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DOI: 10.1055/s-0033-1341116
Diels–Alder/Lactonization Cascade Reactions
Publication History
Publication Date:
17 April 2014 (online)
Significance
Romo and co-workers report a cascade consisting of an organocatalyzed Diels–Alder reaction and lactonization. The authors identified isothiourea (–)-BTM as the optimal catalyst, which enabled the cascade to proceed with good to high yields and excellent stereoselectivities. It was demonstrated that the reaction can be rendered stereodivergent when the dienol substrate contains a racemic secondary alcohol function. The utility of the methodology was demonstrated in several formal syntheses of natural products. Finally, a stereochemical model was proposed and supported by a complementary computational study.
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Comment
The methodology presented relies on a LUMO-lowering activation, which is achieved through acylammonium ion formation. The authors demonstrate that, using this strategy, the combination of several organocatalyzed steps in a cascade reaction can be employed for the rapid generation of molecular complexity. Furthermore, the stereochemical model developed allows for the prediction of the absolute stereochemistry and the rationalization of substituent effects, which will greatly facilitate the implementation of this methodology in the synthesis of natural products and pharmaceutical targets.
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