Diels-Alder reaction, intramolecular regioselectivity

The first step is an intramolecular Diels-Alder reaction. The regioselectivity of this transformation may be explained as follows The reaction can yield annelated products of type 34 by cyclization in a quasi ortho sense or bridged products of type 36 by cylization in a... 

Scheme 24 Asymmetric intramolecular Diels-Alder reaction and regioselective hydroboration of...

The cycloaddition of photoenol of o-methylbenzaldehyde 66 with 5-alkyli-dene-l,3-dioxane-4,6-dione derivatives 67 is an example of a photo-induced Diels Alder reaction in which one component, the diene in this case, is generated by irradiation [48]. The yields of some cycloadducts 68, generated by photo-irradiation of a benzene solution of 66 and 67 at room temperature, are reported in Table 4.14. The first step of the reaction is the formation of (E)-enol 69 and (Z)-enol 70 (Equation 4.7) by an intramolecular hydrogen abstraction of 66 followed by a stereo- and regioselective cycloaddition with... 

Very recently, Cook and Danishefsky [24] reported an interesting regioselectivity of intramolecular Diels-Alder reactions reversed by the change in the dienophihc moieties from vinyl to allenyl group (Scheme 19). For R = 2-propenyl group, C is bonded to the methyl substituted carbon Cj of the cyclohexadienone ring. For R = 2,3-butadienyl, C is bonded to Cy... 

An intramolecular version of the Diels-Alder reaction with a diene-carboxylate was used by Williams et al. in the synthetic study of the antibiotic ilicicolin H.91 The interesting aspect of this work is that they found that under aqueous conditions, there is an observed reversal of regioselectivity (Eq. 12.31). In toluene, there is a 75 25 ratio of a/b while in degassed water the ratio of a/b is 40 60. 

Methods for the synthesis of substituted pyridines remains an intense topic of research. One of the most popular approaches to substituted pyridines remains cycloaddition reactions. While this strategy is not new and many examples are in the current literature <00TL10251>, the state-of-the-art has been expanded. Weinreb and co-workers have reported the regioselective synthesis of pyridines (3) via intramolecular oximino malonate hetero Diels-Alder reactions (1 - 2) <00OL4007>. Similarly, the intramolecular [4 + 2] cycloaddition of... 

In the [4 + 2] cycloadditions discussed so far, the enol ether double bond of alkoxyallenes is exclusively attacked by the heterodienes, resulting in products bearing the alkoxy group at C-6of the heterocycles. This regioselective behavior is expected for [4+2] cycloadditions with inverse electron demand considering the HOMO coefficients of methoxyallene 145 [100]. In contrast, all known intramolecular Diels-Alder reactions of allenyl ether intermediates occur at the terminal C=C bond [101], most probably because of geometric restrictions. 

Friedrichsen and co-workers (135), along with Padwa, has utilized the carbonyl ylide cycloaddition to generate reactive furan moieties that can be further used in inter- or intramolecular Diels-Alder reactions to prepare aza- and carbocyclic compounds. Friedrichsen conducted a number of synthetic and theoretical studies on the reactivity, regioselectivity, and stereoselectivity of substituted furan formation and subsequent Diels-Alder reaction (Scheme 4.69). 

Theoretically, the regioselectivity observed in photochemical [2 + 2] cycloaddition of 56 with 1,1-dimethoxyethene is in good agreement with experimental results and has been explained on the basis of pertubational molecular orbital theory." Hartke and co-workers" described an interesting contrast in the reactivity of tropolones in an intramolecular Diels-Alder reaction (Scheme 6.18). Thus, alkylation of 64a and 64b with 65 gave 66a and 66b, respectively, that were subjected to cyclization in refluxing toluene. Whereas 66a decomposed under the reaction conditions, 66b afforded 67b in high yield. 

Electrophilic substitution hexahydrophenanthrenes. Electrophilic attack could occur at three sites in 1, but no products of a-substitution have been reported. Benzyl bromide reacts exclusively by y-attack. Aldehydes and ketones react usually by e- and/or y-attack, but with variahlc regioselectivity. c-Attack is useful because products can be obtained that undergo an intramolecular Diels-Alder reaction. An example is the synthesis of the two isomeric hexahydrophenanthrenes (3, equation... 

Molecular electrostatic potentials have been used to explain the regioselectivity exhibited in the Diels-Alder cycloaddition reactions between 1-trimethylsilyloxy-butadiene and the quinones 5-formyl-8-methyl-1,4-naphthoquinone, 5-methoxy-7-methyl-1,4-phenanthrenequinone, and 5,6,7-trimethyl-1,4-phenanthrenequinone.128 The intramolecular Diels-Alder reaction of masked o-benzoquinones (123) with a variety of dienes provides adducts (124) which rearrange to functionalized ris-decal ins (125) with complete stereocontrol of up to five stereocentres. This methodology ... 

While the syntheses of the acyclic precursors in the examples above each require a couple of steps, symmetrical dienynes with a central triple bond and heteroatoms in the tethers are more easily accessible. They can yield heterotricyclic compounds by the same reaction mode, for example, the diaza- and dioxatricycles 121 are obtained starting from dienynes 119 (Scheme 18) [73]. Yields were best (90%) with N-tosyl linkers, with N-Boc groups the reaction was slower (41% yield), and with N-benzyl linkers only decomposition occurred. This may be due to coordination and blocking of the catalyst by the more Lewis-basic amines. The cis- and frans-diastereomers of 121 were formed in a ratio of 1.8 1, and this ratio did not change in other solvents, at different temperatures, with other catalyst precursors or under high pressure (10 kbar). In view of the apparent influence of the tether, the unsymmetrical oxazaprecursor 122 gave a 7 3 mixture of tricycles 123 and 124. Obviously, the hydridopalladation of the triple bond occurred with some regioselectivity such that intramolecular carbopalladation of the allyl-amine predominated. It is noteworthy that in these cases the intramolecular Diels-Alder reactions of the intermediate trienes 120 already occur under the employed conditions, i.e. at 80 °C. 

In a series of papers under the rubric of Intramolecular Diels-Alder Reactions during 1963-1976, the cyclization inter alia of phenylpropargyl phenylpropiolate esters, i.e., functionality designed to produce arylnaphthalene lactones essentially in one step, was extensively examined (105). With the aryl rings differently substituted by the common substituents, there is little regioselectivity in the cyclization step. A... 

Strained cage compounds can be made by intramolecular photocycloaddition of properly designed ene/enone substrates. In an interesting example from J. R. Scheffer, a ben-zoquinone derived Diels-Alder product is regioselectively transformed into a (halO cage compound. This is a more complicated version of the classical intramolecular photochemical cyclization reactions of benzoquinone derivatives (for example see B. Pandey s cage synthesis from a naphthoquinone-cyclopentadiene in Chapter 3). 

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