Sequencing palladium-catalyzed cycloisomerization cascades in a synthesis of the gelsemine core.

Transition metal-catalyzed cycloisomerization is a powerful strategy for the construction of cyclic organic molecules, and the use of palladium catalysts can deliver a wide range of monocyclic and bicyclic products. However, applications of cycloisomerizations in complex target synthesis in which more than one cycloisomerization process is deployed in a cascade context are rare. Here we report investigations of the relative rates of two different types of ene-ynamide cycloisomerization that form fused and spirocyclic rings, and use of these results to design a sequence-controlled cascade cycloisomerization that prepares the tetracyclic core of gelsemine in a single step. Crucial to this work was an evaluation of the kinetics of each cycloisomerization in competition experiments, which revealed a key influence of the ynamide electron-withdrawing group on the cycloisomerization reaction.

Diastereoselective Syntheses of Spiro[indoline-3,4'-pyridin]-2-yl Carbamates via AgOTf/Ph3P-Catalyzed Tandem Cyclizations of Tryptamine-Ynesulfonamides.

Spiro[indoline-3,4'-piperidine] is a significant structural scaffold in numerous polycyclic indole alkaloids with a variety of bioactivities. In this study, a synthetic strategy was developed to access spiro[indoline-3,4'-pyridin]-2-yl carbamate via an AgOTf/PPh3-catalyzed tandem cyclization of tryptamine-ynesulfonamides. The unique feature of this strategy is the efficient intermolecular capturing of the in situ generated spiroindoleninium intermediates with carbamates, leading to the diastereoselective syntheses of spiro[indoline-3,4'-pyridin]-2-yl carbamate derivatives. A broad scope of this cyclization was demonstrated by a variety of tryptamine-ynesulfonamide substrates and several carbamates. A plausible mechanism of this reaction was proposed.

Gold(i)-catalyzed pathway-switchable tandem cycloisomerizations to indolizino[8,7-b]indole and indolo[2,3-a]quinolizine derivatives.

Experimental and theoretical explorations were performed on the pathways of the cascade cycloisomerizations of tryptamine-N-ethynylpropiolamide substrates. The methodology provided a common strategy to access either indolizino[8,7-b]indoles or indolo[2,3-a]quinolizines in a switchable fashion.

N-Fluorobenzenesulfonimide as a highly effective Ag(i)-catalyst attenuator for tryptamine-derived ynesulfonamide cycloisomerization.

N-Fluorobenzenesulfonimide (NFSI) was identified for the first time as a highly effective Ag(i)-catalyst attenuator in the annulation of a tryptamine-derived ynesulfonamide to azepino[4,5-b]indole derivatives. Substrate tolerances were examined thoroughly and a plausible mechanism was proposed. The interaction between the Ag(i) catalyst and NFSI was probed by density functional theory (DFT) calculations. This study provided a highly efficient method to synthesize azepino[4,5-b]indole derivatives.

A gold-catalyzed cycloisomerization/aerobic oxidation cascade strategy for 2-aryl indenones from 1,5-enynes.

A unique gold(i)-catalyzed 5-endo-dig cyclization/aerobic oxidation cascade strategy from 1,5-enyne substrates with molecular oxygen as the oxidant to yield the indenone was described. The reaction mechanism was studied by heavy atom labelling and some related experiments. This method was applied to the formal total synthesis of isoprekinamycin.