Aryl cyanides synthesis

MILLER-SNYDER Aryl Cyanide Synthesis Synthesis of benzonitriles from aldehydes via oxime ethers in the presence of p-nitrobenzonitrile. Formation of p-cyanophenol fron p-nitrobenzaldoxime and p-nitrobenzonitrile (used as a sometimes recyclable chain carrier) (see 1st edition). 

The synthesis of (hetero)aryl cyanides from (hetero)aryl halides via transition-metal catalysis is a very valuable reaction since a nitrile can be easily transformed into several other functional groups. Not until 2000 were the first examples on microwave-assisted cyanation reported in the literature. Alter-man and Hallberg found that 3-bromopyridine and 3-bromothiophene were... 

Me3SiCN is a convenient, reactive cyanide donor in transition metal-catalyzed processes. The Pd-catalyzed reaction of aryl iodides with Me3SiCN is useful for the synthesis of aryl cyanides.257 Me3SiCN works also as an effective co-catalyst for the Pd-catalyzed cyanation of aryl iodides with KCN.258 Allylic acetates, carbonates, and the related compounds undergo the Pd-catalyzed cyanation with Me3SiCN.259-261 The tandem cyclization-cyanation reaction of 2-bromo-l,6-heptadienes with Me3SiCN proceeds under catalysis by an Ni complex (Equation (68)).262... 

Sandmeyet reaction, synthesis, of aryl cyanides, 594 of aryl halides, 94 Schiemann reaction, 95 Schiff bases, see also Imines... 

Some orientation control has been achieved in electrophilic aromatic substitution reactions effected with thallium (III) trifluoroacetate, and methods for synthesis of aryl cyanides and phenols using this useful reagent have been developed, "... 

S. Sipos, I. Jablonkai, Tetrahedron Lett. 2009, 50, 1844-1846. One-pot synthesis of a-aminonitriles from alkyl and aryl cyanides a Strecker reaction via aldimine alanes. 

Enantioselective Synthesis of (—)-Esermethole via Asymmetric Alkene Insertion into a C-C Bond of Aryl Cyanides... 

In 2011, Nakai et al. found that acyclic compounds also participated in cycloaddition through carbon-carbon bond activation (Scheme 12.22). Reaction of o-arylcarboxybenzonitrile 56 and 4-octyne in the presence of a nickel catalyst, prepared in situ from Ni(cod)2 and PMes, and MAD in toluene at 120 °C for 12 h resulted in the formation of coumarin 58 in 80% yield. Sequential inter- and intramolecular carbon-carbon cleavage in the presence of a nickel catalyst has been used to construct flve-membered oxanickelacycle 57, which reacts with alkynes to furnish cycloadducts [27]. Detailed observations revealed that the catalytic reaction proceeded with the elimination of aryl cyanide. A similar sequence has been utilized for the synthesis of quinolone derivative 59 (Scheme 12.23). These reaction outcomes suggest an unusual mechanistic aspect cleavage of two independent C—CN and C—CO bonds via the formation of a heteronickelacycle intermediate. 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of halides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsiiyl cyanide in EtiN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

A short synthesis of 6-cyano-l,2,3,4-tetrahydroisoquinoline used an improved method of aryl triflate cyanation that employs zincfll) cyanide as the cyanide source <95SC(25)3255>. 

Catalytic asymmetric cyanide addition to imines constitutes an important C—C bondforming reaction, as the product amino nitriles may be converted to non-proteogenic a-amino acids. Kobayashi and co-workers have developed two different versions of the Zr-catalyzed amino nitrile synthesis [73]. The first variant is summarized in Scheme 6.22. The bimetallic complex 65, formed from two molecules of 6-Br-binol and one molecule of 2-Br-binol in the presence of two molecules of Zr(OtBu)4 and N-methylimidazole, was proposed as the active catalytic species. This hypothesis was based on various NMR studies more rigorous kinetic data are not as yet available. Nonetheless, as depicted in Scheme 6.22, reaction of o-hydroxyl imine 66 with 5 mol% 65 and 1—1.5 equiv. Bu3SnCN (CH2C12, —45 °C) leads to the formation of amino nitrile 67 with 91 % ee and in 92 % isolated yield. As is also shown in Scheme 6.22, electron-withdrawing (— 68) and electron-rich (—> 69), as well as more sterically hindered aryl substituents (— 70) readily undergo asymmetric cyanide addition. 

In the unconventional synthesis of thioethers (Scheme 4.11), cyanide ion is displaced from thiocyanates by carbanions [52, 53], which have been generated under phase-transfer catalytic conditions (cf. 4.1.12). Thiocyanates are readily obtained by a standard catalysed nucleophilic substitution reaction [4, 54-58] (see Table 4.19). Aryl thiocyanates are obtained from activated aryl halides [4, 57] (see Chapter 2). 

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