Mizoroki–Heck Reactions with 4‐Phenoldiazonium Salts

Abstract

Significantly better yields were achieved in Mizoroki-Heck reactions using 4-phenoldiazonium salts instead of their O-alkylated analogues under otherwise identical conditions. We found that a oneflask deacetylation-diazotation-precipitation sequence starting from paracetamol or acetanilides derived thereof provides a convenient access to the required diazonium tetrafluoroborates. The utility of these arylating agents in palladium-catalyzed C À C bond forming reactions was demonstrated for a oneflask-synthesis of the heterocyclic core of the drug aripiprazole. Notably, the diazonium salt formation from an acetanilide could be combined with two Pdcatalyzed steps in a one-flask sequence, without any exchange of solvents or isolation of intermediates.

Pd‐Catalyzed [2+2+1] Coupling of Alkynes and Arenes: Phenol Diazonium Salts as Mechanistic Trapdoors

“…Phenol diazonium cation versus quinone diazide structure. [33] on 4 a and 69 % based on tolane (5 a). No other coupling products were detected, leading to the assumption that unreacted phenol diazonium salt undergoes hydrodediazonation to phenol.…”

“…In a first experiment (Table 1, entry 1), our optimized conditions for Heck reactions of alkenes were adopted, [33] that is, a 1:1 ratio of both reactants, excess NaOAc as a base, and 2.5 mol % of PdA C H T U N G T R E N N U N G (OAc) 2 as a precatalyst. A single product was isolated, which was identified as the spirocycle 6 aa.…”

“…We explored the scope of the Pd-catalyzed [2+2+1] cyclization for various 4-phenol diazonium salts 4 a-f [33] and alkynes 5 a-n. [52] To this end, the optimized conditions were applied, by using ligandless PdA C H T U N G T R E N N U N G (OAc) 2 (0.5 mol %) in the absence of a base in methanol. The results are summarized in Table 2: all substituted 4-phenol diazonium salts 4 b-f react under the standard conditions in good yields and with reasonably short reaction times with 5 a in the same [2+2+1] fashion found for the parent diazonium salt 4 a.…”

“…[42] We have recently discovered that phenol diazonium salts, such as 4 a, are remarkable arylating agents in Heck reactions. [33,34] In most cases, significantly better yields were obtained than with other arene diazonium salts and-rather unusual for diazonium salts-occasionally basic conditions are strongly preferred over base-free [43] conditions. 1 H-and 13 C NMR spectroscopic investigations revealed that, under the conditions used by us, a quinone diazide structure 4 a', resulting from deprotonation of 4 a, is involved to a significant extent (Scheme 5).…”

“…1 H-and 13 C NMR spectroscopic investigations revealed that, under the conditions used by us, a quinone diazide structure 4 a', resulting from deprotonation of 4 a, is involved to a significant extent (Scheme 5). [33] The oxidative addition of a diazonium cation 4 a to Pd 0 leads to a cationic Pd-s-aryl complex, which might undergo carbopalladation reactions of alkynes analogous to other Pd-s-aryl complexes. On the other hand, quinone diazides, such as 4 a', are carbene precursors, [44] which react with alkynes in a [2+1] or [2+2+1] fashion.…”