenriched substrates. Gold(I)-induced a 6-endo-dig cyclization of intermediate 26 would give the oxocarbenium intermediate 27, which could be trapped by electron-rich aromatics and heteroaromatics to afford complex a-pyrones 28. 

AUenes comprise the second class of privileged substrates for gold catalysis. They can be transformed into various functionalized structures, many via cascade processes. Several reactions involving in situ-generated allenes have been discussed so far (see Schemes 4.9,4.11,4.15, and 4.20 to 4.23), but in this section we focus on reactions that begin with allenes. 

Very recently, Ma has reported a rhodium-catalyzed route to 18,19-norsteroid skeletons from bis-allenes, involving a cyclometallation-carbometallation-reductive elimination-Diels-Alder reaction cascade process.410... 

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