A new multi-output PT-QSRR model to correlate and predict the enantioselectivity and yield of Heck–Heck cascade reactions has been developed.

Ar apid and efficienta ccess to aw ide variety of enantiomerically enriched C-11b substituted lycorane analoguesc an be achieved via ac atalytic asymmetric Heck-Heck 6-exo/6-endo cascade reaction in the presence of (R)-BINAP.

The intramolecular palladium‐catalyzed reaction of N‐(iodoarylalkyl)pyrroles can be applied for the selective synthesis of medium‐sized rings by choosing the appropriate catalytic systems to direct the reaction to the alkene or to the pyrrole nucleus. These reactions can also be extended to the corresponding heteroaryl halides. Thus, reaction conditions have been established to access selectively to (hetero)fused indolizine, pyrroloazepine and pyrroloazocine systems.magnified image

Mesityllithium (MesLi) was found to be superior to butyllithium for the formation of aryllithium intermediates by iodine–lithium exchange. Subsequent intramolecular carbolithiation of the 2‐alkenyl‐substituted ortho‐lithiated N‐benzylpyrroles proceeded efficiently when the alkene was substituted with an electron‐withdrawing group. The procedure is applicable to the construction of six‐, seven‐, and eight‐membered rings, thus, opening new routes to pyrroloisoquinolines, benzazepines, and benzazocines. Although the use of (–)‐sparteine as a chiral ligand led to low levels of enantioselection, enantiomerically pure isoquinolines could be synthesized by applying this protocol to the related pyrrolidines derived from proline, as the reactions proceeded with complete diastereoselectivity.

The generation of quaternary and tertiary stereocentres at C‐10 of the pyrroloisoquinoline skeleton through intramolecular Mizoroki–Heck reactions of 2‐alkenyl‐substituted pyrroles and pyrrolidines has been studied. The cyclizations proceeded in moderate to good yields (up to 81 %), but with low enantioselectivity when chiral phosphanes such as (R)‐BINAP were used as ligands. However, enantiomerically pure 10‐substituted pyrrolo[1,2‐b]isoquinolines were efficiently obtained by a diastereoselective approach using chiral nonracemic pyrrolidines as substrates, generating a tertiary stereocentre.