Methyl acrylate regioselectivity

A C-H activating Pd-catalyzed alkenylation of indole is regiospecific for 2-substitution when the nitrogen carries a 2-pyridylmethyl substituent (Equation 169) <2005CC1854>. Under the same conditions A -Bn-indole reacted with methyl acrylate regioselectively to afford 3-isomers in 95% yield. 

Table 6.15 Regioselectivity of Diels-Alder reactions of methyl acrylate with 2-substituted-l,3-butadienes in sc- CO2 and PhMe...

Treatment of 71a with phosphorus oxychloride readily afforded the dichloro derivative 79 in 95% yield. Michael addition with methyl acrylate in the presence of Triton B led to the regioselective formation of 80 (Scheme 3)... 

Alkylation of 72 with ethyl bromoacetate using K2C03 as the base resulted in the O-, N-dialkylated derivative 105, whereas regioselective mono N-alkylation took place with ethyl iodide in the presence of NaH to give 106. Moreover, 72 smoothly added to methyl acrylate to give 107 (Scheme 7) <2003JHC789>. 

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. 

The theoretical interpretation of the results was made (334) in terms of the molecular orbital perturbation theory, in particular, of the FMO theory (CNDO-2 method), using the model of the concerted formation of both new bonds through the cyclic transition state. In this study, the authors provided an explanation for the regioselectivity of the process and obtained a series of comparative reactivities of dipolarophiles (methyl acrylate > styrene), which is in agreement with the experimental data. However, in spite of similar tendencies, the experimental series of comparative reactivities of nitronates (249) toward methyl acrylate (250a) and styrene (250b) are not consistent with the calculated series (see Chart 3.17). This is attributed to the fact that calculation methods are insufficiently correct and the... 

Relatively polar diphosphine 8 has an elongated P-P bond, and thus exhibits unusual reactivity. The reaction of 8 with acrylonitrile or methyl acrylate proceeds at 50 °C in a chemo- and regioselective manner to afford the 1,2-addition product with the PPh2 group attached at the terminal position (Equation (64)).165 Tetrachlorodiphosphine reacts with cyclohexene to give trans-adduct presumably via an ionic pathway.166... 

Diels—Alder reactivity was also reported for a cationic zirconocene alkoxide (A Scheme 8.46) at a 10 mol% level for the substrate combination methyl acrylate/isoprene [84]. Whereas the regioselectivity (para/meta = 96.2 3.8) in this process compared favorably to that with traditional Lewis acids (A1C13 in C6H6 regioselectivity = 95 5), the activity was quite low. The substrates methyl acrylate and cydopentadiene (Scheme 8.46 R =... 

Titanium ylides are generated from imine esters with titanium isopropoxide chlorides and amines or by transmetalation of the N-lithiated ylides (90,91). The regioselectivity of their reactions with methyl acrylate is opposite to that normally observed (90). A transition state is proposed in Scheme 11.13 to explain this alternative regioselectivity. Intramolecular cycloadditions of the titanium ylides offer a synthetic application of this regioselectivity. 

Rates of radical additions to alkenes are controlled mainly by the enthalpy of the reaction, which is the origin of regioselectivity in additions to unsymmetrical systems, with polar effects superimposed when there is a favorable match between the electrophilic or nucleophilic character of the radical and that of the radico-phile. For example, in the addition of an alkyl radical to methyl acrylate (2), the nucleophilic alkyl radical interacts favorably with the resonance structure 3. Polar effects are apparent in the representative rate constants shown in Figure 4.14 for additions of carbon radicals to terminal alkenes. Addition of the electron-deficient or electrophilic rert-butoxycarbonylmethyl radical to the electron-deficient molecule methyl acrylate is 10 times as fast as addition of... 

Inductive effects exerted by substituents on the nitrile ylide also have an important effect on the regio-selectivity of the cycloaddition. Benzonitriliohexafluoro-2-propanide (73) and methyl acrylate yield products with inverse regioselectivity, as compared with the reactions of the related benzonitrilio-2-pro-panide (76 Scheme 18).83 The difference in regioselectivity has been attributed to the larger coefficient... 

Similarly, nitrile oxides react with methyl acrylate 2.42 to give the adduct 2.43 with the substituent on C-5 and terminal alkenes also react in this way to place the alkyl group on C-5. Many dipoles react well with electron-rich dipolarophiles, but not with electron-poor dipolarophiles. Other dipoles are the other way round. To make matters even more complex, the presence of substituents on the dipole can change these patterns and impart their own regioselectivity. Thus the carbonyl ylid reaction 2.45 has a well defined regiochemistry determined only by the substituents, since the core dipole is symmetrical. This reaction also illustrates the point that dipolarophiles do not have to be alkenes or alkynes—they can also have heteroatoms. 

The addition of ZnBi 2 to die tandem 1,3-azaprotio cyclotransfer-cycloaddition of a ketoxime with divinyl ketone results in rate enhancement and the exclusive formation of l-aza-7-oxabicyclo[3.2.1]octan-3-ones.79 The 1,3-dipolar cycloaddition of 1-aza-l-cyclooctene 1-oxide with alkenes produces the corresponding isoxazolidines in high yields with a minimum of polymeric material.80 The cycloaddition of thiophene-2 -carbaldehyde oxime with acetonitrile and methyl acrylate produces the 1,3-dipolar adduct, substituted isoxazolidines, and not the previously reported 4 + 2-adducts.81 Density functional theory and semi-empirical methods have been used to investigate the 3 + 2-cycloaddition of azoxides with alkenes to produce 1,2,3-oxadiazolidines.82 The 3 + 2-cycloaddition of a-nitrosostyrenes (62) with 1,3-diazabuta-l,3-dienes (63) and imines produces functionalized cyclic nitrones (64) regioselectively (Scheme 22).83... 

The parent 2-vinylindole and 2-(2-methylvinyl)indole also reacted with the carbodienophiles methyl-(E)-3-benzoylacrylate, l-penten-3-one, and methyl acrylate these reactions proceeded through a Diels-Alder step to produce the corresponding carbazoles (90JOC5368). The unsymmetrical dienophiles reacted regioselectively in accordance with the predictions of the FMO concept. In none of these reactions was it possible to detect either a betaine intermediate originating from a stepwise process or a Michael-type adduct. The stereochemistry of the cycloadducts was not changed when the reactions were carried out in the polar solvent... 

The use of isoxazole derivatives in organic synthesis is of great interest, but little has been done on the utilization of such compounds as a part of a diene system in [4 + 2]-cycloadditions. 3-Methyl-5-vinylisoxazole 236 gave cycloaddition reactions in a sealed tube in benzene solution at 120°C for 3 days. With the dienophiles acrolein and methyl acrylate, aromatiza-tion of the isoxazole ring via a 1,3-proton shift occurs readily under the reaction conditions, allowing the direct isolation of compounds 237, which are also detected in the mass spectrum of the raw reaction material. The reactions are regioselective (85H2019). 

Predict the regioselectivity in the Diels-Alder reactions of acrolein and N-acetyl-2-cyano-4-phenyl-l-azabutadiene with 1-hexene, styrene, ethyl vinyl ether and methyl acrylate. The FOs of the azadiene are given below the others may be found in the Appendix. 

The preceding sections describe regioselective electrophilic addition of pyrrole complexes at the 3-position with various electrophiles to give ( -substituted lZ/-pyrrole or 3//-pyrrolium isomers. The latter compounds, in contrast to their noncomplexed counterparts, are only moderately acidic (pKa 6) and therefore resist rearomatization and multiple alkylations. For example, when uncomplexed 2,5-dimethylpyrrole is treated with 1 equiv of methyl acrylate and TBSOTf, a statistical 1 2 1 ratio of starting material, monoalkylated 105 (vide infra), and 3,4-bis-alkylated product is found.12 Treatment of 1-methylpyrrole under the same conditions results in at least four alkylated products along with starting material. In contrast, coordination by osmium results in smooth... 

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