Intramolecular Aldol Reaction Starting from Dialdehydes

3 Intramolecular Aldol Reaction Starting from Dialdehydes 

In conclusion, there have been many reports of the high synthetic potential of the intramolecular aldol reaction in the enantioselective construction of cyclic enones. In particular the proline-catalyzed desymmetrization of triketones has been widely used for formation of optically active bicyclic systems which are versatile building blocks for steroids and other biologically active compounds. 

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The Hajos-Parrish-Eder-Sauer-Wiechert synthesis (Scheme 5) was the first example of an intramolecular proline-catalyzed asymmetric aldol reaction. Systematically, this reaction can be described as a 6-enolendo cyclization. In 2003, List et al. described the first example of an intramolecular enolexo aldolization 85). This approach was then used by Pearson and Mans for the synthesis of (-i-)-cocaine 92, starting from the weso-dialdehyde 90 on treatment with (S)-12 86). This desymmetrization process gave 91 as a mixture of epimers with good enantio-selectivity. The tropane skeleton 91 could be further transformed into +)-92 by conventional means (Scheme 21). 

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