3,3-Disubstituted acrylonitriles, reaction with

In the preparative application of [2 + 2]-photocycloadditions of cyclic enones to (substituted) alkenes, two factors concerning product formation are of decisive relevance, namely the regioselectivity and the (overall) rate of conversion. Regarding the regioselectivity in the addition to mono- and 1,1-disubstituted alkenes, Corey had shown that the preferred addition mode of cyclohex-2-enone to isobutene or 1,1-dimethoxyethylene was the one leading to—both cis- and trans-fused—bicyclo[4.2.0]octan-2-ones with the substituents on C(7) [8]. In contrast, in the reaction with acrylonitrile, the alternate orientation was observed to occur preferentially. Similar results were also reported by Cantrell for the photocycloaddition of 3-methyl-cyclohex-2-enone to differently substituted alkenes [14]. No significant differences in the overall rates of product formation for the different alkenes were observed in these studies. In order to explain these observed... 

This regioselectivity is practically not influenced by the nature of subsituent R. 3,5-Disubstituted isoxazolines are the sole or main products in [3 + 2] cycloaddition reactions of nitrile oxides with various monosubstituted ethylenes such as allylbenzene (99), methyl acrylate (105), acrylonitrile (105, 168), vinyl acetate (168) and diethyl vinylphosphonate (169). This is also the case for phenyl vinyl selenide (170), though subsequent oxidation—elimination leads to 3-substituted isoxazoles in a one-pot, two-step transformation. 1,1-Disubstituted ethylenes such as 2-methylene-1 -phenyl-1,3-butanedione, 2-methylene-1,3-diphenyl- 1,3-propa-nedione, 2-methylene-3-oxo-3-phenylpropanoates (171), 2-methylene-1,3-dichlo-ropropane, 2-methylenepropane-l,3-diol (172) and l,l-bis(diethoxyphosphoryl) ethylene (173) give the corresponding 3-R-5,5-disubstituted 4,5-dihydrooxazoles. 

Cyanoethyl derivatives can be prepared with acrylonitrile. Both mono-and disubstituted amino groups can be produced. Reaction at pH 9.2, 2°, with 0.4 M acrylonitrile for 7 days modified all lysine residues with no apparent change in any of the other amino acids (106). The lysine was almost entirely accounted for as dicarboxyethyllysine in acid hydrolysates of the derivative. The a-amino group had apparently also reacted. The fully substituted derivative had no RNA activity. The physical properties were very similar to those of native RNase-A. 

Further reaction of the bromide 33 with acrylonitrile in the presence of PI13P affords the disubstituted product 34 [21]. Selection of amines used in the reaction is critical. Fumaroyl dichloride (35) undergoes oxidative addition, decarbonylation and insertion of acrylate to produce octatrienedioate (36) [22]. 

Similarly, the enamine of a 2-substituted cyclohexanone is alkylated by electrophilic alkenes such as acrylonitrile or methyl acrylate at the exposition in methanol or acetonitrile. However, prolonged reaction time (66 h) of the pyrrolidine enamine of 2-methylcyclohexanone with these reagents in dioxane or benzene under reflux gives a 1 1 mixture of 2,2- and 2,6-disubstituted cyclohexanones (38 and 39)82>83 (Scheme 23). 

The complexes [Ni(acrylonitrile)2] and [Ni(COD)2] catalyze [3 + 2] cycloadditions of (26) with electron deficient l,2 isubstituted alkenes to afford 2,3- or 3,4-disubstituted methylenecyclopentanes such as (32) and (33). Similar reactions have been reported by use of tertiary phosphine complexes of nickel(0) and palladium(0) (equation 13 and Table 1). The reaction proceeds regioselectively to give (32) or (33) depending on both the alkene stmcture and catalytic system. Reactions catalyzed by phos-phine-palladium(0) complexes afford only products of the type (32), via selective cleavage of the C(2)— C(3)bondof(26). 

Diels-Alder reactions of l-methyl-2-(lH)-pyridinone (66) with maleic anhydride [71,72,73] and fumaronitrile [74] produced 2,6-disubstituted lactam-ISQs. Reaction of 66 with methyl acrylate and acrylonitrile yielded monosubstituted ISQ derivatives (67-68) in 23-30% overall yield (Scheme 5) [75]. 

The rates of radical-monomer reactions are also dependent on considerations of steric effects. It is observed that most common 1,1-disubstituted monomers — for example, isobutylene, methyl methacrylate and methacrylo-nitrile—react quite readily in both homo- and copolymerizations. On the other hand, 1,2-disubstituted vinyl monomers exhibit a reluctance to ho-mopolymerize, but they do, however, add quite readily to monosubstituted, and perhaps 1,1-disubstituted monomers. A well-known example is styrene (Ml) and maleic anhydride (M2), which copolymerize with r — 0.01 and T2 = 0 at 60°C, forming a 50/50 alternating copolymer over a wide range of monomer feed compositions. This behavior seems to be a consequence of steric hindrance. Calculation of A i2 values for the reactions of various chloroethylenes with radicals of monosubstituted monomers such as styrene, acrylonitrile, and vinyl acetate shows that the effect of a second substituent on monomer reactivity is approximately additive when both substituents are in the 1- or cr-position, but a second substituent when in the 2- or /3-position of the monomer results in a decrease in reactivity due to steric hindrance between it and the polymer radical to which it is adding. 

Aminoethylations with ethylenimine250 and Michael reactions have also demonstrated a preference for the acidic imide function. Thus the N3—H group adds to acetylene to give JV-3-vinylhydantoins251 and to activated ethylenes, such as acrylonitrile or 4-vinylpyridine, to give N-3-substituted hydantoins.25 252 253 Under some conditions 1,3-disubstituted hydantoins are obtained.251... 

Free-radical polymerization reactions have recently been studied for different monomers, for example mono and disubstituted vinyl monomers and dienes. The bulk polymerization of vinyl monomers (e.g. vinyl acetate, styrene, methyl methacrylate, and acrylonitrile) has been investigated by Amorim et al. [10]. The reactions were conducted in the presence of catalytic amounts of AIBN (or benzoyl peroxide). It was found that the rate of polymerization depends on the structure of the monomers and the power and time of microwave irradiation. In a typical experiment 10.0 mL of each monomer and 50 mg AIBN was irradiated in a domestic microwave oven for 1 to 20 min to afford the polymers polystyrene, poly(vinyl acetate), and poly(methyl methacrylate) with weight-average molecular weights 48 400, 150 200, 176700 g mol, respectively (Scheme 14.1). The experiments were performed without temperature control. 

Similarly, , -l,4-dimethylbutadiene reacts readily with many dienophiles, but the Z,E-isomer yields an adduct only when the components are heated in benzene at 150°C. Z,Z-l,4-Disubstituted butadienes are uiureactive. 1,1-Disubstituted butadienes also react with difficulty, and with such compounds addition may be preceded by isomerization of the diene to a more reactive species. Thus, in the reaction of 1,1-dimethylbutadiene with acrylonitrile, the diene first isomerizes to 1,3-dimethylbutadiene, which then reacts in the normal way. 

The order of reactivity of the alkenes is monosubstituted > disubstituted tri- and tetrasubstituted.f " Tri- and tetrasubstituted alkenes do not normally undergo inter-molecular arylations. The product pattern after arylations of 1,2-disubstituted alkenes is governed by both steric and electronic factors. Arylation of alkenes with one electron-withdrawing group is the most common Heck reaction. The reaction delivers /3-arylated products often in high yields. The ( )-isomers are most often formed but with some alkenes, for example, acrylonitrile, mixtures of the ( )- and (Z)-isomers are obtained. 

Af-Heterocydic carbene and phosphine systems were compared, and in some cases the bis-phosphine copper complex [Cu(NHPh)(dtbpe)] (dtbpe= l,2-bis(di-tert-butylphosphino)ethane) outperformed the NHC-based systems. Indeed, the transformation of aniline with acrylonitrile reached 95% conversion after 3h with dtbpe, whereas 12 h were required with [Cu(NHPh)(IPr)]. However, for the reaction of disubstituted cyclohexenone with aniline, [Cu(NHPh)(IPr)] outshone... 

The Ni -catalysed (2+2) cycloaddition of activated olefins such as acrylonitrile or acrylic acid esters to quadricyclane which gives endo- and exo-substituted products is complicated particularly in the case of 1,2-disubstituted olefins by a competing isomerization of quadricyclane to norbornadiene. Norbomadiene gives identical cycloadducts under these conditions with a similar isomer ratio. Kinetic studies of the cycloaddition reactions of quadricyclane gave a plot of log [quadricyclane]t o/ [quadricyclane]i=t against time which exhibited a marked deviation from linearity due to the retarding effect of norbomadiene which is also formed and in turn coordinates to the Ni catalyst. Scheme 11 accounts for these observations. 

Aza-MBH reaction between acrylonitrile (30) and imines (29) has been achieved with 98% ee using chiral phebim/Pd(II) complexes (32) to form a-methylene- -aminonitriles (31). Aza-MBH reactions of ArCH=NTs with electronically and 0 sterically deactivated Michael acceptors can be achieved by the use of electron-rich phosphanes (PArg) and pyridines (33) as catalysts (Scheme 21) Nucleophilic and steric influences, respectively, are exerted by new multifunctional chiral phosphines and BINOL derivatives used to cocatalyse aza-MBH reactions of 5,5-disubstituted cyclopent-2-enone and RCH=NTs in THF, with 99% yield and 85% ee ... 

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