The Diels-Alder Approach

The synthesis of macropolycyclic arrays — both linear and cyclic — and their derivatives is an area of growing current interest since it provides compounds of considerable academic and technological interest [39]. Although several different synthetic strategies can be envisaged for the production of polyacene and cyclacene derivatives, none have surpassed the utilization of pericyclic reactions, most notably the Diels-Alder cycloaddition, for the construction [40] of the laterally-fused six-membered ring backbone. 

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Scheme 7.8. The Diels-Alder approach to oseltamivir phosphate (1).

Naphthoquinone derivatives are excellent precursors for many types of angucyclines, particularly in the Diels-Alder approach (see above). Consequently, naphthols, which can easily be oxidized to naphthoquinones, have often been selected as the starting materials for the attachment of the C-glycosidic part [137]. 

Pearson and Ong86 have extended their route to trichothecane sesquiterpenoids via organoiron complexes by the synthesis of (144) (Scheme 14). The Diels-Alder approach to the construction of the cw-fused AB ring junction of the tricho-thecanes has been much in evidence. The use of methyl coumalate (145) as a... 

The Diels-Alder approach to bicyclo[2.2.1]heptanes is still giving rise to much work. We might mention the catalysis of the reaction between... 

Cydopentadietie (11) is also readily available so that the Diels-Alder approach is particularly suitable for compounds with the skeleton (12)—a common skeleton in many natural products. 

Adoption of the Diels-Alder approach depicted requires that the eventual C(9) configuration be inverted at some point in the synthesis and that the six-member B ring undergo ring contraction. Prior to addressing these two issues, the hydroxyl group in (302) was protected [TBDPSC1, imidazole, DMF, 70%] as its tert-butyldiphenylsilyl ether (303). 

Shiramizu, M. and Toste, F.D. (2011) On the diels-alder approach to solely biomass-derived polyethylene terephthalate (PET) Conversion of 2,5-dimethylfuran and acrolein into p-Xylene. Chemistry A European Journal, 17 (44), 12452-12457. 

The synthesis of Eschenmoser (Scheme 11.11) took its start with an easily accessible compound, purpurogallin, which has a benzo-anellated seven-membered ring system (incidentally, a tropolone system as well). The main challenge was the position-specific anellation of the second seven-membered ring. The Diels-Alder approach chosen required the presence of two ester groups (Add EG), that had to be subsequently removed. The tropolone arrived at in this manner had unfortunately an incorrect placement of oxygen... 

With this compound in hand, attempts could now begin to examine the viability of the Diels—Alder approach to cast the bicyclic [4.3.1] core of the CP-molecules. Fortunately, preliminary probes of the reaction using Me2AlCl as a catalyst in CH2CI2 at — 10°C... 

SCHEME 1 Retrosynthesis and retrobiosynthesis the Diels-Alder approach presents itself. 

Separation schemes for 27-30 were developed. Materials were advanced using methodology related to that described In the DIels-Alder approach. Whereas this synthesis appears to be shorter, it Is truly stereorandom. The upside Is that It provided stereoisomers for biological evaluation. 

Over the last decade, considerable progress has been reported in the synthesis of arenes following the Diels-Alder approach for the synthesis of dihydroaromatic intermediates of type 1. These intermediates themselves represent highly interesting building blocks, and in several investigations the oxidation of 1 was not the prime focus. Accordingly, we also cover reactions for the synthesis of dihydroaromatic products of type 1. 

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