Steric nitrone additions

Nitroalkanes show a related relationship between kinetic acidity and thermodynamic acidity. Additional alkyl substituents on nitromethane retard the rate of proton removal although the equilibrium is more favorable for the more highly substituted derivatives. The alkyl groups have a strong stabilizing effect on the nitronate ion, but unfavorable steric effects are dominant at the transition state for proton removal. As a result, kinetic and thermodynamic acidity show opposite responses to alkyl substitution. 

The use of Et3B as a radical initiator makes it possible to carry out the addition of other alkyl radicals to nitrone (286) using alkyl iodides. Good yields have been obtained of products (288b-d) when an excess of the appropriate alkyl iodide was used (Scheme 2.110). It has been established that the yield of alkyl by-products (288a) tends to decrease with the increase of the reaction temperature. The stereochemical features of this reaction are explained by the alkyl radical addition taking place predominantly from the less hindered re-face of (286) to avoid steric interaction with the phenyl group (525). 

In several additions of lithiated methoxyallene 42 to sterically hindered nitrones 92, N-hydroxypyrrolidines 93 were obtained in high yield and with excellent diastereoselectivity (Scheme 8.23) [72, 76]. Primary products 93 smoothly cyclize to give bicyclic compounds as shown in Eqs 8.25 and 8.26. 

Observed adducts arise through exo addition of the lactone to the re-re face of the nitrone 141, which avoids an unfavorable C=0/0-ferf-butyl steric clash. 

Russian workers117 reported the same reduced ring by a different route. When the negatively substituted, sterically hindered mesityl-ketenimine (27) adds to the nitrone 28 the C=N in 27, not the C=C, undergoes the addition to give the oxadiazolidine 29. 

Monosubstituted alkenes such as styrene and methyl acrylate, which are capable of secondary orbital interactions with the nitrone (74), give a stereochemical mixture (77a) from endo and exo addition, but the latter predominates. The unactivated, monosubstituted alkenes give exo addition overwhelmingly with this nitrone. The exo preference can largely be attributed to steric interactions between ring hydrogens and the substituent R in the disfavored endo mode of addition (78TL4647). 

The preference of the steric effect was also demonstrated by the 1,4-addition of silyl nitronate (54) to cinnamaldehyde (55) where the sterically bulky substituents CF3 and f-Bu provided higher regio-, stereo- (synlanti), and enantioselectivities (Scheme 5.16, Table 5.6)... 

Cycloadditions are stereospecific cis additions, as has been shown in several cases using geometric isomers as dipolarophiles . In addition to the rigid structure of norbornene, as well-defined approach is preferred, namely the one that gives an exo adduct, as is shown in (a) above for azides, but also occurs with C-phenyl-N-methyl-nitrone and for diphenylnitrilimine -. The alternative approach of the reactants is sterically hindered in the case of norbornene the steric course of reactions of norbornadiene can be different, as was found using phenyl azide as the 1,3-dipole . 

The Chmielewski group has pubHshed extensive studies on the addition of cycHc nitrones to a,P-unsaturated 8- and yl ctones. While five-membered ring nitrones (e.g., 229) react with 8-lactones (e.g., 230) exclusively via an exo-approach because of unfavorable steric interactions, they react with y-lactones (231) through both endo- and exo-transition states, giving rise to mixtures (Scheme 45) (2006TA68). Lactones bearing substituent groups react in such a way that the nitrone approaches the Tt-bond from the face of the alkene opposite the substituent. Cyclic nitrones can adopt conformations that clearly define the location of a substituent on the dipole. For example, reaction 232 with 231 produced only two... 

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