Nitriles Organozinc reagents

Organozinc reagent prepared from the 2-(trimethylsilyl)allyl bromide 156 and zinc react with alkynes or carbonyl compounds as well as nitriles to give the corresponding coupling products in moderate to good yields (equation 130)225. 

Michael reactions.1 Various organozinc reagents bearing remote ester, nitrile, or a-amino acid groups undergo Michael addition to a,(3-unsaturated carbonyl compounds in the presence of CuCN, (CH3)3SiCl, and HMPA.1... 

The organozinc reagents obtained by the same method from a-bromoesters react readily with the solvent CH3CN (Equation 8.13) or with a nitrile as... 

The electrosynthesis of /Miydroxy esters (220), 2,3-epoxy esters (221) and /Miydroxy nitriles (222) was achieved under nickel-catalyzed conditions, obviating Reformatsky reaction 70(equation 112-114). The reaction proceeds in excellent yield when a sacrificial zinc rod is used as the anode. A mechanism has been proposed which involves reduction of a Ni(II) complex to a Ni(0) complex, oxidative addition of the a-chloroester to the Ni(0) complex, and a zinc (II)/Ni(II) exchange, leading to an organozinc reagent, in analogy to the Reformatsky reactions. 

On the basis of this concept the same group has developed a similar strategy using a copper-catalyzed addition of organozinc reagents to enones, followed by trapping of the resulting zinc-enolate by ketones, esters or nitriles as terminal electrophiles (Scheme 35) [83]. 

Organozinc reagents are insuffieiently reactive to react with carbonyl derivatives and double bonds, exeept allyl and propargylzinc reagents that react with carbonyl derivatives, nitriles and alkynes. 

RCu(CN)ZnI.u These new copper reagents are prepared by reaction of primary or secondary iodides with zinc that has been activated with 1,2-dibromoethane and chlorotrimethylsilane. The resulting organozinc compounds are then allowed to react with the THF-soluble CuCN-2LiCl (equation I). Because of the mild conditions, these new reagents can be prepared from iodides containing keto, ester, and nitrile groups. 

The massive zinc (rod or plate) reacts spontaneously with activated bromides provided the preliminary electroreduction of a catalytic amount of zinc salt (ZnBr2 or ZnCl2) occurs. Reactions are carried out in nitrile solvents (CH3CN, PhCN,. ..) or their mixture with dichloromethane. An undivided cell fitted with a zinc anode and an indifferent cathode (gold, nickel, carbon, zinc,. ..) is used. As observed with benzylic bromides, the activation leads to an organozinc compound able to react with either the nitrile solvent or an electrophile reagent. The process is depicted in equation 12. 

Reformatsky first introduced electron-withdrawing substituents on the a-carbon of an organozinc halide, leading to the more reactive and thermally stable a-(alkoxycarbonyl)alkylzinc halides (123).107 Typically these reagents react with aldehydes or ketones to afford 3-hydroxy esters while nitriles afford 3-keto esters (Blaise reaction),l07b>c but 1,4-conjugate additions to select a,3 unsaturated ketones are precedented (Section 1.2.2.2.2). 

The application of functionally substituted organozincs allows for the construction of carbon-carbon bonds while circumventing tedious protection-deprotection strategies, as exemplified below.Note that tosyl cyanide reacts with alkenyl or arylzinc reagents to provide a,(3-unsaturated alkenyl or aromatic nitriles, respectively. 

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