Reverse cycloaddition

Some efforts have also been done to induce chirality in the intramolecular [2 + 2] photocycloaddition of benzene derivatives using a chiral auxiliary [88]. 141b was isolated with a diastereoselectivity of 17% from the intramolecular photocycloaddition of the salicylic acid derivative 140b (Scheme 35) [89]. After an initial [2 + 2] cycloaddition, reversible thermal and photochemical rearrangements took place. These equilibria can be displaced by an acid catalyzed and irreversible addition of methanol to the intermediate P. 

Unexpected exchange behavior was additionally observed in the P-hydrogen region of the NOESY-2D and ROESY-2D spectra of these metallacycles. For example, when 22c was reacted with 1-butene (30equiv) at —80°C, exchange cross-peaks were clearly visible between the P-protons of the trans and cis ruthenacycles. These results indicate that, not only is olefin rotation possible between degenerate cycloadditions/reversions at —80 C, but stereoisomerization is as well. A hypothetical mechanism for this trans-cis exchange (H tians H ds) is shown in Scheme 8.8, where stereochemical interconversion is depicted to... 

As a consequence of the rigid face-to-face orientation, there are strong electronic interactions between the benzene rings in the dibenzo-anellated isodrin derivative. Irradiation with 254-nm UV light gave rise to a 7 3 equilibrium mixture of the educt with the [6 -I- 6]cycloaddition isomer. At an irradiation wavelength of 300 nm the cycloaddition wa completely reversed. 

On the other hand, unsaturated diazo compounds are thermally transformed by 1,1-cycloaddition into a bicyclic pyrazqle (141). Although reversibility of this cycloaddition is... 

A large fraction of the chemical reactions known are used to form heterocyclic compounds. Displacement reactions and cycloadditions are particularly important, and their rates are therefore of great practical interest. The same is true for the rates of reverse reactions — ring opening by displacements or retrocycloadditions. It was realized over the last 40 years that... 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

When both the 1,3-dipoIe and the dipolarophile are unsymmetrical, there are two possible orientations for addition. Both steric and electronic factors play a role in determining the regioselectivity of the addition. The most generally satisfactory interpretation of the regiochemistry of dipolar cycloadditions is based on frontier orbital concepts. As with the Diels-Alder reaction, the most favorable orientation is that which involves complementary interaction between the frontier orbitals of the 1,3-dipole and the dipolarophile. Although most dipolar cycloadditions are of the type in which the LUMO of the dipolarophile interacts with the HOMO of the 1,3-dipole, there are a significant number of systems in which the relationship is reversed. There are also some in which the two possible HOMO-LUMO interactions are of comparable magnitude. 

Only a few reactions of benzodithiadiazines have been investigated. In common with dithiatriazines 12.8, the anti-aromatic system 12.12 (R = H) undergoes a reversible 5,5 -cycloaddition with norbornadiene. The reaction of 12.12 (R = F) with triphenylphosphine results in a ring contraction to give the imino 2 -phosphane 12.13. ... 

Dienamines undergo 1,4 cycloaddition with sulfenes as well as 1,2 cycloaddition. For example, l-(N,N-diethylamino)butadiene (111), when treated with sulfene (generated from methanesulfonyl chloride and triethyl-amine), produces 1,4 cycloadduct 116 in an 18 % yield and di-1,2-cycloadduct 117 in a 60 % yield (160). Cycloadduct 116 was shown not to be the precursor for 117 by treating 116 with excess sulfene and recovering the starting material unchanged (160). This reaction probably takes place by way of zwitterion 115, which can close in either a 1,4 or 3,4 manner to form cycloadducts 116 and 118, respectively. The 3,4 cycloaddition would then be followed by a 1,2 cycloaddition of a second mole of sulfene to form 117. Cycloadduct 117 must form in the 3,4 cycloaddition followed by a 1,2-cycloaddition sequence rather than the reverse sequence since sulfenes undergo cycloaddition only in the presence of an electron-rich olefinic center (159). Such a center is present as an enamine in 118, but it is not present in 119. 

One interesting phenomenon was the effect of the boron substituent on enantioselectivity. The stereochemistry of the reaction of a-substituted a,/ -unsatu-rated aldehydes was completely independent of the steric features of the boron substituents, probably because of a preference for the s-trans conformation in the transition state in all cases. On the other hand, the stereochemistry of the reaction of cyclopentadiene with a-unsubstituted a,/ -unsaturated aldehydes was dramatically reversed on altering the structure of the boron substituents, because the stable conformation changed from s-cis to s-trans, resulting in production of the opposite enantiomer. It should be noted that selective cycloadditions of a-unsubsti-tuted a,/ -unsaturated aldehydes are rarer than those of a-substituted a,/ -unsatu-... 

Substituted TMM complexes also cycloadd to aldehydes in the presence of a tin cocatalyst such as MesSnOAc and MesSnOTs [31]. Reaction of 2-heptenal with methyl precursor (6) gave a mixture of methylenetetrahydrofurans (68) and (69). This regioselectivity is reversed with 10-undecenal and methyl precursor (5), where adduct (70) now predominates over (71). As in the carbocyclic system, the phenylthio group also functions as a regiocontrol element in reaction with cyclohexyl aldehyde. The initially formed adduct (72) eliminates the element of thio-phenol on attempted allyl rearrangement, and the overall process becomes a cycloaddition approach to furans (Scheme 2.21) [20]. 

A rather unexpected discovery was made in connection to these investigations [49]. When the 1,3-dipolar cycloaddition reaction of la with 19b mediated by catalyst 20 (X=I) was performed in the absence of MS 4 A a remarkable reversal of enantioselectivity was observed as the opposite enantiomer of ench-21 was obtained (Table 6.1, entries 1 and 2). This had not been observed for enantioselective catalytic reactions before and the role of molecular sieves cannot simply be ascribed to the removal of water by the MS, since the application of MS 4 A that were presaturated with water, also induced the reversal of enantioselectivity (Table 6.1, entries 3 and 4). Recently, Desimoni et al. also found that in addition to the presence of MS in the MgX2-Ph-BOX-catalyzed 1,3-dipolar addition shown in Scheme 6.17, the counter-ion for the magnesium catalyst also strongly affect the absolute stereoselectivity of the reac-... 

Thermal and photochemical cycloaddition reactions always take place with opposite stereochemistry. As with electrocyclic reactions, we can categorize cycloadditions according to the total number of electron pairs (double bonds) involved in the rearrangement. Thus, a thermal Diels-Alder [4 + 2] reaction between a diene and a dienophile involves an odd number (three) of electron pairs and takes place by a suprafacial pathway. A thermal [2 + 2] reaction between two alkenes involves an even number (two) of electron pairs and must take place by an antarafacial pathway. For photochemical cyclizations, these selectivities are reversed. The general rules are given in Table 30.2. 

The following reaction takes place in two steps, one of which is a cycloaddition and the other of which is a reverse cycloaddition. Identify the two peri-cyclic reactions, and show how they occur. 

Since sulfoxides and sulfones are versatile synthetic intermediates, and since in both the thiolene oxide and dioxides the reverse dethionylation114 ( — SO), and cheletropic extrusion of sulfur dioxide296, respectively, readily take place thermally, these cycloadditions are expected to find a useful place in organic synthesis. It should be kept in mind, however, that the retrograde SO-diene reaction and interconversion of the thiolene oxides compete effectively against SO extrusion on heating, and that diene isomerization accompanies the forward reaction (SO + diene). 

Diene 265, substituted by a bulky silyl ether to prevent cycloaddition before the metathesis process, produced in the presence of catalyst C the undesired furanophane 266 with a (Z) double bond as the sole reaction product in high yield. The same compound was obtained with Schrock s molybdenum catalyst B, while first-generation catalyst A led even under very high dilution only to an isomeric mixture of dimerized products. The (Z)-configured furanophane 266 after desilylation did not, in accordance with earlier observations, produce any TADA product. On the other hand, dienone 267 furnished the desired macrocycle (E)-268, though as minor component in a 2 1 isomeric mixture with (Z)-268. Alcohol 269 derived from E-268 then underwent the projected TADA reaction selectively to produce cycloadduct 270 (70% conversion) in a reversible process after 3 days. The final Lewis acid-mediated conversion to 272 however did not occur, delivering anhydrochatancin 271 instead. 

The Diels Alder reaction is reversible and the direction of cycloaddition is favored because two n bonds are replaced by two cr-bonds. The cycloreversion occurs when the diene and/or dienophile are particularly stable molecules (i.e. 

Cycloalkenones and/or their derivatives can also behave as dienic partners in the Diels-Alder cycloaddition. It is well documented [41] that cyclic acetals, for example, can interconvert with ring-opened enol ether forms, in a reversible manner the latter compounds can then be trapped by various dienophiles. Thus dienes 119 and 120 reacted with [60]-fullerene (Ceo) at high pressure, affording highly thermally stable products [42] (Scheme 5.16). Ketones 123 and 124 could be directly obtained by cycloaddition of enol forms 121 and 122 of 2-cyclopen-ten-and 2-cyclohexen-l-one, respectively. 

The rule may then be stated A thermal pericyclic reaction involving a Hiickel system is allowed only if the total number of electrons is 4n + 2. A thermal pericyclic reaction involving a Mobius system is allowed only if the total number of electrons is 4n. For photochemical reactions these rules are reversed. Since both the 2 + 4 and 2 + 2 cycloadditions are Hiickel systems, the Mdbius-Hiickel method predicts that the 2 + 4 reaction, with 6 electrons, is thermally allowed, but the 2 + 2 reaction is not. One the other hand, the 2 + 2 reaction is allowed photochemically, while the 2 + 4 reaction is forbidden. 

Thus, the frontier-orbital and Hiickel-Mobius methods (and the correlation-diagram method as well) lead to the same conclusions thermal 2 + 4 cycloadditions and photochemical 2 + 2 cycloadditions (and the reverse ring openings) are allowed, while photochemical 2 + 4 and thermal 2 + 2 ring closings (and openings) are forbidden. 

This type of orientation of the newly formed bonds is called antarafacial, and the reaction would be a [ 2s + 4a] cycloaddition (a stands for antarafacial). We can easily show by the frontier-orbital method that this reaction (and consequently the reverse ring-opening reactions) are thermally forbidden and photochemically allowed. Thus in order for a reaction to proceed,... 

Thermal cleavage of cyclobutanesto give two alkene molecules (cyclorever-sion, the reverse of 2 -I- 2 cycloaddition) operates by the diradical mechanism, and the [ 2s -I- o2a] pathway has not been found " (the subscripts a indicate that cr bonds are involved in this reaction). 

It has been found that certain 2 + 2 cycloadditions that do not occur thermally can be made to take place without photochemical initiation by the use of certain catalysts, usually transition metal compounds. Among the catalysts used are Lewis acids and phosphine-nickel complexes.Certain of the reverse cyclobutane ring openings can also be catalytically induced (18-38). The role of the catalyst is not certain and may be different in each case. One possibility is that the presence of the catalyst causes a forbidden reaction to become allowed, through coordination of the catalyst to the n or s bonds of the substrate. In such a case, the... 

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