Isosteviol?Proline Conjugates as Highly Efficient Amphiphilic Organocatalysts for Asymmetric Three-Component Mannich Reactions in the Presence of Water

In this work, six isosteviol?amino acid conjugates were designed and synthesized through simple condensation on a large scale without protecting group (Scheme). These amphiphilic organocatalysts mediated asymmetric three-component Mannich reactions of cyclohexanone and anilines with aromatic aldehydes in the presence of H2O. Meanwhile, the isosteviol?proline conjugate 3b has been established as a highly efficient catalyst (Table 1), and afforded syn-Mannich products with excellent diastereoselectivities (syn/anti up to 98?:?2) and enantioselectivities (up to >99% ee; Table 3). The transition state of the reaction in the presence of H2O is proposed (Fig. 2).