Intramolecular rhodium-catalysed [2 + 2 + 2] cycloaddition of linear chiral N-bridged triynes: straightforward access to fused tetrahydroisoquinoline core.

A route for the preparation of merged symmetrical tetrahydroisoquinolines with central chirality through a rhodium-catalyzed intramolecular [2 + 2 + 2] cycloaddition involving enantiopure triynes as substrates is described. The results show that linear triynes lacking a 3-atom tether can undergo efficient cyclisation. The N-tethered 1,7,13-triynes used in our approach were easily prepared from readily accessible chiral homopropargyl amides, the basic building blocks in our approach, which were efficiently obtained by diastereoselective addition of propargyl magnesium bromide to Ellman imines. Additional substitution at the benzene rings could be attained when substituted triynes at the terminal triple bonds were employed, giving access to more complex tetrahydroisoquinolines after the rhodium-catalyzed intramolecular [2 + 2 + 2] cycloaddition. Among the different transition-metal catalysts, the Wilkinson complex (RhCl(PPh3)3) afforded higher yields in the cyclisation of linear triynes; however, triynes bearing a Br substituent at the terminal positions underwent the cyclisation more efficiently in the presence of [RhCl(CO)2]2.

Diastereoselectivity of the Addition of Propargylic Magnesium Reagents to Fluorinated Aromatic Sulfinyl Imines.

The addition of propargylmagnesium bromide to fluorinated aromatic sulfinyl imines gave homopropargyl amines with total regio- and diastereoselection. Complete reversal of diastereoselectivity can be achieved in some cases using coordinating (THF) or noncoordinating (DCM) solvents. Substituted propargylic magnesium reagents have been also tested toward fluorinated aryl sulfinyl imines affording chiral homoallenyl amines with good yields and selectivity control. DFT calculations helped to rationalize the origin of the experimental regio- and diastereoselectivities observed in each case.

Pauson-Khand reaction of fluorinated compounds.

The Pauson-Khand reaction (PKR) is one of the key methods for the construction of cyclopentenone derivatives, which can in turn undergo diverse chemical transformations to yield more complex biologically active molecules. Despite the increasing availability of fluorinated building blocks and methodologies to incorporate fluorine in compounds with biological interest, there have been few significant advances focused on the fluoro-Pauson-Khand reaction, both in the inter- and intramolecular versions. Furthermore, the use of vinyl fluorides as olefinic counterparts had been completely overlooked. In this review, we collect the advances both on the stoichiometric and catalytic intermolecular and intramolecular fluoro-Pauson-Khand reaction, with special attention to the PKR of enynes containing a fluoride moiety.

The Fluoro-Pauson-Khand Reaction in the Synthesis of Enantioenriched Nitrogenated Bicycles Bearing a Quaternary C-F Stereogenic Center.

A variety of enantioenriched fluorinated 6H-cyclopenta[c]pyridin-6-one bicycles, a scaffold present in several classes of monoterpenic alkaloids with varied biological activity, were synthesized in just five steps from simple aldehyde starting materials. The synthesis presented wide functional group tolerance and moderate to high yields and diastereoselectivities and could be carried out on a gram scale. These products were suitable for further transformations, such as hydrogenation and deprotection of the tert-butylsulfonyl protecting group.