Diels Alder reactions attractive interaction

In summary, it seems that for most Diels-Alder reactions secondary orbital interactions afford a satisfactory rationalisation of the endo-exo selectivity. However, since the endo-exo ratio is determined by small differences in transition state energies, the influence of other interactions, most often steric in origin and different for each particular reaction, is likely to be felt. The compact character of the Diels-Alder activated complex (the activation volume of the retro Diels-Alder reaction is negative) will attenuate these eflfects. The ideas of Sustmann" and Mattay ° provide an attractive alternative explanation, but, at the moment, lack the proper experimental foundation. 

The same conclusions are drawn by analysis of the frontier orbitals involved in cycloadditions. For the most common case of the Diels-Alder reaction, which involves dienophiles with electron-attracting substituents, the frontier orbitals are l/2 of the diene (which is the HOMO) and n of the dienophile (which is the LUMO). Reaction occurs by interaction of the HOMO and LUMO, which can be seen from the illustration below to be allowed. 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

The chiral catalyst 142 achieves selectivities through a double effect of intramolecular hydrogen binding interaction and attractive tt-tt donor-acceptor interactions in the transition state by a hydroxy aromatic group [88]. The exceptional results of some Diels-Alder reactions of cyclopentadiene with substituted acroleins catalyzed by (R)-142 are reported in Table 4.21. High enantio- and exo selectivity were always obtained. The coordination of a proton to the 2-hydroxyphenyl group with an oxygen of the adjacent B-0 bond in the nonhelical transition state should play an important role both in the exo-endo approach and in the si-re face differentiation of dienophile. 

Mataka and coworkers reported the studies of the Diels-Alder reactions of [3.3] orthoanthracenophanes 96 and 97, of which anthraceno unit, the potential diene, has two nonequivalent faces, inside and outside. The reactions of 96 with dien-ophiles gave the mixtures of inside and outside adducts with the ratios between 1 1 and 1 1.5. However, the ratio changes drastically, in favor of the inside adducts, when 97 reacts with dienophiles such as maleic anhydride, maleimide and naphto-quinone [55] (Scheme 46). Mataka suggested that the Jt-facial selectivity is controlled by an orbital interaction between the electron-poor dienophiles and the Jt-orbital of the facing aromatics, which would lead to a stabilization of the transition state, while Nishio suggested that the selectivity is due to the attractive k/k or CH/jt interaction [53]. 

The Diels Alder reaction has been an important testing ground for qualitative theories for many years256,257K In this section we consider the importance of nonbonded attractive interactions on Diels Alder reactivity. Our model reaction system is butadiene and the three isomers of dicyanoethylene ... 

The endo selectivity in many Diels-Alder reactions has been attributed to attractive secondary orbital interactions. In addition to the primary stabilizing HOMO-LUMO interactions, additional stabilizing interactions between the remaining parts of the diene and the dienophile are possible in the endo transition state (Figure 3). This secondary orbital interaction was originally proposed for substituents having jr orbitals, e.g. CN and CHO, but was later extended to substituents with tt(CH2) type of orbitals, as encountered in cyclopropene57. 

The Diels-Alder reaction is the reaction of a diene with a mono-ene to form a cyclohexene derivative, an important reaction for the construction of organic intermediates. One of its attractions is the atom efficiency of 100%, no by-products being formed. The mono-ene, or dienophile which may also be an alkync, has a LUMO of low energy while the diene is usually electron rich with a high lying HOMO. The interaction of these two orbitals starts the reaction between the two molecules (Figure 2.33) [26],... 

A particular example is the Diels-Alder reaction,21,22 which attracted interest after a publication23 reporting large rate enhancement and a change in stereochemistry in water for the reaction between cyclopentadiene and methyl vinyl ketone. Hydrophobic interactions between the reacting molecules and hydrogen bonding of water to the carbonyl moiety were found to play the major role in the observed phenomena.14,24,25... 

Arylation, olefins, 187, 190 Arylketimines, iridium hydrogenation, 83 Arylpropanoic acid, Grignard coupling, 190 Aspartame, 8, 27 Asymmetric catalysis characteristics, 11 chiral metal complexes, 122 covalently bound intermediates, 323 electrochemistry, 342 hydrogen-bonded associates, 328 industrial applications, 8, 357 optically active compounds, 2 phase-transfer reactions, 333 photochemistry, 341 polymerization, 174, 332 purely organic compounds, 323 see also specific complexes Asymmetric induction, 71, 155 Attractive interaction, 196, 216 Autoinduction, 330 Axial chirality, 18 Aza-Diels-Alder reaction, 220 Azetidinone, 44, 80 Aziridination, olefins, 207... 

Diels-Alder reaction of 2-bromoacrolein and cyclopentadiene using 10 mol% of titanium catalyst 74 gave the synthetically versatile (R)-bromoaldehyde adduct 75 in 94% yield, 67 1 exo. endo diastereoselectivity, and 93% ee. The absolute stereochemical outcome of the reaction is consistent with the proposed transition state assembly 76 in which the dienophile coordinates at the axial site of the metal, proximal to the indane moiety through Ji-attractive interactions. In this complex, the 7t-basic indole and the Ji-acidic dienophile can assume a parallel orientation facilitated by the octahedral geometry of the transition metal. The aldehyde would then react through a preferential s-cis conformation (Scheme 17.27).54... 

Dipole-dipole interactions have been used to assess the conformational populations of 2-haloketones (Eliel et al., 1965). With respect to SS, however, there are few applications in which these and related effects are considered. It is interesting that dipole induction and London dispersion effects were used some thirty years ago to account for the high endo over exo preference in the Diels-Alder reaction (Wassermann, 1965). Although effects are small for any pair of atoms, there are many closely packed atoms in a Diels-Alder transition state. At a carbon-carbon distance of 2-0 a between the atoms to be bonded, the energy favoring endo addition is 2-7 for dipole induction and 3-4 kcal/mole for dispersion in the reaction of cyclopentadiene with p-benzoquinone (Wassermann, 1965). These nonbonding attractive energies cooperate with the secondary HMO effects discussed earlier to lead to an endo product. 

Hawkins et al. described a simple and efficient catalyst for the Diels-Alder reaction based on a chiral alkyldichloroborane (Eq. 15) [16]. A molecular complex between methyl crotonate and the chiral catalyst have been isolated for the first time. A study of the crystal structure of the complex enabled the authors to propose a model predicting the approach of the diene on one of the faces of the methyl crotonate, because the other face is protected by n-n donor-acceptor interactions. This secondary attractive substrate-catalyst interaction is the basis of the stereocontrol. 

In a study of enantioselective Diels-Alder reactions catalyzed by CAB 3 derived from A -(arylsulfonyl)-L-a-amino acids, Scheeren et al. [221] varied the position of electron donor functionality in substituent R (Eq. 13), thereby influencing steric repulsion and/or electronic attractive interactions. The experimental results show that enantioselectivity is controlled by the presence of electron donor atoms in positions 2 and 4 (Eq. 21). 

The absolute stereo-preference in the Diels-Alder reaction can be easily understood in terms of the most favorable transition-state assembly 5, in which an attractive donor-acceptor interaction favors coordination of the dienophile at the face of boron which is cis to the 2-hydroxyphenyl substituent. At this time, the conformation of a,y3-enal has a strong s-trans preference. We believe that the coordination of a proton of the 2-hydroxyphenyl group with an oxygen of the adjacent B-O bond in complex 5 plays an important role in asymmetric induction this hydrogen-bonding interaction via a Brpnsted acid would cause the Lewis acidity of boron and the jr-basicity of the phenoxy moiety to increase, and the transition-state assembly 5 would be stabilized. The jr-basic phenoxy moiety and the jr-acidic dienophile could then assume a parallel orientation at the ideal separation (3 A) for donor-acceptor interaction. In this conformation, the hydroxyphenyl group blocks the si face of the dienophile, leaving the re face open to approach by diene. 

Furthermore, y-CD can complex two guests at the same time. For example, two stilbene [135], naphthalene [136], or anthracene [137] moieties can fit in the y-CD cavity. Attractive interactions between the end groups of two included guests enhance the stability of the ICs [136], Because of the close proximity between two included guests, bimolecular reactions like [2+ 2]-cycloadditions [135] and Diels-Alder-reactions [138-140] are strongly accelerated by these ICs. 

The stereochemistry of exo closure in a case like the radical 7.92, giving the cis product 7.94 (cis. trans 72 28), is controlled by the usual preference for the resident substituent to adopt an equatorial orientation 7.93 and for the chain of atoms to adopt a chair-like conformation.1031 In the case of a radical like 7.95, however, there is a clearly contrathermodynamic preference for the formation of the cis product 7.97.1032 It has been suggested that the endo-like transition structure 7.96 might have an attractive secondary orbital interaction from the filled hyperconjugative orbitals with the n orbital, rather like that used to explain the endo rule for Diels-Alder reactions. The preference for cis products like 7.97 does not extend to all substituents on the radical centre, and Z-substituents often lead to trans products, possibly because they lack the same set of orbitals, but probably also because they are larger than a methyl group. 

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