Retro-annulations

In the present chapter, however, because the problem is considered from a retrosynthetic point of view, we will distinguish only between heterolytic and homolytic disconnections -to which we will refer to as "retro-annulations"- and concerted or "pericyclic (or cheletropic) cycloreversions". In the same way that Woodward-Hoffmann rules [2] apply to pericyclic reactions, the Baldwin rules [3] may be said to apply to heterolytic as well as to homolytic "monotopic" annulations (see Table 6.1). Although in the preceding Chapter (see 5.5) we have already described some radical "monotopic" annulations, later on in this Chapter (see 6.1.3) and mainly in Chapter 7 we will refer to some new methods, syntheses and strategies which have been developed recently. 

Other general principles applicable to the synthesis of heterocycles refer to cycloreversions (either pericyclic and cheletropic or 1,3-dipolar), valence-bond isomerisations and retro-annulations leading to enamines. 

Strategies based on cycloeliminations (retro-annulations and cycloreversions) which apply mainly to fused polycyclohexane derivatives, such as steroids. 

Some disconnections, as for example, retro-annulations or cycloreversions, greatly simplify the molecular skeleton. 

RINGS, which perform either retro-annulations or cycloreversions which greatly simplify the molecular complexity. 

Under different conditions [PdfOAcj2, K2CO3, flu4NBr, NMP], the 1 3 coupling product 86 with 4-aryl-9,10-dihydrophenanthrene units was obtained. The product 86 was transformed into a variety of polycyclic aromatic compounds such as 87 and 88[83], The polycyclic heteroarene-annulated cyclopen-tadicnc 90 is prepared by the coupling of 3-iodopyridine and dicyclopentadiene (89), followed by retro-Diels Alder reaction on thermolysis[84]. 

A combination of an anionic oxy retro-ene and an aldol reaction to give annulated cyclopentenones 4-361 from 4-358 was described by Jung and coworkers (Scheme 4.80) [126]. It can be assumed that, in the presence of KH, the potassium alkoxide 4-359 is first formed this leads to 4-360 and finally to 4-361 in an intramolecular aldol reaction. 

Annulated pyridines are reported to be synthesized via a [4+2] cycloaddition involving oxazoles (Scheme 121 Table 10) <20010L877>. The reaction mechanism is classified as a domino process with an intramolecular Diels-Alder cycloaddition followed by a retro-Michael reaction. 

Several additional examples of the intramolecular cycloaddition of unactivated acetylenes with isomiinchnones were reported by Maier [30]. This cycloaddition approach represents an efficient method for providing rapid access to annulated furans present in several sesqui- and diterpenes, such as the panicu-lides [51],furanonaphthoquinones [52],furodysin,andfurodysinin [53,54].The decomposition of acyclic acetylenic diazoimides 102 and 103 with Rh2(OAc)4 resulted in cycloaddition and retro-Diels-Alder extrusion of methyl isocyanate to give annulated furans 104 and 105 in good yield. The overall transformation is closely related to the intramolecular Diels-Alder reactions of acetylenic oxa-zoles extensively studied by Jacobi and coworkers [55]. 

The retro-Diels-Alder reaction is a valuable tool for the synthesis of heterocycles <2003COR1423>. The Diels-Alder/ retro-Diels-Alder reaction of oxazoles with acetylenedicarboxylates has been extensively applied for the synthesis of 3,4-disubstituted furans. In a total synthesis of the alkaloid colchicine, such a reaction has been carried out in an intramolecular mode to yield a [ ]-annulated furan, which served as a synthetic key intermediate (Equation 30) <2000T10175>. 

The process of retrosynthetic matching of a target structure into a sub-goal containing the conjugated cyclohexenone fragment (thus amenable to retro-Robinson annulation simplification) involves the utilization of a combination of... 

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