Retro- cycloaddition

An extensive series of low-temperature matrix isolation experiments has failed to provide any evidence of oxirene formation, either by diazo ketone photolysis (82CB2192) or by attempted photo-retro-cycloaddition (82CB2202). 

N,N -linked synthesis, 5, 269 6,6 -Biazulenes synthesis, 1, All Bibenzimidazolyls 3-oxides synthesis, 5, 412 1,1 - Bibenzimidazolyls synthesis, 5, 459 2,2 -Bibenzo[b]selenienyl synthesis, 4, 947 2,2 -Bibenzothiazolyl reduction, 6, 260 4,4 -Bichromenyl synthesis, 3, 743 Bicyclo[n. 1.0]alkanes retro-cycloaddition reactions, 1, 668 Bicyclo[5.3.0]decane synthesis, 1, 420 Bicyclo[4.1,0]diheteroheptanes synthesis, 3, 977... 

Houk K. N., Wilsey S. L., Beno B. R., Kless A., Nendel M., Tian J. Retro-Cycloadditions and Sigmatropic Shifts The C7H8 and C7H10 Potential Energy Surfaces Pure Appl. Chem. 1998 70 1947-1952... 

Amino-substituted phosphirane complexes undergo retro-cycloaddition at 70-90 °C to give the trappable (OC)5WPNEt2 phosphinidene complex [55]. Other substituted phosphiranes are not suited to generate phosphinidenes because they require elevated temperatures, which typically induce thermal degradation instead. 

Intramolecular cycloadditions are among the most efficient methods for the synthesis of fused bicyclic ring systems [30]. From this perspective, the hetisine skeleton encompasses two key retro-cycloaddition key elements. (1) a bridging pyrrolidine ring accessible via a [3+2] azomethine dipolar cycloaddition and (2) a [2.2.2] bicyclo-octane accessible via a [4+2] Diels-Alder carbocyclic cycloaddition (Chart 1.4). While intramolecular [4+2] Diels—Alder cycloadditions to form [2.2.2] bicycle-octane systems have extensive precedence [3+2], azomethine dipolar cycloadditions to form highly fused aza systems are rare [31-33]. The staging of these two operations in sequence is critical to a unified synthetic plan. As the proposed [3+2] dipolar cycloaddition is expected to be the more challenging of the two transformations, it should be conducted in an early phase in the forward synthetic direction. As a result, a retrosynthetic analysis would entail initial consideration of the [4+2] cycloaddition to arrive at the optimal retrosynthetic C-C bond disconnections for this transformation. 

The tricyclic compound (441) is a key compound in the synthesis of enan-tiomerically pure indolizidine (442). It was obtained in an intramolecular 1,3-cycloaddition of nitrone (440), by retro-cycloaddition from isoxazolidine (439) (Scheme 2.215) (708). 

This is because of retro-cycloaddition. In retro-cycloadditions, the reverse reactions are more favoured and the same selection rules apply. This is also because that X is normally a small inorganic molecule and of high thermodynamic stability. 

The reverse reaction of a cycloaddition is of importance for the construction of catalytic cycles. The retro-cycloadditions of reactions a and b in Figure 2.22 are not productive, unless the structures were obtained via another route. 

Thiophene 1,1-dioxides, unlike most other thiophene derivatives, are dienes and combine with dieneophiles to form adducts that are prone to retro-cycloaddition, extruding sulfur dioxide in the process (Scheme 6.34b). 

Thietane 1,1-dioxide derivatives reportedly produce sulfur dioxide as well as a variety of other fragments. Peaks resulting from retro cycloaddition fragmentation such as CH2S and CH2S02 are never lacking. 

The two-bond disconnection (retro-cycloaddition) approach also often works very well if the target molecule contains three-, four-, or five-membered rings (see section 1.13 and 2.5). The following tricyclic aziridine can be transformed by one step into a monocyclic amine (W, Nagata, 1968). In synthesis one would have to convert the amine into a nitrene, which-would add spontaneously to a C—C double bond in the vicinity. 

Diels-Alder reactions like the one illustrated opposite are cycloadditions mobilising six electrons. The dimerization of cyclopentadiene 1.1 is another Diels-Alder reaction, but also illustrates its inherent reversibility—cracking the dimer 1.2 on heating is called a retro-cycloaddition or a cycloreversion. 

The following reactions take place with combinations of electrocyclic reactions, cycloadditions and retro-cycloadditions, in any order. Identify the steps, and show that all the steps [two in (a), three in (b), and five in (c)] obey the Woodward-Hoffmann rules ... 

Retro-cycloaddition extrusion of the metaphosphate moiety from 2,3-oxa-phosphabicyclo[2.2.2]octene derivatives (79), in 1,2-dichloroethane at 100 °C in the presence of PrOH, has been shown to proceed via an unsymmetrical transition state in which C—P bond breakage and P=0 bond formation are more advanced than C—O breakage.39 The secondary deuterium isotope effect on H adjacent to the P—C bond is 1.060 0.008 for (79a) and 1.081 0.009 for (79b) and the oxygen kinetic isotope effect on the P—O—C bridge is 0.9901 0.0016 for (79a). 

An improved retro-cycloaddition of pyrrolidinofullerenes has been carried out in presence of metal Lewis acids.15 The experimental data suggested that thermal treatment leads to the formation of the azomethine ylide, which is efficiently trapped by the dipolarophile that is present in the reaction medium. 

The continuing accumulation of experimental material made it, however, still more apparent that the above criteria, both kinetic and stereochemical [61-64], cannot be regarded as absolute [65], since there are probably both concerted reactions which are forbidden as well as nonconcerted ones which are allowed. An example of the first type of reaction is some 2 + 2 retro-cycloadditions on sterically strained systems [62,66] the second type of processes is then represented by the so-called multibond reactions [67]. This, of course, stimulates to formulate a new and more universal criterion of concertedness as well as a deeper understanding of the very concept of concertedness. 

In these strategies a double or triple bond results from l,w-elimination processes. These are synthetically useful operations with a wide range of possibilities for construction of rigid templates of different ring sizes. Occasionally, a retro cycloaddition must also be regarded as a fragmentation deavage. 

Addition of N-phenylmaleimide to compound (78 R1 = R2 = Ph) gives a mixture of the exo and endo adducts (80 R1 = R2 = Ph). When pure samples of these are heated in boiling xylene, thermal interconversion of the adducts is observed indicating that under these conditions retro-cycloaddition occurs (69JA6891,79CL1029). The unsubstituted derivative (78 R1 = R2 = H) and N-phenylmaleimide yielded only the endo adduct (80 R1 = R2 = H) (79TL4493). 

A study on fulleroisoxazolines showed that these adducts undergo retro-cycloaddition by heating in the presence of copper(II) triflate as a catalyst and an excess of a dipolarophile to trap nitrile oxide. The electronic nature of the isoxazoline substituents strongly influences the reaction outcome <07JOC3840>. The fulleroisoxazolines 50 functionalized with electron-donor groups have been synthesized and their photophysical properties analyzed <07EJO2175>. 

The Stereoselectivity of Diels-Alder Reactions. One of the most challenging stereochemical findings is Alder s endo rule for Diels-Alder reactions. The favoured transition structure 6.180 has the electron-withdrawing substituents in the more hindered environment, under the diene unit, giving the kinetically more favourable but thermodynamically less favourable adduct 6.181. Heating eventually equilibrates the adducts in favour of the exo adduct 6.182, by a retro-cycloaddition re-addition pathway. 

Lukoyanova, O., Cardona, C.M., Altable, M. eta/. (2006) Selective electrochemical retro-cycloaddition reaction of pyrrolidinofullerenes. Angewandte Chemie International Edition, 45, 7430-7433. 

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