Alkyne multistep transformation

In an imaginative construction of the angular triquinane ( )-hirsutene (158), Oppolzer and Robyr reported the carbonylative closure of allylic carbonate 155 to yield bicyclooctanes 156 and 157 (Scheme 6-27) [57]. In this multistep transformation, a alJylpalladium intermediate arising from the allylic carbonate 155 undergoes intramolecular Heck insertion of the pendant alkyne. Carbonylation of the resulting vinylpalladium intermediate, another Heck cyclization, and a second carbonylation then provide a mixture of acids, which after esterification yield esters 156 and 157 in good yield. 

Nickel(0)-catalyzed [2 + 2 + 2] cocyclization of the precursor (177) in the presence of several chiral ligands afforded the chiral tetrahydroisoquinoline (178) in a novel asymmetric cycloaddition. Compound (178) could be transformed into the benzo[a]quinolizidine (180), albeit in modest enantiomeric excess, through a multistep route involving extension of the alkynic side chain at C-1 to yield (179), introduction of a cu halogen atom, reduction of the triple bond, A(-deprotection and final eyelization (Scheme 29) <94J0C6133>. 

Traditionally, synthetic approaches toward this framework were charactoized by a lack of generality, involving poorly available starting material that require multistep synthetic transformations [22-25]. More recent approaches include tandem cleavage of hydrogenated / -and a-carbolines [26], ring closing metathesis [27], and metal-catalyzed Friedel-Crafts-type reactions of indole derivatives with several electrophiles (such as alkynes, alkenes or epoxides) (see Refs. [118] and [133] in Chap. 1 [28-32]). 

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