A J-Unsaturated nitriles

Z)-x,p- Unsaturated nitriles.2 The lithio derivative of 1 reacts with aldehydes to form a mixture of (Z)- and (E)-a,/J-unsaturated nitriles with some preference for the former isomer. The stereoselectivity in favor of the (Z)-isomer in reactions with aliphatic aldehydes is markedly improved by use of the boron derivative, obtained by treatment of the lithium reagent with boron isopropoxide. Addition of HMPT also favors the (Z)-isomer. 

The problems are due to the electrophilicity of the metal-carbene intermediates in these transformations, and to competitive, fast dihydropyrazole formation resulting from uncatalyzed thermal [3 + 2] cycloaddition of the diazo compound to the alkene furthermore, a,/J-unsaturated nitriles often yield 2-vinyloxazoles under the reaction conditions. 

CONJUGATE ADDITION TO a,/J-UNSATURATED NITRILES, CARBOXYLIC ACIDS AND DERIVATIVES... 

Synthesis via combining alkylpyridazinylcarbonitrile with a,J -unsaturated nitriles... 

Phosphonate carbanions, formed by percolation of a dilute ether solution of the diethyl phos-phonate through a macroporous AER in HO" form, react with carbonyl compounds in Horner-Wittig syntheses of alkenes (Scheme 20). " a,j -Unsaturated nitriles are formed from both aldehydes and ketones, but a,) -unsaturated esters are formed only from aldehydes. The reactions... 

In contrast to the related organoboranes, which are mostly used in the addition to non-polar carbon-carbon multiple bonds, aluminum hydrides have found their widest use in organic synthesis in the addition reaction to polar carbon-carbon and carbon-heteroatom multiple bonds including carbonyl, nitrile and imino groups as well as their a,(J-unsaturated analogs. Although these reduction reactions are also sometimes referred as hydroalumination reactions in the Hterature, they are outside the scope of this review. 

In a,(J-unsaturated ketones, nitriles, and esters (e.g., 119), the y hydrogen assumes the acidity normally held by the position a to the carbonyl group, especially when R is not... 

Cyclopropane formation occurs from reactions between diazo compounds and alkenes, catalyzed by a wide variety of transition-metal compounds [7-9], that involve the addition of a carbene entity to a C-C double bond. This transformation is stereospecific and generally occurs with electron-rich alkenes, including substituted olefins, dienes, and vinyl ethers, but not a,(J-unsaturated carbonyl compounds or nitriles [23,24], Relative reactivities portray a highly electrophilic intermediate and an early transition state for cyclopropanation reactions [15,25], accounting in part for the relative difficulty in controlling selectivity. For intermolecular reactions, the formation of geometrical isomers, regioisomers from reactions with dienes, and enantiomers must all be taken into account. 

Various activated olefins can also be employed instead of organic halide for the formation of a carbon-silicon bond. Thus, cathodic reduction of a,j -unsaturated esters, nitriles... 

In the cycloaddition of triisopropylallylsilane to a, /J-unsaturated lactams 197, cyclobutane adducts 198 have been found to be the kinetic products whereas the formation of cyclopentanes 199 is thermodynamically controlled285. Reactions of allenylmethylsilanes with activated unsaturated esters and nitriles (equation 163)286 and allylsilanes with unsaturated esters287 are other examples of using [2+2] cycloaddition to construct cyclobutane derivatives. 

The third variant employed an ce./J-unsaturated nitrile as electrophile1078. The addition of compound 740 to a-methylcinnamonitrile at — 78 °C led to the formation of a... 

Hetero-Diels-Alder reactions performed with trifluoromethyl-substituted heterodienes or with trifluoromcthyl-substituted heterodienophiles have resulted in the synthesis of a large number of fluoro-heterocyclic compounds. Ketones, thioketones, imincs, nitriles, and their parent a./J-unsaturated systems have been studied in cycloaddition reactions. Cycloadditions are regioselec-tive. An interesting aspect is the competition with ene-type reactions, aldol reactions and. depending on the partners, with [2 + 2]-cycloaddition reactions. 

As olefinic substrates a,j -unsaturated carbonyl compounds (esters, anhydrides, ketones, quinones), nitriles and nitro compounds can be used. The rate of addition of the diazo compounds is dependent upon the nature of the diazo compound and generally the following order of reactivity can be observed diazomethane > diphenyldiazomethane > methyl diazoacetate > diazoketones. 

The reaction between a,/ -unsaturated nitriles and Grignard reagents was studied in a few cases [4]. With a,j -ethylenic nitriles, saturated [4,34-36] and vinylic [37] Grignard reagents lead to 1,4-addition products ... 

Carboxylic amides. Gilman2 has extended the procedure of Corey et al. (2, 261) for oxidation of allylic alcohols to carboxylic esters to the preparation of carboxylic amides. Thus oxidation of aromatic and a,/J-unsaturated aldehydes with Mn02 in the presence of sodium cyanide and an amine gives the corresponding carboxylic amides in high yield. In the absence of sodium cyanide, high yields of nitriles are formed from aldehydes, ammonia, and manganese dioxide. 

Xu, Z.-Q., and DesMarteau, D.D., A convenient one-pot synthesis of a-fluoro-a,P-unsaturated nitriles from diethyl cyanofluoromethanephosphonate, J. Chem. Soc., Perkin Trans. I, 313, 1992. 

Zhang, T.Y., O Toole, J.C., and Dunigan, J.M., An efficient and practical synthesis of diphenyl cyanomethylenephosphonate. Applications to the stereoselective synthesis of crT-a,P-unsaturated nitriles. Tetrahedron Lett., 39, 1461, 1998. 

Etemad-Moghadam, G., and Seyden-Penne, J., Highly stereoselective synthesis of -a,P-unsaturated nitriles from diphenyl cyanomethyl phosphine oxide, Synth. Commun., 14, 565, 1984. 

The reaction of Michael acceptors with dimethyloxosulfonium methanide has been extensively explored.3 4,111 112 115 In addition to carbene (or carbenoid) additions (Section 1.2.1.) and the Simmons-Smith method,114 (see also Section 1.2.1.1,) this is the most widely utilized method for the introduction of a cyclopropane ring, in good to excellent yield, to a,/J-unsaturated ketones,120- 126 esters118 120,122,128 - 130,132 amides,118,119 133 nitriles,1l8-119,126 isonit-... 

Carbonylation of [CoH(CN)j] in strongly alkaline media results in the formation of [Co(CN)j-(00)2] and the intermediacy of the short-lived tetracyanocobaltate(I) ion [Co(CN)4] in this process has been inferred from mechanistic studies (Scheme 9). Under very similar conditions [CoH(CN)5] " catalyzes the cyanation of vinyl halides to form a,/S-unsaturated nitriles with retention of configuration (equation 6). Oxidative addition of vinyl halide to the intermediate [Co(CN)4] " ion is stereoselective and in the a complex so produced reductive coupling of the vinyl and cyano ligands gives the stereoretentive organic product and regenerates [Co(CN)4] . ... 

In 1989, Isayama and Mukaiyama reported a related Co-catalyzed coupling reaction that employs a,b-unsaturated nitriles, amides, and esters with PhSiHs as a hydrogen source [9]. Cobalt-bis(diketonato) complex, Co(II)(dpm)2 [dpm = bis(dipivaloylmethanato)] (5mol%), exhibited high catalytic activity at 20 °C in the coupling of excess acrylonitrile and ben-zaldehyde to provide b-hydroxy nitrile 4 in 93% yield (syn anti = 50 50) (Scheme 5). N,J -Dimethylacrylamide and methyl cinnamate both reacted... 

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