Three‐Component Coupling of Arynes and Organic Bromides

Abstract

Magic trio: Arynes are easily coupled with neutral nucleophiles and organic bromides to afford functionalized bromoarenes depending upon the nucleophile (Nu). The three‐component coupling proceeds through the formation of bromine ate complexes, and can be applied to the synthesis of multisubstituted isoquinolines and benzo[b]oxepines having pharmacological activity.

Experimental and mechanistic analysis of the palladium-catalyzed oxidative C8-selective C–H homocoupling of quinoline N-oxides

“…4c In addition, pyridine and 1,2,3-triazole N -oxides undergo oxidative C2–H and C5–H homocoupling reactions, respectively. 10 …”

4.09 Nucleophilic Coupling with Arynes

“…Isocyanide-derived zwitterion 82 can also be captured by alkynyl and perfluoroaryl bromides to give 84 and 85 (Scheme 73), 228 and the method allows the use of cyclic ethers including oxetanes and THF of less nucleophilicity, which are transformed into ring-opened products (Scheme 74). C-Br bond-and subsequent C-C bond-forming processes between carbanion 86 and nitrilium cation 87 (or oxonium cation 88) rationally explain the product formation (Scheme 75).…”

Bromopentafluorobenzene

“…However, Takaki and coworkers reported that a dipolar adduct of an isocyanide to a benzyne could abstract the bromine to produce a C 6 F 5 − anion that will add to the nitrilium to form an imine (eq 11). 15 Gevorgyan reported that an enolate can abstract Br + from C 6 F 5 Br to produce an α-bromoketone and a C 6 F 5 − anion. The nucleophilic addition of the latter at the carbonyl group generates an alkoxide, which, upon intramolecular S N 2 reaction, provides a C 6 F 5 -substituted epoxide (eq 12).…”