Diels-Alder reaction steric effects

What the PNS cannot deal with is the effect on reactivity by factors that only operate at the transition state level but are not present in either reactant or product. Examples mentioned in this chapter include transition state aromaticity in Diels Alder reactions, steric effects on reactions of the type A + B ty C + D, or hydrogen bonding/electrostatic effects that stabilize the... 

The substituents at C-2, C-3 within diene 97 and those at C-1, C-2 within dienophiles 98-100 are electronically and/or sterically equivalent with respect to diene and dienophile reaction centers, respectively, and therefore cycloaddition should not display regiochemical bias in the absence of orientational effects. The Diels-Alder reactions of 97 prepared in situ with 98-100 gave an excess of 101 (Scheme 4.19) [70b], which are the expected regioisomers if the reagents react in their preferred orientations within a mixed micelle with an ammonium head group at the aggregate-water interface and the remainder in the micelle interior. 

The reaction is also sensitive to steric effects thus of the three iso-merides of 1,4-diphenylbutadiene (88a — 88c), only the trans-trans form (88a) will undergo a Diels-Alder reaction ... 

Besides the above configurational and steric factors electronic effects of substituents have also been studied on Diels-Alder reaction. How the electronic and steric factors both operate is best afforded by cyclobutadiene which is a highly reactive species and undergoes Diels-Alder reaction even at very low temperature to give a mixture of the following two products. 

In an approach by Jung and Nishimura, the assembly of the dysidiolide decalin skeleton 54 was deemed possible via an intermolecular Diels-Alder reaction between cydohexene 52 and dienophile 53 [14]. Based on precedent established by Wulff et al. [15] [where Z = C(OCH3)=Cr(CO)5], the cycloaddition should give predominantly the exo isomer as shown (Scheme 19.12). However, all attempts to effect the cydoad-dition simply gave recovery of starting material. It was reasoned that steric hindrance was to blame. The steric hindrance assodated with the dienophile was decreased by replacing one of the methyl groups with another double bond in the... 

An increase of char yield is generally reflected as an improvement in oxygen index. In the styrylpyridine based polyesters and polycarbonate an intermolecular thermally induced Diels-Alder reaction has occurred through the double bond, this increased the char yield and decreased the flammability. The Fries rearrangement, as well as dimerization and isomerization, occurred simultaneously during the UV irradiation of p-VPPB, but no dimerization or isomerization occurred for p,p -BVPDPC, probably due to steric effects. 

A modern valence-bond description of the Diels-Alder reaction has been presented. The method of reaction classification by similarity has been expanded to include the effect of steric congestion in the classification of cycloaddition reactions. ... 

A similar enantiomer-selective activation has been observed for aldol " and hetero-Diels-Alder reactions.Asymmetric activation of (R)-9 by (/f)-BINOL is also effective in giving higher enantioselectivity (97% ee) than those by the parent (R)-9 (91% ee) in the aldol reaction of silyl enol ethers (Scheme 8.12a). Asymmetric activation of R)-9 by (/f)-BINOL is the key to provide higher enantioselectivity (84% ee) than those obtained by (R)-9 (5% ee) in the hetero-Diels-Alder reaction with Danishefsky s diene (Scheme 8.12b). Activation with (/ )-6-Br-BINOL gives lower yield (25%) and enantioselectivity (43% ee) than the one using (/f)-BINOL (50%, 84% ee). One can see that not only steric but also electronic factors are important in a chiral activator. 

The asymmetric hetero-Diels-Alder reaction of aldehydes with Danishefsky s diene catalyzed by Ti catalysts generated from a library of 13 chiral ligands or activators has also been reported (Scheme 8.18). The catalyst library contains 104 members. The Ti catalysts bearing L, L , L, and J are found to have a remarkable effect on both enantioselectivity (76.7-95.7% ee) and yield (63-100%). On the other hand, ligands bearing sterically demanding substituents at the 3,3 -positions are found to be detrimental to the reaction. The optimized catalysts, both L /Ti/L and L /Ti/L , are the most efficient for the reaction of a variety of aldehydes, including aromatic, olefinic, and aliphatic derivatives. 

Diels-Alder reactions of oxazoles afford useful syntheses of pyridines (Scheme 53) (74AHC( 17)99). A study of the effect of substituents on the Diels-Alder reactivity of oxazoles has indicated that rates decrease with the following substituents alkoxy > alkyl > acyl >> phenyl. The failure of 2- and 5-phenyl-substituted oxazoles to react with heterodienophiles is probably due to steric crowding. In certain cases, bicyclic adducts of type (359) have been isolated and even studied by an X-ray method (87BCJ432) they can also decompose to yield furans (Scheme 54). With benzyne, generated at 0°C from 1-aminobenzotriazole and lead tetraacetate under dilute conditions, oxazoles form cycloadducts (e.g. 360) in essentially quantitative yield (90JOC929). They can be handled at room temperature and are decomposed at elevated temperatures to isobenzofuran. 

Introduction of a silyl group, such as Me3Si and (t-Bu)Me2Si, on the oxygen of a propar-gylic alcohol181,182 or on vinylallenes183 affects the feasibility and the stereochemical course of intramolecular Diels-Alder reactions with an alkynyl diene, maleic anhydride or TV-methylmaleimide. A possible explanation involves steric effects. 

The stereochemical outcome of the Diels-Alder reaction was rationalized from steric interactions existing in the two possible transition states (Scheme 43). The use of the Lewis acids as catalysts, which became associated with the sulfinyl oxygen thus increasing their effective size, improves the stereoselectivity of the reactions. 

Diels-Alder reactions of 3-chloro and 3-ethyl-2-p-tolylsulfinyl-1,4-benzoqui-nones (124 and 125) take place at the C5-C6 unsubstituted double bond with both cyclic and acyclic dienes [109]. This is not unexpected from the electronic and steric effects of the substituents at C-3, which makes more difficult the approach of the dienes (even the acyclic ones) to C2-C3 than to C5-C6. With cyclopentadi-ene, no 7r-facial selectivity is observed under thermal conditions, and it is moderate in the presence of ZnBr2 (Scheme 63). Slightly higher 7r-facial selectivity was observed in reactions with 2,3-dimethyl-l,3-butadiene, presumably due to the lower reactivity of the diene. 

An even greater steric effect of the Lewis acid catalyst is observed with the organoaluminum reagents 4-6 in the Diels-Alder reactions of an aldehyde with a diene (equation III). 

Whereas in the case of fra j-piperylene a [4+2] cycloadduct is formed with the standard silaethene, no such product is formed in the case of c/j-piperylene but only a [2+2] cycloadduct (Scheme 11) [26]. Obviously, the [4+2] cycloaddition proceeds here more slowly than the unfavored [2+2] cycloaddition. In this sense, silico Diels-Alder reactions are influenced by conformative effects of the organic dienes like Diels-Alder reactions [27] a displacement of the transoid/cisoid equilibrium in the direction of the transoid isomer on steric grounds decreases the rate of cycloadditions. 

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