Allenes insertion

A tandem enolate-arylation-allylic cyclisation, in which an essential z-butyldimethylsilyl ether protecting group delays the cyclisation step until the Pd-catalysed arylation is complete, enables 1-vinyl-l//-[2]benzopyrans 54 to be prepared from 2-bromobenzaldehyde (Scheme 32) <00CC1675>. 4-Substituted isochromans 55 are formed from aldehydes by a Pd-catalysed termolecular queuing cascade. The sequence involves cyclisation of an aryl iodide onto a proximate alkyne followed by an allene insertion. Transmetallation with indium then allows addition to the aldehyde (Scheme 33) . 

In an alternative strategy functionalized phenols, such as iodophenol, were involved in palladium-catalyzed carbonylation of alkynes or allenes, producing coumarin or chromone derivatives (Scheme 23) [130-133]. After oxidative addition of the iodoarene to the Pd(0) catalyst the order of insertion of either CO or the unsaturated substrate mainly depends on the nature of the substrate. In fact, Alper et al. reported that CO insertion occurs prior to allene insertion leading to methylene- or vinyl-benzopyranone derivatives [130]. On the contrary, insertion of alkynes precedes insertion of CO, affording couma-rine derivatives, as reported by Larock et al. According to the authors, this unusual selectivity can be explained by the inability of the acyl palladium species to further react with the alkyne, hence the decarbonylation step occurs preferentially [131-133]. 

Allenes insert into ir-allyl complexes so as to generate new ir-allyl species (equation 78).248 The insertion of 2-r-butyl-1,3-butadiene into ir-allylpalladium complexes proceeds normally, but is then followed by an unusual cyclization reaction, presumably due to the disposition of the butenyl frag-... 

Aluminum-carbon bonds, CO and allene insertion, 3, 267 Aluminum(0)-carbon interactions, characteristics, 9, 250 Aluminum(I)-carbon interactions, characteristics, 9, 250 Aluminum(III)-carbon interactions, characteristics and studies, 9, 247 Aluminum catalyst system... 

Palladium chemistry has been used in the synthesis of tetrahydroisoquinolines. Different combinations of iodoaryl-amine-alkene can be used in these multicomponent reactions. For example, the metal-mediated o-alkylated/alkenyl-ation and intramolecular aza-Michael reaction (Scheme 109) give moderate yields of heterocycle <2004TL6903>, whereas the palladium-catalyzed allene insertion-nucleophilic incorporation-Michael addition cascade (Equation 172) produces good yields of tetrahydroisoquinolines in 15 examples <2003TL7445> with further examples producing tetrahydroquinolines (Scheme 110) <2000TL7125>. 

Chromans possessing a fused isoxazolidine moiety 505 can be accessed via a palladium-catalyzed allene insertion-intramolecular 1,3-dipolar cycloaddition cascade reaction between ( )-fV-(2-hydroxybenzylidene)methanamine oxide, allene, and aryl iodides. This process creates two rings, two stereocentres and a quaternary carbon centre in one-pot (Equation 210) <2002CC1754>. 

Six fused isoxazolidines of general structure 110 were synthesised through a new palladium-catalysed allene insertion-intramolecular 1,3-DC cascade reaction. The m-ring junction stereochemistry of 110 was established by X-ray analysis <02CC1754>. 

The eventual product of such reactions (after cleavage of the Zr-C bond during workup [51]) is an amine with a vinyl or alkyl substituent (arising from the alkyne or alkene) at the a position. Whitby thus derivatized tetrahydro-quinoline, following in situ generation of the zirconaaziridine 26, by alkyne, alkene, or allene insertion (Eq. 11) [52,53]. 

Primary amines reacted via a palladium-catalysed allene insertion-nucleophilic incorporation-Michael addition cascade to give isoquinoline derivatives. The yields were good and fifteen examples are reported <03TL7445>. 

SPS of isoxazolidines through 1,3-dipolar cycloaddition and their transformations have been reviewed <2005CSR507>. Isoxazolidines were also prepared by nitrone 1,3-dipolar cycloaddition on silica gel in solvent-free conditions under microwave irradiation <2001J(P1)452>. Fused polycyclic isoxazolidines were prepared via a multi-component palladium-catalyzed allene insertion-intramolecular 1,3-dipolar cycloaddition cascade <2002CC1754, 2005AGE7570>. 

Allylic alkylation catalyzed by Pd(dba)2 and ( PrO)3P has been used for incorporation of nucleobases (pyrimidines and purines) into carbocyclic nucleoside analogs. In certain cases, unstabilized nucleophiles have been found to participate in allylic alkylation reactions. For example, an aUenic double bond is sufficiently nucleophilic to react with the r-aUyl complex generated upon heating Pd(dba)2 and 1 in toluene (eq 15). Formation of the trans-fused product (2) was interpreted to arise via the double inversion pathway commonly observed in conventional Pd-catalyzed allylic alkylation reactions. Interestingly, changing to a coordinating solvent (CH3CN) resulted in allene insertion into the r-allyl complex to form the isomeric c/s-fused product (3). 

Efficient domino reactions of the alkenyl iodide 453 with CO, aUene, and piperidine proceeded to give 456 in very high yield (80 %) after six-step reactions [172], CO is the most reactive, and CO insertion is followed by olefin insertion to generate 454. Then allene insertion occurs after the second CO insertion. Finally, the TT-allylpalladium intermediate 455 is trapped by the amine to yield 456. 

Although the majority of processes of this type involves alkyne insertion into the reactive C-CN species, examples of allene insertions have been demonstrated with cyanoformate and with alkynyl cyanide substrates (Scheme 3-106). ... 

Dondas, H.A., Bahne, G., Clique, B. et al. (2001) Synthesis of heterocycles via sequential Pd/Ru-catalysed allene insertion-nucleophile incorporation-olefin metathesis. Tetrahedron... 

Grigg, R., Liu, A., Shaw, D. et al. (2000) Synthesis of quinol-4-ones and chroman-4-ones via a palladium-catalysed cascade carbonylation-allene insertion. Tetrahedron Lett., 41,7125-8. 

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]. 

The first route we saw in Section 5.1 the second and third resemble the synthetic reactions most commonly used for alkyl complexes. In Eq. 5.15 and Eq. 5.16, the metal reacts with the sterically slim terminal CH2 group, and Eq. 5.17 shows an electrophilic attack on a diene complex. Equation 5.18 shows that when a C=C group of a diene undergoes insertion into an M-H bond, the hydrogen tends to add to the terminal carbon (Markovnikov s rule). The resulting methylallyl can become if a vacant site is available. In Eq. 5.19, when an allene inserts into an M-H bond, the hydride adds to the central carbon to give an allyl. 

Allene insertion/nucleophile incorporation can also be combined with 1,3-dipole cycloaddition as an efficient protocol for the synthesis of various fused polycycles. In 2005, Dondas et al. used this strategy to synthesize various nitrogen- or oxygen-containing fused polycycles such as 323 through intermediate azomethine ylides, azomethine imines, and nitrones [112] (Scheme 6.85). 

The plausible mechanism of the catalytic reaction involves (1) oxidative addition (2) double bond insertion into the Pd-H bond with formation of / -allyl palladium intermediate and (3) reductive elimination (Scheme 8.23) [85]. In a similar way allene insertion into the Pd-H bond as a key-step of the catalytic cycle... 

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