Silver-catalyzed remote Csp3-H functionalization of aliphatic alcohols

Abstract

Aliphatic alcohols are common and bulk chemicals in organic synthesis. The site-selective functionalization of non-activated aliphatic alcohols is attractive but challenging. Herein, we report a silver-catalyzed δ-selective Csp3-H bond functionalization of abundant and inexpensive aliphatic alcohols. Valuable oximonitrile substituted alcohols are easily obtained by using well-designed sulphonyl reagents under simple and mild conditions. This protocol realizes the challenging δ-selective C–C bond formation of simple alkanols.

Silver-Mediated Methoxylation of Aryl C(sp2)–H Bonds Directing by DMEDA

“…While this transformation is a cross-dehydrogenative coupling (CDC) reaction, high-valent metal is needed for the electrophilic activation of C(sp 2 )-H bonds [34][35][36][37]. Since high-valent silver is rare in relation to copper under normal conditions, [38] the combination of Ag(I) and K 2 S 2 O 8 which proved to be efficient for a silver-catalyzed or silver-mediated system was used in this system [31,32]. However, no good result was observed after the preliminary screening.…”

“…However, all of these reactions were carried out with silver reagents. While silver is also a common transition metal catalyst for C-H functionalization [26][27][28][29][30][31][32], silver-mediated alkoxylation of aryl C(sp 2 )-H bonds will be attractive but challenging.…”

Catalytic generation of alkoxy radicals from unfunctionalized alcohols

“…61 Silver catalysis was again leveraged for alkoxy radical formation in a report by the Jiao group in 2018, this time to promote 1,5-HAT and subsequent C(sp 3 )-H bond functionalization to form oxime ether products. 62 The authors identify AgNO 3 and K 2 S 2 O 8 as the optimal metal/oxidant pair to use for selective d-C-H abstraction and a sulfonyl oxime ether reagent as the radical acceptor for the transformation (Scheme 15). The reaction tolerates primary and secondary alcohols, including substrates bearing halogen and azide substituents.…”

Diverse strategies for transition metal catalyzed distal C(sp3)–H functionalizations

“…74 In 2018, Jiao group reported an elegant Ag catalyzed protocol for selective d-functionalization of aliphatic alcohols. 75 Generating alkoxy radicals from free alcohol via O-H bond hemolytic cleavage is extremely challenging due to its bond energy. AgNO 3 was successfully utilized to generate alkoxy radical along with K 2 S 2 O 8 as the oxidant.…”