Diels-Alder reactions with sigmatropic

Tandem reactions combining Diels-Alder reactions with sigmatropic rearrangements in syntheses of heterocycles 98S227. 

Neuschuetz K., Velker J., Neier R. Tandem Reactions Combining Diels-Alder Reactions With Sigmatropic Rearrangement Processes and Their Use in Synthesis Synthesis 1998 227-255... 

Neuschiitz, K. Velker, J. Neier, R. (1998) Tandem reactions combining Diels-Alder reactions with sigmatropic rearrangement processes and their use in synthesis. Synthesis, 3, 227-55. 

The combination of pericyclic transformations as cycloadditions, sigmatropic rearrangements, electrocydic reactions and ene reactions with each other, and also with non-pericyclic transformations, allows a very rapid increase in the complexity of products. As most of the pericyclic reactions run quite well under neutral or mild Lewis acid acidic conditions, many different set-ups are possible. The majority of the published pericyclic domino reactions deals with two successive cycloadditions, mostly as [4+2]/[4+2] combinations, but there are also [2+2], [2+5], [4+3] (Nazarov), [5+2], and [6+2] cycloadditions. Although there are many examples of the combination of hetero-Diels-Alder reactions with 1,3-dipolar cycloadditions (see Section 4.1), no examples could be found of a domino all-carbon-[4+2]/[3+2] cycloaddition. Co-catalyzed [2+2+2] cycloadditions will be discussed in Chapter 6. 

In contrast to the lack of examples of the domino Diels-Alder reaction/l,3-dipolar cycloaddition, the combination of a Diels-Alder reaction with a sigmatropic rearrangement has been used intensively. 

The fifth chapter l-(2,4,6-Trialkylphenyl)-lH-Phospholes with a Flattened P-Pyramid Synthesis and Reactivity presents the interesting chemistry of these compounds including electrophilic substitution and Diels-Alder reactions and sigmatropic rearrangements, making a variety of organophosphorus compounds accessible. 

The close association between metal ions and p-benzoquinones catalyzes their Diels-Alder reactions with anthracenes. The efficiency of the metal cations correlates with their Lewis acidity171. A mechanism proceeding via radical-anions for a [3,3] sigmatropic rearrangement was established172. 

Cycloadditions The Diels-Alder and the Alder ene reactions [3,3] and [2,3[Sigmatropic rearrangements the aza Cope rearrangement Other pericyclic processes giving nitrogen heterocycles Part II- Cycloadditions to Make Nitrogen Heterocycles Diels-Alder Reactions with Azadienes... 

Knoevenagel products are highly reactive compounds because of their low energy LUMO. They can act as dienophiles in the normal Diels-Alder reaction, as heterodienes in the hetero Diels-Alder reaction with inverse electron demand,- as dipolarophiles in 1,3-dipolar cycloadditions, as enophiles in the ene reaction and as acceptors for the addition of allylsilanes. Sigmatropic rearrangements and photochemical reactions have been described. 

At present it has not been determined unambiguously whether this reaction constitutes an example of direct ,/3-unsaturated thioketone 4ir participation in a [4 + 2] cycloaddition or 2ir thiocarbonyl Diels-Alder reaction with the dienes followed by an undetected [3,3]-sigmatropic rearrangement.7d... 

Of the four possible pathways, it has been empirically determined that vinylnitroso compounds bearing (3 substituents participate as 2ir dienophile components in Diels-Alder reactions with dienes [Eq. (37), path b]6 78 whereas vinylnitroso compounds lacking (3 substitutents participate as 47t diene components in their Diels-Alder reactions with dienes [Eq. (37), path a].6-76 The potential that the observed 47t participation of vinylnitroso compounds in Diels-Alder reactions with dienes [Eq. (37), path c] may arise from a sequence initiated by the all-carbon Diels-Alder reaction [Eq. (37), path d] followed by a [3,3]-sigmatropic rearrangement to the observed oxazine product [Eq. (38)]... 

In the additions of acetylenedicarboxylic esters to the (penta-l,2,4-trienyl)phosphonic esters 484 (R = Me), both head-to-head and head-to-tail products are formed. The initial reaction is then followed by 1,5-sigmatropic rearrangements to give isomers of benzylic phosphonic diesters, 485 (R = Me) and 486 (R = Me). The trienyl phosphonic esters 487 simi-larly give rise to aromatic phosphonic diesters 488 . The ester 484 (R = Et, R = H) is reactive towards A-phenylphthalimide at room temperature, but the product is not the expected 489 but rather 490, which aromatized on chromatography over alumina . The same trienyl phosphonic diesters undergo Diels-Alder reactions with sulphur dioxide and yield sulpholene adducts 491 and... 

An outstanding example of a branching pathway exploited complementary cyclisation reactions to yield alternative molecular scaffolds (Scheme 1.5). A four-component Petasis condensation reaction was used to assemble flexible cyclisation precursors e.g. 14). Alternative cyclisation reactions were then used to yield products with distinct molecular scaffolds Pd-catalysed cyclisation (- 15a) enyne metathesis (- 15b) Ru-catalysed cycloheptatriene formation (- 15c) Au-catalysed cyclisation of the alcohol onto the alkyne (- 15d) base-induced cyclisation (- 15e) Pauson-Khand reaction 15f) and Miesenheimer [ 2,3]-sigmatropic rearrangement (not shown). Four of these cyclisation reactions could be used again to convert the enyne 15e into molecules with four further scaffolds (17a-d). In addition, Diels Alder reactions with 4-methyl-l,2,4-triazoline-3,5-dione converted the dienes 15b, 17a and 17d... 

The use of ketene equivalents in 4- -2-cycloaddition reactions for organic synthesis has been reviewed. " a-Carbonyl ketenes behave as dienes in Diels-Alder reactions with 4-aryl-2-methyl-2,3-dihydro-l,5-benzothiadiazepines to yield regiospecific cycloadducts. The reactions of diphenylketene with cyclic ( -cw)-l,3-dienes such as cyclopentadiene and cyclohexadiene initially yield the Diels-Alder adducts, which are converted into the Staudinger cyclobutanones by [3,3]-sigmatropic rearrangementsl-Benzyl-l,3-diazabuta-l,3-dienes react with ketenes to produce the 4 - - 2-cycloadducts, substituted l-benzyl-4-(benzylidenimino)-4-phenylazetidin-2-ones, which rearrange into the more stable 5,6-dihydro-3//-pyrimidin-4-ones. The formal 4 - - 2-cycloaddition reaction of ketenimines has been used to synthesize benzoimidazo[l,2-Z ]isoquinolines. ... 

Two other important sigmatropic reactions are the Claisen rearrangement of an allyl aryl ether discussed in Section 18.4 and the Cope rearrangement of a 1,5-hexadiene. These two, along with the Diels-Alder reaction, are the most useful pericyclic reactions for organic synthesis many thousands of examples of all three are known. Note that the Claisen rearrangement occurs with both allylic aryl ethers and allylic vinylic ethers. 

The Diels-Alder reaction of cyclopropenes with 1,2,4,5-tetrazines (see Vol.E9c, p 904), a reaction with inverse electron demand, gives isolable 3,4-diazanorcaradienes 1, which are converted into 4H-1,2-diazepines 2 on heating. The transformation involves a symmetry allowed [1,5] sigmatropic shift of one of the bonds of the three-membered ring, a so-called walk rearrangement , followed by valence isomerization.106,107... 

Diels-Alder reactions of vinylpyrazoles 45 and 46 only occur with highly reactive dienophiles under severe conditions (8-10 atm, 120-140 °C, several days). MW irradiation in solvent-free conditions also has a beneficial effect [40b] on the reaction time (Scheme 4.11). The indazole 48, present in large amounts in the cycloaddition of 45 with dimethylacetylenedicarboxylate, is the result of an ene reaction of primary Diels-Alder adduct with a second molecule of dienophile followed by two [l,3]-sigmatropic hydrogen shifts [42]. The MW-assisted cycloaddition of 46 with the poorly reactive dienophile ethylphenyl-propiolate (Scheme 4.11) is significant under the classical thermal reaction conditions (140 °C, 6d) only polymerization or decomposition products were detected. 

Staudinger observed that the cycloaddition of ketenes with 1,3-dienes afforded cyclobutanones from a formal [2+2] cycloaddition [52] prior to the discovery of the Diels-Alder reaction. The 2+2 cycloadditions were classified into the symmetry-allowed 2+2 cycloaddition reactions [6, 7], It was quite momentous when Machiguchi and Yamabe reported that [4+2] cycloadducts are initial products in the reactions of diphenylketene with cyclic dienes such as cyclopentadiene (Scheme 11) [53, 54], The cyclobutanones arise by a [3, 3]-sigmatropic (Claisen) rearrangement of the initial products. 

Since the number of domino processes which start with a Diels-Alder reaction is rather large, we have subdivided this section of the chapter according to the second step, which might be a second Diels-Alder reaction, a 1,3-dipolar cycloaddition, or a sigmatropic rearrangement. However, there are also several examples where the following reaction is not a pericyclic but rather is an aldol reaction these examples will be discussed under the term Mixed Transformations . 

Alcaide, Aknendros and coworkers developed a combination of a 3,3-sigmatropic rearrangement of the methanesulfonate of an a-allenic alcohol to give a 1,3-bu-tadiene which is intercepted by a dienophile present in the molecule to undergo an intramolecular Diels-Alder reaction [83]. Thus, on treatment of 4-236 with CH3S02C1, the methanesulfonate was first formed as intermediate, and at higher temperature this underwent a transposition to give 4-237 (Scheme 4.51). This then led directly to the cycloadduct 4-238 via an exo transition state. 

A particularly instructive example is the thermolysis of (Z)-l,3,8-nonatriene in which an intramolecular Diels-Alder reaction competes with a sigmatropic [1,5] hydrogen shift (Scheme 24). The use of high pressure here enables a reversal of the selectivity. At 150°C and 1 bar the [1,5] hydrogen shift passing through a monocyclic transition state is preferred. At 7.7 kbar the intramolecular Diels-Alder reaction is preferred due to its bicyclic transition state. 

Lignans have been accessed using an intramolecular allenic Diels-Alder reaction (Scheme 19.21). Alkyne 109 was treated with potassium tert-butoxide at 60°C to afford a mixture of 112 and 113 via intermediates 110 and 111 [25]. Cydoadduct 112 could eventually be transferred to isomer 113 at room temperature by way of a second sigmatropic hydrogen shift. 

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