Selective arene functionalization through sequential oxidative and non-oxidative Heck reactions

Abstract

A sequence of acetamide directed oxidative Heck reaction and deacetylation-diazotation-Heck coupling allows the traceless removal of the acetamide group and its dual exploitation as a catalyst directing group and a leaving group.

Acetamidoarenediazonium Salts: Opportunities for Multiple Arene Functionali­zation

“…The acetamido group in p ‐ 27a was then exploited as a catalyst‐directing group in a Fujiwara–Moritani reaction77,78 under conditions previously reported by Youn and co‐workers79 and by ourselves,27 to give the substituted cinnamate 29 . As mentioned in the Introduction, we have recently developed protocols for deacetylation/diazotization/coupling (DDC) sequences that allow the dual exploitation of acetamides as a catalyst‐directing group and subsequently as a virtual leaving group in a Pd 0 ‐catalyzed C–C bond‐forming reaction 27,28. By subjecting 29 to the conditions of a DDC sequence, we were able to synthesize 30 with methyl acrylate as a coupling partner, as well as stilbene 31 with styrene (Scheme ).…”

“…Methyl ( E )‐3‐(4‐Acetamido‐1,1′‐biphenyl‐3‐yl)acrylate (29): 27 Biphenyl p ‐ 27a (211 mg, 1.00 mmol) was dissolved in a mixture of CH 2 Cl 2 (1 mL) and CF 3 CO 2 H (4 mL). K 2 S 2 O 8 (270 mg, 1.00 mmol) and Pd(OAc) 2 (11 mg, 5.0 mol‐%) were added, followed by methyl acrylate (172 mg, 2.00 mmol).…”

“…Dimethyl (2 E ,2′ E )‐3,3′‐(1,1′‐Biphenyl‐3,4‐diyl)diacrylate (30): 27 BF 3 · CH 3 OH (324 μL, 3.00 mmol) was added to a solution of p ‐ 27a (295 mg, 1.00 mmol) in anhydrous methanol (6.0 mL). The solution was heated to reflux for 16 h and then cooled to 0 °C, and tert ‐BuONO (120 μL, 1.00 mmol) was added.…”

“…Our main contribution to the field is the development of a deacetylation/diazotization (DD) sequence for the one‐flask synthesis of arenediazonium salts from acetanilides,21–25 and the extension of this synthesis through a Pd‐catalyzed coupling or cross‐coupling reaction to a deacetylation/diazotization/coupling (DDC) sequence 26. In previous contributions we demonstrated that DD and DDC sequences have the potential to broaden the scope and synthetic utility of oxidative Pd‐catalyzed C–H activation reactions of the Fujiwara–Moritani type, because they allow efficient recycling of the catalyst‐directing acetamido group by conversion into a diazonium leaving group 27,28…”

Amides as Weak Coordinating Groups in Proximal C–H Bond Activation

“…Elizarov and coworkers described new oxidative Heck reactions of anilides under Pd II catalysis conditions. They successfully synthesized ortho ‐dialkenylated benzenes through a deacetylation/diazotization/Heck coupling sequence (Scheme ) …”