Bimolecular coupling reactions through oxidatively generated aromatic cations: scope and stereocontrol

Abstract

Chromenes, isochromenes, and benzoxathioles react with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to form stable aromatic cations that react with a range of nucleophiles. These oxidative fragment coupling reactions provide rapid access to structurally diverse heterocycles. Conducting the reactions in the presence of a chiral Brønsted acid results in the formation of an asymmetric ion pair that can provide enantiomerically enriched products in a rare example of a stereoselective process resulting from the generation of a chiral electrophile through oxidative carbon–hydrogen bond cleavage.

Stereocontrolled Cyanohydrin Ether Synthesis through Chiral Brønsted Acid-Mediated Vinyl Ether Hydrocyanation

“…22 Silylated nucleophiles can be utilized when a silyl group scavenger is formed upon oxocarbenium ion generation. 17a,23 All reported cases of bimolecular additions into oxocarbenium ions utilized either sterically hindered nucleophiles 22a or highly specific electrophiles. 17a,22g,23 Asymmetric Brønsted acid-catalyzed additions of silylated nucleophiles to vinyl ether-derived oxocarbenium ions are unexplored processes.…”

“…17a,23 All reported cases of bimolecular additions into oxocarbenium ions utilized either sterically hindered nucleophiles 22a or highly specific electrophiles. 17a,22g,23 Asymmetric Brønsted acid-catalyzed additions of silylated nucleophiles to vinyl ether-derived oxocarbenium ions are unexplored processes. The obstacle to these reactions lies in the need to regenerate the Brønsted acid when a silyl cation acts as the electrofuge.…”

“…Acetals are also suitable substrates for this process, yielding products with similar levels of enantiocontrol. These processes represent the first examples of asymmetric Brønsted acid-mediated addition reactions of silylated nucleophiles with vinyl ethers and acetals and are rare cases 17a,22a,22g23 in which enantioselectivity has been observed in bimolecular reactions into oxocarbenium ions. Computational studies suggest that the attraction in the ion pair arises from associations between the conjugate base of the catalyst with the electrophilic carbon and its attached hydrogen in the oxocarbenium ion.…”

From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

“…The BDE (bond dissociation energy) of the considered fragment needs to be low, and the positive charge obtained through oxidation needs to be stabilized. Oxidation of activated C–H bonds can be obtained by electrochemical methodologies,80 electron transfer,81 or by the use of stoichiometric oxidants 82. In the case of stoichiometric oxidants, there is clearly a low compatibility with the enamines generated in situ , as they could be oxidized 83.…”

“…Oxidation of activated C-H bonds can be obtained by electrochemical methodologies, [80] electron transfer, [81] or by the use of stoichiometric oxidants. [82] In the case of stoichiometric oxidants, there is clearly a low compatibility with the enamines generated in situ, as they could be oxidized. [83] MacMillan reported a beautiful and varied chemistry when enamines obtained in situ are treated with a strong oxidant, forming the corresponding radical cationic intermediates.…”