text: To date, there have been few examples of hydrogen-bond catalysis in the synthesis of natural products despite the large number of reactions being discovered. Generally, with high required catalyst loading and often extreme substrate specificity, hydrogen-bond catalysis is not yet developed enough to provide useful, general reactions that represent a significant improvement over traditional methods. In the published examples, hydrogen-bond catalysis is mainly used in the beginning stages to quickly access early intermediates with high enantiomeric enrichment.
  In the Jacobsen synthesis of (+)-yohimbine, an indole alkaloid, an early enantioselective Pictet-Spengler reaction using a pyrrole-substituted thiourea catalyst produced gram-scale quantities of product in 94% ee and 81% yield. The remainder of the synthesis was short, using a reductive amination and an intramolecular Diels-Alder reaction.
  In 2008, Takemoto disclosed a concise synthesis of (−)-epibatidine that relied on a Michael cascade, catalyzed by a bifunctional catalyst. After initial asymmetric Michael addition to the β-nitrostyrene, intramolecular Michael addition furnishes the cyclic ketoester product in 75% ee. Standard functional group manipulations and an intramolecular cyclization yields the natural product.