The Cyanation of Aromatic Halides Catalyzed by Nickel(0) Complexes Generated In Situ. I. General Scope and Limitations

Abstract

The cyanation of chlorobenzene catalyzed by Ni(PPh3)n, which was generated in situ from NiBr2(PPh3)2–Zn–PPh3(Ni : Zn : P=1 : 3 : 2 molar ratio), was at first examined with various MCN (M=K, Na)–solvent systems by three procedures in order to clarify the conditions under which the reaction occurs. The effects of the systems and the procedures on the reaction were remarkable. It was observed that the cyanide ion has an inhibitory action on both the reduction of Ni(II) and the oxidative addition of the halide to Ni(0). However, when such MCN–dipolar aprotic solvent systems as KCN–HMPA, KCN or NaCN–MeCN, which give low cyanide concentrations, were used, the reaction readily took place at 50–60 °C without reducing Ni(II) prior to the addition of MCN and adding MCN slowly. Various Y-substituted chlorobenzenes, except for those with Y=o-Cl, o-CN, and m-NO2, were cyanated to give the corresponding nitriles in fair to good yields. NiBr2–PPh3 can be used in place of NiBr2(PPh3)2 if MCN is added after reduction. In addition, less reactive halides, such as o-dichlorobenzene and o-chlorobenzonitrile, were fairly smoothly cyanated by the use of NiBr2–1,1′-bis(diphenylphosphino)ferrocene.

Mild and Efficient Copper‐Catalyzed Cyanation of Aryl Iodides and Bromides

“…In the case of 3‐nitrobromobenzene (Table 1, entry 5), small amounts of hydrodehalogenation (C 6 H 5 NO 2 ) and nitro‐reduction (BrC 6 H 4 NH 2 ) products were detected but the selectivity of 88 % remains acceptable. Our copper‐based catalytic system is therefore compatible with the nitro substituent, whereas nickel‐catalyzed cyanation of nitro‐substituted aryl halides failed 9a. Note that the presence of an amino substituent also allows the synthesis of the corresponding nitrile in a very good yield and with excellent selectivity (>99 %) (Table 1, entry 4).…”

Increasing the Scope of Palladium‐Catalyzed Cyanations of Aryl Chlorides

“…Sakakibara et al have reported about nickel-based cyanation reactions, unfortunately HMPA was found as the best solvent. [10] More recently, we reported the use of PdA C H T U N G T R E N N U N G (OAc) 2 /n-butyl-di(1-adamantyl)phosphine (Scheme 2, ligand 1) for reactions of aryl chlorides with non-reactive substituents. [11] Most currently, Littke and coworkers described the use of 4 mol% Pd and 8 mol% of a special Buchwald-type ligand (Scheme 2, ligand 2), Zn as additive, and Zn(CN) 2 as cyanide source.…”

The synthesis of carbon-14 labeled (R)-4-(dipropylamino)-1,3,4,5-tetrahydrobenz[cd]indole-6-carboxamide hippurate. A partial ergoline with 5-HT1A agonist activity and an125I-labeled analog

“…Reaction of 3a (Scheme 1) with NaCN/Pd(Ph 3 P) 4 2 /Zn/Ph 3 P in lower boiling solvents (THF or CH 3 CN). 9 In our hands, the best results in the reaction of 2 with NiBr 2 (Ph 3 P) 2 /Zn/Ph 3 P to yield 5a were obtained using CH 3 CN as the solvent (Scheme 2). Reaction of 2 with K 14 CN in the presence of NiBr 2 (Ph 3 P) 2 / Zn/Ph 3 P in refluxing acetonitrile gave 5b in 51% yield.…”