Enantio‐ and Diastereodivergent Sequential Catalysis Featuring Two Transition‐Metal‐Catalyzed Asymmetric Reactions

This study demonstrates the feasibility and inherent benefits of combining two distinct asymmetric transition‐metal‐catalyzed reactions in one pot. The reported transformation features a Pd‐catalyzed asymmetric allylic alkylation and a Rh‐catalyzed enantioselective 1,4‐conjugate addition, effectively converting simple allyl enol carbonate precursors into enantioenriched cyclic ketones with two remote stereocenters. Despite the anticipated challenges associated with controlling stereoselectivity in such a complex system, the products are obtained in enantiomeric excesses ranging up to >99 % ee, exceeding those obtained from either of the individual asymmetric reactions. In addition, since the stereoselectivity of both steps is under catalyst control, this one‐pot reaction is enantio‐ and diastereodivergent, enabling facile access to all stereoisomers from the same set of starting materials. Two chiral transition‐metal catalysts are combined in one pot to perform orthogonal asymmetric transformations. Simple allyl enol carbonates are converted to ketones bearing two non‐contiguous stereogenic centers via a Pd‐catalyzed asymmetric allylic alkylation followed by a Rh‐catalyzed enantioselective Hayashi–Miyaura conjugate addition. This sequential catalysis process is enantio‐ and diastereodivergent and exhibits statistical amplification of enantiomeric excess.