α-Alkylidene-γ-butyrolactone Formation via Bi(OTf)3-Catalyzed, Dehydrative, Ring-Opening Cyclizations of Cyclopropyl Carbinols: Understanding Substituent Effects and Predicting E/Z Selectivity.

A Bi(OTf)3-catalyzed ring-opening cyclization of (hetero)aryl cyclopropyl carbinols to form α-alkylidene-γ-butyrolactones (ABLs) is reported. This transformation represents different chemoselectivity from previous reports that demonstrated formation of (hetero)aryl-fused cyclohexa-1,3-dienes upon acid-promoted cyclopropyl carbinol ring opening. ABLs are obtained in up to 89% yield with a general preference for the E-isomers. Mechanistically, Bi(OTf)3 serves as a stable and easy to handle precursor to TfOH. TfOH then catalyzes the formation of cyclopropyl carbinyl cations, which undergo ring opening, intramolecular trapping by the neighboring ester group, subsequent hydrolysis, and loss of methanol resulting in the formation of the ABLs. The nature and relative positioning of the substituents on both the carbinol and the cyclopropane determine both chemo- and stereoselective outcomes. Carbinol substituents determine the extent of cyclopropyl carbinyl cation formation. The cyclopropane donor substituents determine the overall reaction chemoselectivity. Weakly stabilizing or electron-poor donor groups provide better yields of the ABL products. In contrast, copious amounts of competing products are observed with highly stabilizing cyclopropane donor substituents. Finally, a predictive model for E/Z selectivity was developed using DFT calculations.

Calcium-Catalyzed, Dehydrative, Ring-Opening Cyclizations of Cyclopropyl Carbinols Derived from Donor-Acceptor Cyclopropanes.

A calcium-catalyzed, dehydrative, ring-opening cyclization of (hetero)aryl cyclopropyl carbinols is reported. The cyclopropyl carbinols are prepared directly from the corresponding donor-acceptor (D-A) cyclopropanes. The calcium catalyst catalyzes the formation of putative (hetero)aryl cyclopropyl carbinyl cations that undergo ring-opening to allylcarbinyl cations. Subsequent intramolecular Friedel-Crafts reaction affords (hetero)aryl-fused cyclohexa-1,3-dienes in up to 97% yield. This approach represents the first example of catalysis for this intramolecular, dehydrative ring-opening cyclization and outperforms the previous reports using stoichiometric Lewis acids.

Rh(I)-catalyzed chemo- and stereoselective domino cycloaddition of optically active propargyl 2,4-hexadienyl ethers.

1,1'-Bi-2-naphthol in combination with ZnEt2, Ti(O(i)Pr)4, and dicyclohexylamine have been employed to catalyze asymmetric alkyne addition to an ynal to synthesize optically active propargylic alcohols containing two alkyne functions with excellent yields and enantioselectivities. These chiral alcohols are readily converted to the corresponding optically active propargyl 2,4-hexadienyl ethers. These diene-diyne substrates are found to undergo a highly chemoselective and stereoselective domino Pauson-Khand and Diels-Alder cycloaddition catalyzed by [RhCl(CO)2]2 under CO to generate a class of tetracyclic compounds with high enantiomeric purity. This is a very efficient method for the asymmetric synthesis of polycyclic compounds.