Intramolecular Diels-Alder cyclisation

J. Herscovici, S. Delatre, and K. Antonakis, Enantiospecific naphthopyran synthesis by intramolecular Diels-Alder cyclisation of 4-keto 2,3-unsaturated C-glycosides, Tetrahedron Leu. 32 1183 (1991). 

Feeding studies to Nocardia argentine sis with - C labelled NAC thioesters of di-, tri-, tetra- and pentaketide intermediates demonstrated regiospecific incorporations into nargenicin 37 (Scheme 18) which are consistent with an intramolecular Diels-Alder cyclisation of a linear nonaketide intermediate (Scheme 19) [72,73]. 

Reaction of a 2,6-dimethylphenol (4) with lead tetraacetate in the presence of an excess of acrylic acid leads to ortho-qainol acrylates (5) which then can lead to tricyclic lactones (6) by intramolecular Diels-Alder cyclisation. ... 

The intramolecular Diels-Alder reactions involving boryl-3-propenoic acid derivatives has been addressed to. So, heating the trienylamide (7) at 80°C in toluene for 15 hours led to a 1/3 mixture of the cycloadducts (8) and (8 ) isolated in 72 % yield (figure 6) l7. The trienylamide (9) could not be isolated since the IMDA occured at the temperature of the coupling step, i,e below 0°C in ether for 30 minutes. This very fast cyclisation led to a 85/15 mixture of cycloadducts (10) and (10 ) having respectively a cis and trans junction in the bicyclic structure. The cis bicyclic structure (10) results from an endo approach of the diene and the dienophile. This is in agreement with literature data l8. 

Benzopyran-3-ones, generated by cyclising dehydration of an ort/to-formyl-arylacetic acids take part in intramolecular Diels-Alder additions, as shown below. ... 

Ring aromatic steroids (72) have been constructed by sequential cobalt-catalysed cyclisation of enetriynes (69), and intramolecular Diels-Alder reaction of the resulting o-quinodimethanes (71) derived... 

Examination of framework molecular models shows that, while the anti isomers 9 and 10 can only undergo polymerisation, the syn isomers 7 and 8 can, in principle at least, dimerise and cyclise the synjexo-R isomer 8 might conceivably be capable of cyclisation, i.e. it could undergo an intramolecular Diels-Alder reaction. At... 

The octatetraene 28 was synthesised by a double Lindlar hydrogenation of dialkyne 27, and underwent a spontaneous 8k conrotatory electrocyclisation followed by a 6k disrotatory electrocychsation of the initial cyclisation product 29 (not isolated). This cascade sequence gave rise to endiandric esters D (30) and E (31). Heating to 100 °C in toluene resulted in an intramolecular Diels-Alder cycloaddition of 31, affording endiandric ester A (32). Endiandric esters B, C, F and G were synthesised analogously from a similar dialkyne precursor. 

Strategies based on very particular and specific reactions, such as Diels-Alder addition, either inter- or intramolecular (see also cycloeliminations), cationic cyclisations (important in the "biomimetic synthesis" of steroids), Pauson-... 

Strategies based on two consecutive specific reactions or the so-called "tandem methodologies" very useful for the synthesis of polycyclic compounds. Classical examples of such a strategy are the "Robinson annulation" which involves the "tandem Michael/aldol condensation" [32] and the "tandem cyclobutene electrocyclic opening/Diels-Alder addition" [33] so useful in the synthesis of steroids. To cite a few new methodologies developed more recently we may refer to the stereoselective "tandem Mannich/Michael reaction" for the synthesis of piperidine alkaloids [34], the "tandem cycloaddition/radical cyclisation" [35] which allows a quick assembly of a variety of ring systems in a completely intramolecular manner or the "tandem anionic cyclisation approach" of polycarbocyclic compounds [36]. 

Cycloadditions only proceeding after electron transfer activation via the radical cation of one partner are illustrated by the final examples. According to K. Mizono various bis-enolethers tethered by long chains (polyether or alkyl) can be cyclisized to bicyclic cyclobutanes using electron transfer sensitizer like dicyanonaphthalene or dicyano-anthracene. Note that this type of dimerization starting from enol ethers are not possible under triplet sensitization or by direct irradiation. Only the intramolecular cyclization ci the silane-bridged 2>. s-styrene can be carried out under direct photolysis. E. Steckhan made use of this procedure to perform an intermolecular [4+2] cycloaddition of indole to a chiral 1,3-cyclohexadiene. He has used successfully the sensitizer triphenylpyrylium salt in many examples. Here, the reaction follows a general course which has been developed Bauld and which may be called "hole catalyzed Diels-Alder reaction". 

Oxazoles readily undergo Diels-Alder type cycloaddition across the 2,5-positions, in parallel with the behaviour of furans (18.7). Thiazole and imidazole do not show this mode of reactivity, however they do react with highly electrophilic alkynes via initial electrophilic addition to the nitrogen, then nucleophilic intramolecular cyclising addition (cf the comparable reactivity of quinohnes, 9.13). ... 

The initial reaction is a Diels-Alder addition to give a mixture of the two possible adducts (PI5.3) and (PI5.4). It can be seen that the former is perfectly set up for a very interesting double intramolecular cyclisation when treated with a Bronsted acid (Figure SI5). 

A Diels-Alder reaction features in two approaches to the cannabinoid nucleus. A quinone methide is postulated in the intramolecular HDA cyclisation of (30) to (31) <97CC1867>, whilst an oxazoline-Cu(lI) complex imparts high enantioselectivity to the formation of the Al-THC precursor (32) <97TL3193>. 

Groves and co-workers [a.237] analysed the oil derived from the pyrolysis of natural rubber in a Py-GC at 500 °G. These researchers showed that the major products were the monomer, isoprene, and the dimer dipentene, with other oligomers up to hexamer also being formed in significant concentrations. It was suggested that the isoprene monomer was formed via a depropagating mechanism in the polymer chain, and that dipentene dimer was formed either by intramolecular cyclisation followed by scission, or by monomer recombination via a Diels-Alder reaction. 

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