Site-Selective Calcium-Catalyzed/Organocatalyzed Condensation of Propargyl Alcohols Tethered to β-Keto Esters.

The intramolecular condensation of -keto esters to give propargyl alcohols is described. The substrates have two electrophilic sites and two nucleophilic sites. The site selectivity can be fully controlled. In the presence of a calcium-based catalyst and under anhydrous conditions, O-addition products are isolated. On the other hand, traces of water or iPrOH as additive encourage calcium-catalyzed Meyer-Schuster rearrangements. The resulting enones may be further transformed into endo- Michael addition products. The regioselectivity of the attack of the enolate can be changed by using 1-[3,5-bis(trifluoromethyl) phenyl]-3-[2-(dimethylamino)cyclohexyl]thiourea (TUC) as organocatalyst, which promotes the formation of aldol-condensation products of high synthetic interest. DFT calculations rationalize the preference for the aldol condensation when TUC is used instead of the endo-Michael addition. [ABSTRACT FROM AUTHOR]