Organocatalytic Intramolecular Ring-Closing Alkylation And Palladium-Catalyzed Ring-Opening Thiocarbonylation

Polycyclic indoles such as tetrahydrocarbozoles(THCs),tetrahycdro-p-carbolines (THBCs),tetrahydro-pyrano[3,4-b]indoles(THPIs) have diverse and remarkable biological activity.The pharmaceutical potential of these compounds has stimulated the development of new and efficient catalytic routes for their preparation.In the presence of Grubbs' second-generation catalyst Ru-C627,variousω-indolylα,β-unsaturated aldehydes were prepared successfully using cross metathesis reactions.A new methodology for the synthesis of enantioriched polycyclic indoles was developed by asymmetric organocatalytic intramolecular ring-closing Friedel-Crafts alkylations of the indolylα,β-unsaturated aldehydes.Few examples have been reported in the literature for the synthesis ofα,β-unsaturated aldehydes with functional groups though powerful ruthenium-catalyzed cross-metathesis reaction.Using Hoveyda-Grubbs' second generation catalysts,we have succesfully prepared several substituted 5-(indolyl-3/2)-α,β-unsaturated aldehydes though cross metathesis reactions.By using diarylprolinol sillyl ether DAPSE-597 and 3,5-dinitrobenzoic acid as catalysts,optically active C-1 substitued THCs were synthesized by intramolecular ring-closing Friedel-Crafts alkylations in high enantioselectivity(up to 98%ee). Enantioriched C-4 substitued THCs were prepared(up to 91%ee) in the presence of imidazolidinone S,S-246 and trifluoroacetic acid as the catalytic systems though intramolecular ring-closing Friedel-Crafts alkylations.Several indolylα,β-unsaturated aldehydes were synthesized successfully under Ru-C627 of the corresponding indolyl allyl ethers prepared from the corresponding carboxlate with crotonaldehyde.With S,S-246 and 3,5-dinitrobenzoic acid as the catalysts, the synthesis of enantioriched THPIs(up to 93%ee) were carried out by intramolecular ring-closing Friedel-Crafts alkylations of the indolylα,β-unsaturated aldehydes.The absolute configuration of the alkylation product was determined to be R by X-ray crystallography of the alcohol which cotaining an bromide atom.In the presence of imidazolidinone S,S-246 and cyanoacetic acid,we have prepared enantioriched C-4 substitued THBCs(up to 93%ee) by asymmetric organocatalytic intramolecular ring-closing Friedel-Crafts alkylations of the corresponding α,β-unsaturated aldehydes.The formation of a thiocarbonyl unit and employing thiols and thiophenols as a direct substrate represents one of the most challenging subject in transition-metal-catalyzed reactions.In this regards several vinylcyclopropanes(VCPs) were prepared.The reaction conditions such as the catalyst system,solvent,temprture,the pressure of CO and so on were optimized for the ring-opening thiocarbonylation of VCPs,thiols,and carbon monoxide.It was shown that Pd(OAc)2 with PPh₃ was the best catalyst system to form the corresponding unsaturated thioesters in moderate to excellent yields.