Vinylic substitution polycyclizations

The alkaloids of the cinchona bark are natural products containing a quinoline structure [111]. Examples are the diastereoisomeric pairs quinine/quinidine and cinchonidine/cinchonine 108 and 109 in which a 4-methylquinoline unit is bonded to a vinyl-substituted quinuclidine system (1-azabi-cyclo[2.2.2]octane). Camptothecin 110, a highly toxic polycyclic quinoline alkaloid, was isolated from the stem wood of the Chinese tree Camphoteca acuminata (Nyssaceae). 

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. 

The Lewis acid-promoted reaction of our oximinosulfonate with dienes and the conversion of the resulting cycloadducts to pyridines comprises a new annulation method for the synthesis of substituted pyridines from conjugated dienes. As illustrated in the Table, very good overall yields are obtained in reactions of 2-substituted dienes, providing 5-substituted pyridine-2-carboxylates. Reactions with 1-substituted dienes yield 3-substituted pyridines, and disubstituted dienes react smoothly to afford trisubstituted pyridines in good yield. Polycyclic systems are obtained when dienes such as 1-vinyl-1-cyclohexene are employed in the annulation. 

Intramolecular HAS induced by reducing reagents has been intensively applied to obtain a large number of compounds, where either alkyl, vinyl, aryl, or heteroaryl radicals successfully add onto arenes [31b, 40]. Different synthetic strategies, such as ring expansion [41], ipso substitution [42], 1,5-hydrogen translocation, and tandem cyclization [43], among others, have been applied to afford important cyclic compounds such as phenanthridines [44], polycyclic arenes [45], 6//-benzo[c] chromen-6-ones [13a], and strained helicenes [46]. 

In 2001, Mauleon et al. reported an unusual palladium-cascade arylation of a,P-unsaturated phenyl sulfones 23 under Heck reaction conditions [12]. Contrary to the work of Fuchs and others [13], Mauledn et al. described the intermolecular reaction of a,P-unsaturated sulfones with a large excess of iodobenzene (or / -substituted iodoarenes) in the presence of Ag COj as base, which occurred mainly through a complex cascade reaction in which three molecules of iodobenzene and one molecule of vinyl sulfone were involved, forming fused polycyclic compounds 25 rather than the Heck trisubstituted olefin expected. The authors propose a mechanism involving Heck reaction and C-H activation pathways (Scheme 6.5). 

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