Switching Diastereoselectivity in Proline-Catalyzed Aldol Reactions

The choice of the anion of an achiral TBD-derived guanidinium salt, used as cocatalyst for proline, allows reacting cycloketones with aromatic aldehydes and preparing either <i>anti</i>- or <i>syn</i>-aldol adducts with very high enantioselectivity. As a proof of principle, we show how the judicious choice of an additive allows individual access to all possible products, thus controlling the stereochemical outcome of the asymmetric aldol reaction. The origin of the <i>syn</i> diastereoselectivity unfolds from an unusual equilibrium process coupled to the enamine-based catalytic cycle standard for proline