Transition hetero-Diels-Alder reactions

An important contribution for the endo selectivity in the carho-Diels-Alder reaction is the second-order orbital interaction [1], However, no bonds are formed in the product for this interaction. For the BF3-catalyzed reaction of acrolein with butadiene the overlap population between Cl and C6 is only 0.018 in the NC-transi-tion state [6], which is substantially smaller than the interaction between C3 and O (0.031). It is also notable that the C3-0 bond distance, 2.588 A, is significant shorter than the C1-C6 bond length (2.96 A), of which the latter is the one formed experimentally. The NC-transition-state structure can also lead to formation of vinyldihydropyran, i.e. a hetero-Diels-Alder reaction has proceeded. The potential energy surface at the NC-transition-state structure is extremely flat and structure NCA (Fig. 8.6) lies on the surface-separating reactants from product [6]. 

The two transition states in Figs 8.5 and 8.6 correspond in principle to a metal-catalyzed carho-Diels-Alder reaction under normal electron-demand reaction conditions and a hetero-Diels-Alder reaction with inverse electron-demand of an en-one with an alkene. The calculations by Houk et al. [6] indicated that with the basis set used there were no significant difference in the reaction course. 

In a combined experimental and theoretical investigation it was found that the / -alkyl group in the dienophile gave a steric interaction in the transition-state structure which supported the asynchronous transition-state structure for the Lewis acid-catalyzed carbo- and hetero-Diels-Alder reactions. The calculated transition-state energies were of similar magnitude as obtained in other studies of these BF3-catalyzed carbo-Diels-Alder reactions. 

The transition-state structure of the hetero-Diels-Alder reaction is generally found to be unsymmetrical. Houk et al. have for the reaction of formaldehyde with 1,3-butadiene calculated the C-C and C-0 bond lengths to be 2.133 A and 1.998 A, respectively, in the transition state using ab-initio calculations shown in Fig. 8.12 [25 bj. The reaction of formaldimine follows the same trend for the transition-state structure. 

The hetero-Diels-Alder reaction of formaldehyde with 1,3-butadiene has been investigated with the formaldehyde oxygen atom coordinated to BH3 as a model for a Lewis acid [25 bj. Two transition states were located, one with BH3 exo, and one endo, relative to the diene. The former has the lowest energy and the calculated transition-state structure is much less symmetrical than for the uncatalyzed reaction shown in Fig. 8.12. The C-C bond length is calculated to be 0.42 A longer, while the C-0 bond length is 0.23 A shorter, compared to the uncatalyzed reac-... 

Fig. 8.12 Calculated transition-state structure for the hetero-Diels-Alder reaction of formaldehyde with butadiene [25 bj...

The final class of reactions to be considered will be the [4 + 2]-cycloaddition reaction of nitroalkenes with alkenes which in principle can be considered as an inverse electron-demand hetero-Diels-Alder reaction. Domingo et al. have studied the influence of reactant polarity on the reaction course of this type of reactions using DFT calculation in order to understand the regio- and stereoselectivity for the reaction, and the role of Lewis acid catalysis [29]. The reaction of e.g. ni-troethene 15 with an electron-rich alkene 16 can take place in four different ways and the four different transition-state structures are depicted in Fig. 8.16. 

The theoretical investigations of Lewis acid-catalyzed 1,3-dipolar cycloaddition reactions are also very limited and only papers dealing with cycloaddition reactions of nitrones with alkenes have been investigated. The Influence of the Lewis acid catalyst on these reactions are very similar to what has been calculated for the carbo- and hetero-Diels-Alder reactions. The FMOs are perturbed by the coordination of the substrate to the Lewis acid giving a more favorable reaction with a lower transition-state energy. Furthermore, a more asynchronous transition-structure for the cycloaddition step, compared to the uncatalyzed reaction, has also been found for this class of reactions. 

Tietze, L. F., Pfeiffer, T., Schuffenhauer, A., 1998, Stereoselective Intramolecular Hetero Diels-Alder Reactions of Cyclic Benzylidenesulfoxides and DFT Calculations on the Transition Structures , Eur. J. Org. Chem., 2733. 

Mg11 is often employed in stereoselective reactions. In hetero Diels-Alder reactions of aldehydes with Danishefsky s diene, Mg11 results in good acceleration and stereoselection, and 2,3-coproducts are obtained exclusively (Scheme 6).26 Milder Lewis acidity is necessary for obtaining higher yield and higher stereoselectivity in this reaction, which occurs through a cyclic transition state. 

Such a conclusion is, nevertheless, connected with the synchronous character of the mechanism. If a stepwise process is involved (nonsimultaneous formation of the two new bonds), as for unsymmetric dienes and/or dienophiles or in hetero Diels-Alder reactions, a specific microwave effect could intervene, because charges are developed in the transition state. This could certainly be so for several cycloadditions [47, 48] and particularly for 1,3-dipolar cycloadditions [49]. Such an assumption has... 

An extensive review of the hetero-Diels-Alder reactions of 1-oxabuta-1,3-dienes has been published. Ab initio calculations of the Diels-Alder reactions of prop-2-enethial with a number of dienophiles show that the transition states of all the reactions are similar and synchronous.Thio- and seleno-carbonyl compounds behave as superdienophiles in Diels-Alder reactions with cyclic and aryl-, methyl-, or methoxy-substituted open-chain buta-1,3-dienes.The intramolecular hetero-Diels-Alder reactions of 4-benzylidine-3-oxo[l,3]oxathiolan-5-ones (100) produce cycloadducts (101) and (102) in high yield and excellent endo/exo-selectivity (Scheme 39). A density functional theoretical study of the hetero-Diels-Alder reaction between butadiene and acrolein indicates that the endo s-cis is the most stable transition structure in both catalysed and uncatalysed reactions.The formation and use of amino acid-derived chiral acylnitroso hetero-Diels-Alder reactions in organic synthesis has been reviewed. The 4 + 2-cycloadditions of A-acylthioformamides as dienophiles have been reviewed. ... 

Extensive reviews of Diels-Alder reactions and hetero-Diels-Alder reactions in aqueous media have been presented. " " " " Micelles in the presence of catalytically active transition-metal ions catalyse the Diels-Alder reaction between 3-(/ -substituted phenyl)-l-(2-pyridyl)prop-2-en-l-ones with cyclopentadiene by a factor of 1.8 x 10 compared with the uncatalysed reaction in MeCN. " Diels-Alder reactions have been shown to be accelerated by encapsulation of both reactants by pseudospherical capsules assembled from self-complementary molecules (103). " ... 

Recently, the first examples of catalytic enantioselective preparations of chiral a-substituted allylic boronates have appeared. Cyclic dihydropyranylboronate 76 (Fig. 6) is prepared in very high enantiomeric purity by an inverse electron-demand hetero-Diels-Alder reaction between 3-boronoacrolein pinacolate (87) and ethyl vinyl ether catalyzed by chiral Cr(lll) complex 88 (Eq. 64). The resulting boronate 76 adds stereoselectively to aldehydes to give 2-hydroxyalkyl dihydropyran products 90 in a one-pot process.The diastereoselectiv-ity of the addition is explained by invoking transition structure 89. Key to this process is the fact that the possible self-allylboration between 76 and 87 does not take place at room temperature. Several applications of this three-component reaction to the synthesis of complex natural products have been described (see section on Applications to the Synthesis of Natural Products ). 

Because a comprehensive discussion of the transition state of hydrogen-bond catalysis will be presented by Berkessel in Chapter 3, the hydrogen bond catalyzed hetero Diels-Alder reaction of butadiene with carbonyl compounds will be discussed briefly here. Huang and Rawal reported that the hetero Diels-Alder reaction of aminodiene with aldehyde exhibited significant solvent effects (Scheme 2.7) [15]. The reaction in CHCfi was accelerated 30 times in comparison with that in THF, while that in i-PrOH was accelerated 630 times. They proposed that the Diels-Alder reaction was promoted by the hydrogen-bond activation of aldehyde. This finding resulted in the development of TADDOL catalyst [3]. 

Domingo and Andres reported a DFT study of the hetero Diels-Alder reaction of aminodiene with acetone in CHCfi (Scheme 2.8) [16]. The transition state structure clearly shows that OH distance is 1.837 A (Figure 2.5), which is in the range... 

Figure 2.5 Transition state of the hetero Diels-Alder reaction.

Theoretical work on the gas-phase hetero-Diels-Alder reaction of A -sulfinyl dienophiles was used to study both endo- and o-modes of cycloaddition for both (E)-29 and (Z)-30 dienophiles at the B3LYP/6-31G level (Scheme 2) <2000JOC3997>. In summary, these calculations have predicted that (1) the A -sulfinyl dienophiles prefer the (Z)-30 orientation over (E)-29 stereochemistry by 5-7 kcalmoP, (2) the transition state is concerted but nonsynchronous, and (3) an lYo-transition state with diene 31 is favored over the fvo-approach both kinetically and thermodynamically. 

Pandit and co-workers adopted the same strategy to catalyze a hetero-Diels-Alder reaction in which an aryl-nitroso derivative serves as the dienophile.117 118 Antibodies generated against thebicyclic transition-state analogs 133 and 134 accelerated the reaction between the trans-diene 135 and 136, but the ratio of the two product regioisomers 137 and 138 was the same as for the uncatalyzed reaction (58 42). In experiments with stoichiometric amounts of trans-135 and antibody 309-1G7, derived from hapten 134, this ratio was altered somewhat in favor of product 138 (47 53), in accord with the structure of the... 

Transition-metal complexes with salen ligands can serve as catalysts for a multitude of stereogenic reactions including Diels-Alder reactions. We recently studied the application of polyglycerol-supported salen systems 18, 19 and 20 as chiral catalysts in the hetero Diels-Alder reaction between... 

Scheme 1-2. Transition structures for the intermolecular hetero Diels-Alder reaction of 1 -oxa-1,3-butadienes...

In contrast to the great number of calculations concerning the all-carbon Diels-Alder reaction [39], there are only a few theoretical studies on the hetero Diels-Alder reaction [41,42,45 - 53 ]. The general mechanism of the Diels-Alder reaction is still in discussion however, in most cases a concerted reaction is assumed,but there is also evidence for a two-step path. The ab initio calculations carried out for the butadiene/ethene system by Houk, Ortega, Bernardi und Gajewski gave a symmetrical transition structure only using the semiempirical AM1/CI method (half electron approximation) an unsymmetrical diradicaloid intermediate was found [40]. 

For hetero Diels-Alder reactions it has been shown by calculations that the transition structures are usually less symmetric than for the all-carbon Diels-Alder reactions also a change from a concerted non-synchronous to a stepwise mechanism depending on the substituents at the reacting species and the reaction conditions can occur. 

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