Ligand Effects in Regio‐ and Enantioselective Cobalt‐Catalyzed Intramolecular [4+2]‐ and [2+2]‐Cycloaddition Reactions of Unactivated 1,3‐Diene‐8‐ynes and 1,3‐Diene‐8‐enes

Intramolecular Diels-Alder reactions have been extensively used for the syntheses of biologically active compounds including natural products. We have identified Co(I) complexes and optimal reaction conditions to accomplish highly diastereo- and enantioselective intramolecular [4+2]-cycloaddition reactions of 1,3-diene-ynes and 1,3-diene-enes. These catalysts, readily prepared from an earth-abundant metal and tunable ligands, serve as practical replacements for the prohibitively expensive Rh-complexes previously used for similar reactions. The cationic complexes are readily prepared by the reaction of LCoX₂ with Zn in the presence of NaBARF. Both neutral and cationic Co(I)-complexes of (S)-BINAP and (S)-H₈-BINAP ligands effect the cyclization of 1,3-diene-ynes giving the expected [4+2]-addition products in excellent selectivities. The [4+2]-cycloadditions of the less reactive 1,3-diene-enes proceed only with the cationic complexes and 1,2-bis-[(2S,5S)-2,5-diphenylphospholan-1-yl]ethane (PhBPE) and appropriately substituted phosphinooxazoline (PHOX) are the most optimal ligands for these reactions. Depending on the ligands, 1,3-diene-enes bearing an aromatic substituent at the terminal position undergo an intramolecular [2+2]-cycloaddition, giving cyclobutane products in very good yields and enantioselectivities. The absence of the corresponding [2+2]-cycloaddition in the 1,3-diene-yne substates may be related to the enhanced strain in the expected bicyclo[3.2.0]heptene products. A unified mechanism involving Co(I)/Co(III)-redox cycle, consistent with all available evidence, is proposed for these reactions.