Cross-dehydrogenative coupling of α-C(sp³)–H of ethers/alkanes with C(sp²)–H of heteroarenes under metal-free conditions

Abstract

Here we have developed an effective metal-free dehydrogenative coupling method wherein α-oxyalkyl and alkyl radicals were generated from various ethers and alkanes to undergo coupling with a variety of electron-deficient heteroarenes such as un/substituted iso-quinolones, quinolines, pyridines, pyrazines and pyrimidines. The persulfate-acetone-water system was optimized for the dehydrogenative coupling with cyclic ethers which gave moderate to excellent yields of α-oxyalkyl containing heteroarenes. We have also optimized the conditions for coupling with cyclic alkanes and alicyclic ethers and demonstrated by conducting the reactions with a variety of electron-deficient heteroarenes. Further, the present method is also applicable to electron deficient arenes like naphthoquinones and moreover, it didn't require any external acid.

Beyond Friedel and Crafts: Directed Alkylation of C−H Bonds in Arenes

“…[59] Substitution at the C2-position appears to be essential to avoid double alkylation. [61][62][63] The same oxidant could also be used to promote the direct alkylation of pyridine N-oxides with cyclic ethers by using copper(II) oxide as ac atalyst. [60] Thedirect alkylation of nonfunctionalized pyridines and related azines could also be promoted with cyclic and acyclice thers (as well as with some cyclic alkanes) by using K 2 S 2 O 8 as an oxidant.…”

“…[60] Thedirect alkylation of nonfunctionalized pyridines and related azines could also be promoted with cyclic and acyclice thers (as well as with some cyclic alkanes) by using K 2 S 2 O 8 as an oxidant. [61][62][63] The same oxidant could also be used to promote the direct alkylation of pyridine N-oxides with cyclic ethers by using copper(II) oxide as ac atalyst. [64] Ac ombination of (NH 4 ) 2 S 2 O 8 and N-hydroxysuccinimide was also shown to promote the cross-dehydrogenative coupling between cyclic ethers and N-heteroarenes in good yields.…”

Beyond Friedel and Crafts: Innate Alkylation of C−H Bonds in Arenes

“…When starting from N ‐iminopyridine ylides, 2‐alkylpyridine derivatives could be obtained by using simple alkanes or alcohols and benzoyl peroxide as the oxidant . The direct alkylation of nonfunctionalized pyridines and related azines could also be promoted with cyclic and acyclic ethers (as well as with some cyclic alkanes) by using K 2 S 2 O 8 as an oxidant . The same oxidant could also be used to promote the direct alkylation of pyridine N ‐oxides with cyclic ethers by using copper(II) oxide as a catalyst .…”

Jenseits von Friedel und Crafts: dirigierte Alkylierung von C‐H‐Bindungen in Arenen

“…[60] Die direkte Alkylierung nichtfunktionalisierter Pyridine und verwandter Azine konnte mit cyclischen und acyclischen Ethern (sowie einigen cyclischen Alkanen) mithilfe von K 2 S 2 O 8 als Oxidationsmittel ebenfalls gefçrdert werden. [61][62][63] Das gleiche Oxidationsmittel konnte auch zur Fçrderung der direkten Alkylierung von Pyridin-N-oxiden mit cyclischen Ethern mithilfe von Kupfer-(II)-oxid als Katalysator eingesetzt werden. [64] Eine Kombination aus (NH 4 ) 2 S 2 O 8 und N-Hydroxysuccinimid fçrderte in guten Ausbeuten die dehydrierende Kreuzkupplung zwischen cyclischen Ethern und N-Heteroarenen.…”