Pericyclic retro-Diels-Alder reaction

In this section are described those domino reactions which start with a retro-pericy-clic reaction. This may be a retro-Diels-Alder reaction, a retro-l,3-dipolar cycloaddition, or a retro-ene reaction, which is then usually followed by a pericyclic reaction as the second step. However, a combination is also possible with another type of transformation as, for example, an aldol reaction. 

Several types of 1,2-oxazines undergo thermal pericyclic reactions in which the N—O bond is cleaved. Thus (506, R = Me, Ph) undergo a thermal retro Diels-Alder reaction on heating to give the corresponding nitrile and o-benzoquinone methide, which can be intercepted by alkenes (Scheme 56) (90JA5341, 94TL7273). 

A major problem in interpreting pericyclic reactions of radical ions is the difficulty of distinguishing between concerted and nonconcerted paths. The same difficulty occurs in the case of thermal reactions, but the problem here is more acute since there is less scope for the application of subtle experimental techniques. Thus cyclohexene (6) undergoes a retro-Diels-Alder reaction to (7) in the mass spectrometer but the products formed do not enable us to distinguish between a two-step process via the intermediate radical ion (8) and a pericyclic process involving the cyclic transition state (9). 

The parallel between retro-Diels-Alder reactions in the mass spectrometer and the corresponding thermal reactions of neutral cyclohexenes does, however, suggest that both proceed by a common mechanism, i.e., a one-step pericyclic process. This conclusion has been strongly supported by Loudon et al in a very detailed comparison of the thermal and mass spec-... 

Heating of 96 gave the desired nitrone cycloaddition product (98) in excellent yield. This reaction involved a rfJtro-1,3-dipolar cycloaddition, followed by the key intramolecular cycloaddition, another nice example of the use of a rfJtro-cycloaddition to generate a reactive intermediate for use in a pericyclic reaction (recall the generation of acylnitroso compounds via a retro-Diels-Alder reaction). 

The intermediates 2 and 4 can then be traced back to simple precursors via retro-Diels-Alder condensations, which are very well known stereospecific pericyclic reactions. 

Pericyclic reactions in the synthesis of heterocycles 87YGK60. Pummerer reaction in the synthesis of heterocycles 89KGS1299. Retro-Diels-Alder strategy in the synthesis of heterocycles 87S207. Solid-phase synthesis of heterocycles 89BSF237. 

Cycloadditions are characterised by two components coming together to form two new a bonds, one at each end of both components, joining them together to form a ring, with a reduction in the length of the conjugated system of orbitals in each component (Fig. 6.1a). Cycloadditions like the Diels-Alder reaction are by far the most abundant, varied, featureful and useful of all pericyclic reactions. They are inherently reversible, and the reverse reaction is called a retro-cycloaddition or a cycloreversion. 

For some time it has been known that many pericyclic reactions can be greatly accelerated if they are run under single electron transfer (SET) conditions (also known as electron transfer catalysis, ETC). Examples include Diels-Alder reactions, electrocyclic openings of cyclobutenes, and retro [2-1-2] cycloadditions. From the beginning it has been debated whether these SET reactions really are concerted processes with aromatic transition states, or whether they are better thought of as stepwise processes involving radical cation intermediates. 

The retro-Diels-Alder step envisages homolytic disconnection of two bonds in the 2,3-position related to the double bond of the cyclohexene ring. Two electrons of each o bond and two electrons from the n bond move to the neighbor o bonds (Scheme 2.5a). Such disconnection corresponds to the pericyclic or concerted character of the Diels-Alder reaction [1, 2]. 

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