Solvent effects cycloaddition

Recently the solvent effect on the [4+2] cycloaddition of singlet oxygen to cyclic dienes has been subjected to a multiparameter analysis. A pre-equilibrium with charge-transfer character is involved, which is affected by the solvent through dipolarity-polarisability (n ) and solvophobic interactions ( Sjf and Another multiparameter analysis has been published by Gajewski, demonstrating the... 

Most Diels-Alder reactions, particularly the thermal ones and those involving apolar dienes and dienophiles, are described by a concerted mechanism [17]. The reaction between 1,3-butadiene and ethene is a prototype of concerted synchronous reactions that have been investigated both experimentally and theoretically [18]. A concerted unsymmetrical transition state has been invoked to justify the stereochemistry of AICI3-catalyzed cycloadditions of alkylcyclohexenones with methyl-butadienes [12]. The high syn stereospecificity of the reaction, the low solvent effect on the reaction rate, and the large negative values of both activation entropy and activation volume comprise the chemical evidence usually given in favor of a pericyclic Diels-Alder reaction. 

The hetero-Diels-Alder reaction can also employ dienes containing heteroatoms. Cycloaddition of substituted styrenes with di-(2-pyridyl)-1,2,4,5-tetrazine was investigated by Engberts (Eq. 12.56).127 Again, the rate of the reaction increased dramatically in water-rich media. Through kinetic studies, they showed that the solvent effects on the... 

An unusual solvent effect was observed in cycloadditions of aromatic nitrile N-oxides with alkyl-substituted p-benzoquinones in ethanol-water (60 40) the reaction rates were 14-fold greater than those in chloroform (148). The use of ion pairs to control nitrile oxide cycloadditions was demonstrated. A chiral auxiliary bearing an ionic group and an associated counterion provides enhanced selectivity in the cycloaddition the intramolecular salt effect controls the orientation of the... 

These recent results illustrate for the first time that metallocene-based chiral Lewis acids can serve effectively in providing [4+2] cycloaddition products with excellent levels of enantiofacial selectivity. Perhaps more importantly, the reported NMR studies and the observed dramatic solvent effect should pave the way for future endeavors in the rational design of better chiral metallocenes. 

A third mechanistically distinct [3 -1- 2] cycloaddition between vinyl ethers and vinyl-carbenoids was discovered and reported in 2001 [26]. This reaction is remarkable because when Rh2(S-DOSP)4 is used as the catalyst, the cis-cyclopentenes 142 are formed in up to 99% enantiomeric excess. The reaction occurs between vinylcarbenoids unsubstituted or alkyl-substituted at the vinyl terminus and vinyl ethers substituted with an aryl or vinyl group. Some illustrative examples are shown in Tab. 14.12. The reaction is considered to be a concerted process, which would be consistent with the highly stereoselective nature of the reaction [26]. Contrary to the [3-1-2] cycloaddition derived by means of vinylogous carbenoid reactivity, this latest [3 -1- 2] cycloaddition is not influenced by solvent effects. Due to steric demands on the carbenoid, the [3-1-2] cycloaddi-tion only occurs with cis-vinyl ethers. 

Another focus of this chapter is the alkynol cycloisomerization mediated by Group 6 metal complexes. Experimental and theoretical studies showed that both exo- and endo- cycloisomerization are feasible. The cycloisomerization involves not only alkyne-to-vinylidene tautomerization but alo proton transfer steps. Therefore, the theoretical studies demonstrated that the solvent effect played a crucial role in determining the regioselectivity of cycloisomerization products. [2 + 2] cycloaddition of the metal vinylidene C=C bond in a ruthenium complex with the C=C bond of a vinyl group, together with the implication in metathesis reactions, was discussed. In addition, [2 + 2] cycloaddition of titanocene vinylidene with different unsaturated molecules was also briefly discussed. 

As an alternative, Firestone proposed a stepwise reaction course for the cycloaddition involving biradical intermediates (Scheme 6.13). This reaction course was based on a number of experimental facts such as small solvent effects as well as the formation of byproducts such as oximes (15,109,110). 

The characteristic features of hydroboration of alkenes—namely, regioselec-tivity, stereoselectivity, syn addition, and lack of rearrangement—led to the postulation of a concerted [2 + 2] cycloaddition of borane353,354 via four-center transition state 37. Kinetic studies, solvent effects, and molecular-orbital calculations are consistent with this model. As four-center transition states are unfavorable, however, the initial interaction of borane [or mentioned monobridged dimer, Eq. (6.56)] with the alkene probably involves an initial two-electron, three-center interaction355,356(38, 39). 

A closely related 1,3-dipolar cycloaddition mechanism with an 1,2-dioxolane intermediate227 could not be experimentally proved 228 Further studies concerning details of the mechanism, including molecular-orbital calculations229,230 and solvent effects,231-234 have been carried out, leading, for instance, to the suggestion of the formation of a nonsymmetric transition state230 and an electron donor-... 

Also known are 2 + 2 cycloadditions proceeding by way of a bipolar ion, path (b) of Scheme l.28 These reactions occur in situations such as that depicted in Equation 12.14, where the intermediate zwitterion (10) is strongly stabilized. Tetracyanoethylene adds by this mechanism to /Mnethoxyphenyl-,29 alkoxyl-,30 and cyclopropyl-31 substituted olefins. The additions show large solvent effects.32 Partial loss of stereochemistry occurs as in the biradical cases, but it is much less pronounced. 

An alternative two-step mechanism involving a spin-paired diradical intermediate has also been considered for 1,3-cycloadditions.18,68,69 However, ab initio calculations70-72 on a wide variety of 1,3-dipoles and dipolarophiles are found to coincide essentially with a synchronous 1,3-cycloaddition mechanism.15,17 On the other hand, a two-step mechanism passing through two transition states separated by an intermediate has been derived using the MINDO/3 method, and found to be compatible with substituent and solvent effects as well as stereospecificity observed in 1,3-cycloadditions.73 However, several factors beyond FMO interactions, such as closed shell repulsions, geometrical distortions, polarization, and secondary orbital interactions, all influence mechanisms, rates, and regioselectivities in cycloaddition reactions.74... 

The cycloaddition of diazomethane to benzalanilines does not show any pronounced solvent effect with increasing dielectric constant of the solvent, there is hardly any increase in reaction rate with the exception of protic (e.g., water, alcohols) and dipolar aprotic solvents (e.g., DMF) that produce a significant acceleration in the reaction rate.182 The protic-dipolar aprotic solvent effects are found to be dependent on the electron-withdrawing or... 

The solvent effects on the reaction outcome from 36 with 37 may be rationalized in terms of 1,2-addition to give an initial dipolar intermediate in the polar solvent, MeCN, followed by fused azetine formation and electrocyclic ring opening to afford 38. In the less polar solvent, Et20, 1,4-cycloaddition may proceed without any dipolar intermediate,... 

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