Aminofluorination of Cyclopropanes: A Multifold Approach through a Common, Catalytically Generated Intermediate

Abstract

We have discovered a highly regioselective aminofluorination of cyclopropanes. Remarkably, four unique sets of conditions-two photochemical, two purely chemical-generated the same aminofluorinated adducts in good to excellent yields. The multiple, diverse ways in which the reaction could be initiated provided valuable clues that led to the proposal of a "unifying" chain propagation mechanism beyond initiation, tied by a common intermediate. In all, the proposed mechanism herein is substantiated by product distribution studies, kinetic analyses, LFERs, Rehm-Weller estimations of ΔGET, competition experiments, KIEs, fluorescence data, and DFT calculations. From a more physical standpoint, transient-absorption experiments have allowed direct spectroscopic observation of radical ion intermediates (previously only postulated or probed indirectly in photochemical fluorination systems) and, consequently, have provided kinetic support for chain propagation. Lastly, calculations suggest that solvent may play an important role in the cyclopropane ring-opening step.

Light‐Mediated Formal Radical Deoxyfluorination of Tertiary Alcohols through Selective Single‐Electron Oxidation with TEDA2+.

“…[10] However,t here is another reactivity pathwayo ffered by TEDA 2+ + C that remains greatly underexplored, that is, its use as as ingle-electron oxidant. [11] The main challenge to exploit the latter reactivity is that, given the opportunity, TEDA 2+ + C would readily react through either of the aforementioned pathways or throughu nproductive single-electron oxidationst og enerate TEDA + + .I fT EDA 2+ + C can be harnessed as a single-electron oxidant to selectively oxidize given organic molecules, it might be possible to open the door for new and interesting reactivity to be explored.…”

Fluorinative ring-opening of cyclopropanes by hypervalent iodine reagents. An efficient method for 1,3-oxyfluorination and 1,3-difluorination

“…In addition, we have found only a single fluorination based 1,3-difunctionalization reaction in the literature. Very recently, Lectka and co-workers 17 reported an aminofluorination method based on cyclopropane substrates.…”

Ring‐Opening Regio‐, Diastereo‐, and Enantioselective 1,3‐Chlorochalcogenation of Cyclopropyl Carbaldehydes

“…The transformation is achievedb yamergedi minium-enamine activation.T he enantioselective desymmetrization reaction, leadingt ot hree adjacent stereocenters, furnished the target products in complete regioselectivity and moderate to high diastereo-and enantioselectivities (d.r.u pt o15:1a nd e.r.upt o9 3:7).Because of their high strain energy (about 27.5 kcal mol À1 ) [1] cyclopropanes have been used in recent years as starting materials for the 1,3-bisfunctionalization of aliphatic chains under ring-opening conditions. Recently,t he Szabó group generated 1,3-difluorides from 1,1-disubstituted cyclopropanes, [2,3] whereas our group synthesized1 ,3-dichloridesf rom donor-acceptor cyclopropanes. [4,5] Sparr andG ilmour reported the use of aldehyde-functionalized cyclopropanes for an asymmetric 1,3-dichlorination, [6] making use of am erged iminium-enamine activation (Scheme 1).…”