Iterative Cationic Cyclizations for the Synthesis of Polycyclic Targets

 

Iterative Cationic Cyclizations for the Synthesis of Polycyclic Targets

 

Date: 13^th January, 2025 (Monday)

Time: 5:30 - 6:30 pm (HKT)

 

Prof. Alison Frontier

University of Rochester

 

The development of new iterative cyclization strategies for rapid assembly of complex molecules will be described. These strategies have arisen from our work on the Nazarov pentannulation; an electrocyclic, cationic cyclization that occurs diastereospecifically. The reaction cascades combine halo-alkynyl Prins chemistry and halo-Nazarov cyclization chemistry, through a series of cationic intermediates. The cationic cascades resemble classical polyene cyclization, but follow irregular patterns to deliver a variety of densely functionalized scaffolds in one or two steps. A range of fused and spirocyclic ring systems can be accessed, containing functionalized cyclopentanes, oxygen and nitrogen heterocycles, and a vinyl halide synthetic handle. The sequences are stereocontrolled, and can produce enantiopure adducts.

 

Strategically, the method couples two simple precursors: an enyne/ arenyne and the carbonyl derivative that serves as the initiating carbon. The initiating carbon (in blue) can be an aldehyde, ketone, imine, N,O-acetal, acetal, ketal or enol ether, and subsequent iterative cyclization converts the initiating carbon into an sp³ center (blue) within a polycyclic framework.