Retrocycloaddition reactions

Grigg et a/.472,473 reported the first examples of the elimination of hydrogen cyanide and nitriles in retrocycloaddition reactions. The oxazoles 4 (R = H or Me) with DMAD in cold ether led directly to the furan 6 and the appropriate nitrile the expected intermediate 5 could not be isolated. The less reactive oxazole 7 was converted by DMAD into the furan 8 (69%) and benzonitrile only in boiling toluene about 10%... 

A cycloaddition reaction [18] is the joining together of two independent jt-bonding systems to form a ring with two new a bonds. The reverse is called a retrocycloaddition reaction, and the selection rules apply in both directions of a given reaction. 

The cycloaddition of azides with alkenes is a favorable process, leading to dihydrotriazoles. However, in some cases, these dihydrotriazoles can evolve to the corresponding triazoles, by elimination, fragmentation, or retrocycloaddition reactions. 

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... 

The 5-triflate of 1,3-dioxin undergoes a variety of facile Pd-catalysed cross coupling reactions affording 5-substituted 1,3-dioxins from which acrolein can be thermally generated in high yield by a retrocycloaddition. In particular, this approach leads to a new class of 2-acylacroleins (Scheme 61) <00T10275>. 

Glycine acts as an acid-base catalyst in this reaction. C8 and Cl 1 are very acidic, and once deprotonated they are very nucleophilic, so they can attack C2 and C3 in an aldol reaction. Dehydration gives a key cyclopentadienone intermediate. (The mechanism of these steps is not written out below.) Cyclopentadienones are antiaromatic, so they are very prone to undergo Diels-Alder reactions. Such a reaction occurs here with norbomadiene. A retro-Diels-Alder reaction followed by a [4 + 1] retrocycloaddition affords the product. 

The fragmentation strategy is based on a similar concept to traceless solid-phase chemistry, like retrocycloaddition cleavage, cycloelimination or cyclofragmentation. These are synthetically useful reactions with wide scope for the construction of rigid templates of different ring sizes. Up to now only one example for the attachment of heteroatoms via addition/elimination strategy has been developed, by Kurth et al. (Scheme 3.7) [188, 189]. 

Reactions which formally can be classified as cycloadditions or retrocycloadditions have been observed in homogeneous solution with single electron oxidative initiation, so the observation of parallel activity on irradiated semiconductor suspensions is certainly reasonable. The first example of such a reaction involved the photocatalysis by ZnO or CdS of the ring-opening of a strained hydrocarbon which could also be opened in the dark by a single electron oxidant, ceric ammonium nitrate, Eq. (38)... 

Whether cis or trans fusion is observed in nitrone cycloadditions can depend on reaction conditions as first determined by LeBel et al.9 At lower temperature where cycloaddition is irreversible, kinetic control prevails and this usually favors cis fusion. However, at higher temperature equilibration can occur through retrocycloaddition and the more stable product will predominate (i.e. thermodynamic control). The nitrone may also undergo ( )/(Z) isomerization, particularly at elevated temperature, and this complicates the analysis a different kinetically favored ratio might prevail. A recent example of temperature dependence involves formation of isoxazolidines (18) and (19) from aldehyde (17a Scheme 4). At 90 C ds-fused (18) and rrans-fused (19) were formed in 74% and 9% yield, respectively. At 140 C, however, (18) and (19) were formed in 31% and 34% yield. 

Methylphenylgermylene was generated by retrocycloaddition from the germana-cyclopentane analogue.107 The germylene was detected directly and by analysis of reaction products. Rate constants for the reactions with amines, acids, silanes, stan-nanes, oxygen, and unsaturated carbon-carbon bonds were given. 

Metathesis of alkene 6 to give the new alkenes 11 and 15 is explanined by the following mechanism. The first step is [2+2] cycloaddition between metal carbene 5 and alkene 6 to generate the metallacyclobutane 7 as an intermediate. The real catalyst 8 is generated by retrocycloaddition of the metallacyclobutane 7. Reaction of 8 with alkene 6 generates the metallacyclobutanes 9 and 10 as intermediates. The intermediate 10 is a nonproductive intermediate, which reproduces 6 and 8, while 9 is a productive intermediate and yields the new alkene 11 and the real catalyst 12. Cycloaddition of 12 to alkene 6 produces the productive intermediate 14, from which the new alkene 15 and the active catalytic species 8 are formed. The intermediate 13 is a nonproductive one. 

The thermolysis of phosphatriafulvene 102 gave a set of phosphaalkynes. In this reaction, two phosphetes are considered to be generated by the rearrangement of 102 as an equilibrium mixture of valence isomers. A [2+2] retrocycloaddition then leads to the phosphaalkynes <2001S463>. Contrary to this argument, Dewar-1,3-diphos-phinines are formed upon thermolysis of 102 in the presence of a phosphaalkyne via a 1,3-diphosphinine (Scheme 14). 

This suggests that the formation of quadricyclane during the thermal decomposition of 70 exo results from the competing [2s+2s+2s] retrocycloaddition process rather than via intramolecular trapping of the diradical intermediate by a C-C bond. Thus, the thermal decomposition of 70 exo resulted from [2s+2s+2s] cycloreversion reaction rather than from a biradical pathway. If the latter pathway was active, both exo and endo isomers should have furnished quadricyclane 72. In fact, 70 endo is geometrically incapable to participate in the cycloreversion process. 

Retrocycloaddition Many cycloaddition reactions require moderate heating to overcome the activation energy, but if it is heated too much the equilibrium will favour cycloreversion or retrocycloaddition. For example, cyclopentadiene slowly undergoes cycloaddition with itself one molecule of cyclopentadiene acts as a [4ir]-electrons diene and the other as a [2tt]-electrons dienophile. The product is an endo-tricyclo[5.2.1.0]deca-3,8-diene (8.4), often called dicyclopentadiene. The product 8.4 gives back cyclopentadiene on heating at 150° C for an hour. 

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