Regioselectivity of Diels-Alder reactions

Table 1.3 Regioselectivity of Diels-Alder reactions of disubstituted 1,3-butadienes with monosubstituted ethenes (RCH=CH2)...

The ability of zeolites to control the regioselectivity of Diels-Alder reaction has been investigated for the cycloaddition of isoprene with various dienophiles [20bj. Some results are reported in Table 4.6. All the zeolites tested afforded high regioselectivity but the reaction yield was generally low and depended on the zeolite as well as on the dienophile. 

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

According to the frontier orbital theory, a bond preferentially forms between the atoms with the largest frontier orbital amplitudes (Sect. 3.4 in the Chapter Elements of a Chemical Orbital Theory by Inagaki in this volume). This is applicable for the regioselectivities of Diels-Alder reactions [15]. The orbital mixing rules are shown here to be useful to understand and design the regioselectivities. 

The regioselectivities of Diels-Alder reactions are also understood in terms of the orbital phase continuity [29]. The selectivity is also explained by the frontier orbital amplitude [30]. 

Fig. 6.2. HOMO-LUMO interactions rationalize regioselectivity of Diels-Alder reactions.

The HSAB Principle at a Local Level Regioselectivity of Diels-Alder Reactions... 

We can customize these general statements specifically for the case of the regioselectivity of Diels-Alder reactions with normal electron demand and make the following statement right away ... 

The consequences for the regioselectivity of Diels-Alder reactions can he summarized as follows. 

Diek-AUer reactions (10, 432-433). The para regioselectivity of Diels-Alder reactions of 1 is improved dramatically by catalytic amounts of aluminum chloride. Examples ... 

The regioselectivity of Diels-Alder reactions ranges from moderate to very high. As shown below in Tables 9.2 and 9.3, the cycloaddition reactions of monosubstituted dienes proceed with good selectivity. Generally, the more powerful the electronic effect of the diene substituent is, the more regioselective is the reaction. 

In conclusion, the special influence of water on the endo/exo selectivity stems from the fact that all effects favouring the endo-adduct are combined in this solvent (1) strong hydrogen bonding, (2) polarity and (3) hydrophobicity. Water also increases the diastereofacial- and the regioselectivity of Diels-Alder reactions. Mechanistic investigations on the reaction between cyclopentadiene and methyl acrylate emphasized the importance of hydrogen-bond donor characteristics and polarity . 

Studies on the kinetics, mechanism and regioselectivity of Diels-Alder reactions with inverse electron demand have been published by Sauer and his group <83TL1481,84TL2541,92BSB52l>. They found that the rate of cycloaddition of cyclooctyne to a number of 1,2,4-triazines can be correlated with the reduction potential of these dienes provided that steric effects are approximately equal. 

The ability to predict the regioselectivity of Diels-Alder reactions is a cornerstone of their use in synthesis. Methyl vinyl ketone, for example, reacted with 2-methyl-1,3-butadiene to give a 3 1 mixture of 69 and 70. Gutsche et al. used the para product (69) to synthesize a-bisabalol. They also reported that using stannic chloride as a catalyst (sec. 11.6.A) increased the ratio of 69/70 to 93 7. ... 

In frontier orbital terms the regioselectivity of Diels-Alder reactions is mainly controlled by the atomic orbital coefficients of the frontier orbitals of both reaction partners. The regioselectivily observed for substituted dienes with a, )-unsaturated carbonyl compounds is shown below. With substituents at C-1 of the diene the 3,4-disubstituted cyclohex-1-enes are preferably obtained. The formation of 1,4-disubstituted cyclohex-1-enes is favored in cycloaddition reactions of C-2-substituted dienes. In cycloaddition reactions of electron-poor alkenes with 1,3-disubstituted dienes generally a preference for the 1,3,4-trisubstituted cyclohex-1-enes is observed. 

Smith NM, Swaminathan Iyer K, Cotry B. The confined space inside carbon nanotubes can dictate the stereo- and regioselectivity of Diels-Alder reactions. Phys Chem Chem Phys... 

A trimethylsilyl group has little effect on the regioselectivity of Diels-Alder reaction. Eor example see Hayama T, Tomoda S, Takeuchi Y, Nomura T (1984) J Org Chem 49 3235 Kloek JA (1981) J Org Chem 46 1951 Hermeling D, Schafer HJ (1984) Angew Chem Int Ed Engl 23 233... 

Regioselectivity of Diels-Alder reaction depends on the position of substituents in both diene and dienophile. Usually four types of D-A reactions are observed (Scheme 3.1)... 

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