Reversible Diels-Alder cyclization,

Within the diastereomeric switch sequences, the corresponding trans-diols become accessible either using a Mitsunobu inversion or a reversible Diels-Alder cyclization as key reaction step [249,250]. This synthetic strategy is complementary to an approach involving metabolic engineering of E. coli via the chorismate/ isochorismate pathway [251]. 

An ingenious new approach to the synthesis of pseudotabersonine (707) has been developed by Carroll and Grieco (391). Here the intermediate oxindole 708 was constructed by a remarkable process in which the anion from the precursor oxindole 709 was alkylated by Grieco s spiroaziridinium triflate 710. A-Benzylation of the product 711, followed by a reverse Diels-Alder fragmentation, then an intramolecular aza-Diels-Alder cyclization, gave the tetracyclic oxindole 708. Introduction of the three-carbon unit into position 2 in 70iB was achieved by condensation with 2-lithio-l,l-diethoxy-2-... 

Furan (282) can be alkylated a to the SO2 group, but a mixture of mono- and bis-alkylation products is always obtained. Alkene (290b) did not cyclize on heating and the sulfolene-derived diene moiety was unreactive towards intramolecular Diels-Alder cyclization, even following reaction of the furan moiety with dienophiles. However, dienophiles (291a/b) were more reactive and cyclized via (292a/b), which were formed in situ by reversible reaction of the furan with methylvinyl ketone [3] (Scheme 6.83). 

Thermal and photochemical cycloaddition reactions always take place with opposite stereochemistry. As with electrocyclic reactions, we can categorize cycloadditions according to the total number of electron pairs (double bonds) involved in the rearrangement. Thus, a thermal Diels-Alder [4 + 2] reaction between a diene and a dienophile involves an odd number (three) of electron pairs and takes place by a suprafacial pathway. A thermal [2 + 2] reaction between two alkenes involves an even number (two) of electron pairs and must take place by an antarafacial pathway. For photochemical cyclizations, these selectivities are reversed. The general rules are given in Table 30.2. 

One problem associated with An + 2n cyclizations of carbon nanotubes is the reversibility of the process, and for this reason Diels-Alder reactions have been a less used synthetic route. One of the most representative examples of Diels Alder functionalization was reported by Langa and co-workers, who performed MW-assisted addition of o-quinodimethane on pentanol-ester functionalized SWCNTs [34]. 

Diels-Alder reaction of 3-vinylindole 131 with aryne in the presence of air gives, besides primary Diels-Alder product 132, the methyl 12-methyl-12H-[3]-benzoxepino[l,2-l7]indole-5-carboxylate 135. This can be explained by the formation of 1,2-dioxetane 133, its cyclo reversion and final intramolecular cyclization of dienol 134 or its tautomers (Scheme 26 (1996JCS(P1)1767)). 

There are a few reports of hetero-Diels-Alder Reactions promoted by LPDE. Intriguing stereoselectivity is observed for the [4 + 2] cyclization between Danishefsky s diene 77 and a-heteroatom-substituted aldehydes. For example, reaction of 77 with N-Boc-protected a-aminoaldehyde with 76 gave the threo isomer selectively, a result in keeping with a chelation-controUed process. In contrast, the threo diastereoselectivity observed could be reversed by changing the amino protecting group from A-Boc to A,A(-dibenzyl. In this instance, the erythro isomer was generated exclusively via a non-chelation-controlled transition state (Sch. 38) [89]. 

Precomplexation of a,/ -unsaturated ketone 163 with ATPH in CH2CI2 at -78 °C, then cyclization with cyclopentadiene, resulted in the stereochemical reversal to furnish exo-164 as a major product, as shown in Sch. 128. Similarly, the Diels-Alder reaction with other dienophiles complexed with ATPH resulted in exo selectivity [168],... 

This mechanism is, however, difficult to apply to the fast cycloaddition of diazoacetates (Alder et al., 1931) and 3-diazobutane-2-one (Diels and Konig, 1938) with alkenes of the bicyclo[2.2.1]heptene type, because alkene C-atoms without electron-withdrawing substituents show no electrophilic character. The reverse sequence of steps in (6-4), i. e., first an additon of N at the central C-atom of the acrylate, would also be unusual, as the N ()ff)-atom of diazoalkanes is only a weak electrophilic center. Fleischmann (in Huisgen s group, 1958) showed that, in such cyclization reactions, the rate of reaction of diazomethane with bicyclic alkenes relative to that of )ff-diazo ketones and 2-diazo-l,3-diketones is higer by a factor of 10" -10. ... 

---