Synthesis of Non‐Symmetric Azoarenes by Palladium‐Catalyzed Cross‐Coupling of Silicon‐Masked Diazenyl Anions and (Hetero)Aryl Halides

Abstract

The photoswitchable motif of azobenzenes is of great importance across the life and materials sciences. This maintains a constant demand for their efficient synthesis, especially that of non-symmetric derivatives. We disclose here a general strategy for their synthesis through an unprecedented C(sp 2 )À N(sp 2 ) cross-coupling where functionalized aryl-substituted diazenes masked with a silyl group are employed as diazenyl pronucleophiles. These equivalents of fragile diazenyl anions couple with a diverse set of (hetero)aryl bromides under palladium catalysis with no loss of dinitrogen. The competing denitrogenative biaryl formation is fully suppressed. The reaction requires only a minimal excess, that is 1.2 equivalents, of the diazenyl component. By this, a broad range of azoarenes decorated with two electron-rich/deficient aryl groups can be accessed in a predictable way with superb functional-group tolerance.

Palladium-Catalyzed Denitrogenative Cross-Coupling of Silicon-Masked, Aryl-Substituted Diazenes and Aryl Bromides

“…As part of our earlier screening of palladium catalysts, 8 we had identified Organ’s precatalyst Pd-PEPPSI- i -Pr 13 as suitable for the selective C(sp 2 )–C(sp 2 ) cross-coupling of the para -tolyl-substituted aryl pronucleophile 1a and the electron-rich electrophile 2a (Table 1 ). Under the reaction conditions previously established for the construction of azoarenes, 8 the biaryl 7aa was formed selectively, yet in 38% yield after a prolonged reaction time (entry 1); increasing the catalyst loading from 2.0 to 4.0 mol% resulted in an improved yield (entry 2). We then turned our attention towards the effect of the base on the coupling (entries 3–5).…”

“…5 6 Our laboratory recently disclosed an unprecedented way to the formation of non-symmetric azobenzene derivatives through a chemoselective C(sp 2 )–N(sp 2 ) cross-coupling of diazenyl anion equivalents and (hetero)aryl electrophiles under palladium catalysis (Scheme 1 , top). 7 8 Loss of dinitrogen to form the corresponding biaryl is a competing reaction channel (Scheme 1 , bottom), 9 10 11 and it is primarily the ligand in the palladium catalyst that determines the reaction outcome. The use of dppf with a wide bite angle facilitates reductive elimination, 12 thereby favoring the upper pathway.…”

“…The N -aryl- N ′-silyldiazenes were prepared according to previously reported procedures and stored in a glovebox. 7 8 3-Methoxyphenyl trifluoromethanesulfonate ( 3a ) and 3-methoxyphenyl 4-methylbenzenesulfonate ( 4a ) were synthesized according to a reported procedure. 14 Toluene was dried over Na, distilled under N 2 atmosphere, degassed by the freeze-pump-thaw method, and stored in a glovebox over thermally activated 4 Å molecular sieves.…”

Hydrazine–Halogen Exchange Strategy Toward N═N-Containing Compounds and Process Tracking for Mechanistic Insight

“…In recent years, CN coupling of protected hydrazine has emerged as a promising method for preparing ABs − and cinnolines; − however, they suffer from inevitable extra steps for protection as well as deprotection, leading to low step economy and efficiency. Direct use of N 2 H 4 ·H 2 O as a N 2 source to assemble NN compounds is a green and efficient way but has not been reported.…”

Synthesis of Benzhydryl-Substituted Amines by Silanolate-Mediated Aldimine Arylation with Functionalized Aryl Nucleophiles Released from Diazene-Based Reagents

“…Changing the countercation or using to tert-butoxide as another alkoxide Lewis base resulted in dramatically diminished yields or no reaction (entries 3−6). Fluoride as an initiatior that had enabled nucleophilic aromatic substitution of polyfluorinated arenes 16 was also inferior to Me 3 SiOK (entry 7). Likely as a result of the poor solubility of Me 3 SiOK in tetrahydrofuran (THF) 20 the yield of compound 4aa increased to 65% at higher dilution (entry 8 versus entry 2).…”