Divergent Asymmetric Total Syntheses of (−)-Alloaristoteline and (+)-Aristoteline via Directed Indolization Strategies

A divergent asymmetric synthetic route to (−)-alloaristoteline and (+)-aristoteline is described. The key doubly bridged tricyclic enol triflate common intermediate prepared via enantioselective deprotonation and stepwise annulation was successfully bifurcated to complete the first completely synthetic construction of the titled natural alkaloids upon strategic implementation of the late-state directed indolization methods

New Synthetic Routes to (+)-Uleine and (−)-Tubifolidine: General Approach to 2‑Azabicyclo[3.3.1]nonane Indole Alkaloids

Novel asymmetric synthetic routes to (+)-uleine and (−)-tubifolidine are reported herein. The regioselective formation of enol triflates from 2-azabicyclo[3.3.1]­nonane ketones followed by indolizations of the resultant ene-hydrazides allowed the efficient construction of key indole intermediates, facilitating the total synthesis of the target natural alkaloids

Switching Chemoselectivity Based on the Ring Size: How to Make Ring-Fused Indoles Using Transition-Metal-Mediated Cross-Coupling

Pyrroloazocine indole alkaloids consisting of eight-membered azacycle fused to pyrrole and indole units exhibit intriguing pharmacological functions but still pose a synthetic challenge. Here, we report an alternative synthetic strategy for the pyrroloazocine indole core from two key steps: (i) regioselective Fischer indolization and (ii) transition-metal-mediated C–N cross-coupling reaction of N-Boc aryl hydrazine with azacyclic vinyl triflate. In our investigation, Pd(0)- and Cu­(I)-catalysts are found to display distinct and complementary selectivities for the ring size of cyclic vinyl triflates. For rings that are five- and six-membered, a Pd(0)-catalyst afforded the corresponding ene-hydrazines while completely ineffective for seven-membered or larger rings. A Cu­(I)-catalyst exhibited the opposite selectivities. Computational studies reveal that their ring size dependency is due to the two bottlenecks of reductive elimination for Pd and oxidative addition for Cu along with bond strengths in products and reactants and degree of stage at transition states. These findings led us to establish a straightforward protocol for accessing a variety of ring-fused indoles highlighted with the formal synthesis of (−)-lundurine A