Domino cyclization carbopalladation

A domino Heck carbopalladation/cyclization reaction of (Z)-3-(2-(but-2-ynyloxy)phenyl)prop-2-en-l-ol 453 with aryl iodides furnishes chroman derivatives 454 in good yield (Equation 185) <2004AGE5997>. 

The same palladium-catalyzed domino cyclization-anion capture sequence involving carbopalladation of allene (69), which was employed by Grigg et al. for the synthesis of diene 70 (Scheme 10) can yield 1,3,5-hexatriene 194, when starting from 2-bromo-l-ene-6-yne 193 instead of the aryl iodide 68 (Scheme 32) [52], Under the conditions of its formation, 194 immediately undergoes thermal 67r-electrocyclization to give the bicyclic product 195. 

Based upon the studies on the mechanism of the Cl sequence we rationalized that the elusive allenol intermediate 19 (Chap. 2.2) could participate in intramolecular trapping reactions as an allenyl ether. Furthermore, vinyl allenes are perfectly suited as dienes in Diels-Alder reactions. Considering both reactive functionalities, allenyl ethers and vinyl allenes, which are perfectly suited for domino processes, we designed an insertion sequence based upon cyclizing carbopalladation [76], where the vinyl aUene results from an isomerization of an alkynylation of a vinyl... 

In 2013, Kim and coworkers reported a palladium-catalyzed domino cyclization of A-(2-bromoallyl)-A-ciimamyltosylamides for the construction of pyridines [4], The reaction proceeds via a domino 5-exo/3-exo carbopalladation, ring expansion by palladium rearrangement, and an aromatization. Various 4-arylnicotinate derivatives were produced in good yields (Scheme 2.2). 

Some examples of termination by anion capture are as follows. Reactions are terminated by carbonylation. Domino carbopalladation and carbonylation of the iododiene 163 under 1 atm of CO via a neopentylpalladium intermediate gave the cyclized ester 164 with high yield and diastereoselectivity [82], The iodide 165 underwent 5-exo cyclization to generate the neopentylpalladium 166 and its carbonylation gave the acylpalladium 167. Intramolecular attack by malonate anion affords 168 [83]. 

Intramolecular carbopalladation has widely been used to assemble the polycyclic frameworks of natural products. The majority of these carbopalladations are intramolecular Heck reactions and examples of 5-exo, 6-exo, 1-exo, -exo, 6-endo, S-endo, and macro-cyclic ring closures will be presented (Scheme 12). Examples fall into two basic categories vinylic substitution (75- 76) and quaternary center construction (77- 78). Investigation of domino reactions like polyene cyclizations (79- 80) and asynunetric Heck reactions (81 82) has been fruitful. 

Asymmetric carbopalladation can also be combined with other reactions to give domino asynunetric processes. A group selective example from a synthesis of ( capnellene 216 features the cyclization of the alkenyl triflate 210 (Scheme 32). The resultant TT-allylpalladium intermediate has effectively been captured with a variety of nucleophiles including acetate anion for the synthesis. A domino Suzuki coupling/in-tramolecular Heck reaction converts ditriflate 212 into tricycle 213 in modest yield with 85% The transformation accomplises an annnelation, two carbon-carbon bond... 

Consult Ref [37] compare Ref [38], where a similar reaction principle is reported. (3-Alkylidene) THFs with a CH2CH=0 side chain in 4-position were obtained in anelegant PdCl2-catalyzed Heck carbopalladation/cyclization domino reaction of... 

Dong et al. developed an efficient palladium-catalyzed domino carbopalladation/ cyclization via sp C—H activation and a domino carbopaUadation/cross-coupling reaction from mesityhnagnesium bromide and alkynes [68] (Scheme 6.46). Various substimted indenes 170 were constructed selectively in good yield. 

FIGURE 8 J Compilation of chromans (in a deprotected form) generated by the dontino carbopaUadation/carbopalladation/cyclization sequence. Given are the yields of the domino sequence starting from the respective diynes. 

A variety of 3-vinyl-substituted imidazo[l,5-a]indole derivatives were synthesized by intramolecular Pd catalyzed cyclization of the indole-2-carboxylic acid al-lenamides through either a domino carbopalladation/exo-cyclization process or a novel hydroamination reaction that proceeds smoothly under microwave irradiation. Both the observed pathways involve a Tu-allyl-palladium (II) complex arising from insertion of the allene group into a palladium (II) species, the latter being formed in situ by the intervention of an aryl iodide or of the N-H group. In both these cases, the role of nucleophile is covered by the indole nitrogen (Beccalli et al., 2010). 

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