Scientists gain control over molecular building blocks by tweaking temperature
Chemists have cracked a long-standing problem in drug synthesis: making the same starting material form two different products on command, simply by changing reaction temperature. The breakthrough could accelerate development of pharmaceuticals and specialty chemicals by giving manufacturers more flexibility in how they build complex molecules.
Originaltitel: Harnessing Entropy for Switchable Radical Cyclization Cascades
Radical cyclizations are highly selective and useful transformations in complex molecule synthesis. However, the regioselectivity of radical cyclizations is often determined by substrate structure, and in most cases, selective for 5-exo cyclization products over the 6-endo regioisomer. Herein, we address this challenge using a reaction-condition engineering approach to afford selective access to both the 5-exo and 6-endo radical cyclization products of the same substrate. The approach utilizes temperature to control the kinetic favorability of the 5-exo radical intermediate to engage in either carbon–carbon bond formation through Giese addition to deliver 5-exo functionalized products, or a one-carbon ring expansion to deliver the 6-endo functionalized product. We display this switchable cyclization approach on heteroaryl radical intermediates generated from single electron reductions of heteroaryl halides and on aryl radical intermediates generated via halogen atom transfer. Additionally, density functional theory supports that the kinetically favorable pathway is determined by reaction temperature.