RESUMEN

Herein, a SnCl4 -catalyzed intramolecular, interrupted homo-Nazarov cascade biscyclization to access angular (hetero)aryl-fused polycycles is reported. Subsequent decarboxylation of the readily enolizable products afforded the angular products in up to 71 % yield over two steps, with the trans-diastereomers as the major products. The cyclopropyl homo-Nazarov cyclization precursors were formed using a scalable and modular synthetic route that, ultimately, offers access to 6,6,6-, 6,6,5-, 6,5,6-, 6,6,5,6-, and 6,6,6,5-fused angular polycyclic products. To showcase the rigor and utility of the method, an 8-step total synthesis of (±)-1-oxoferruginol, an antibacterial aromatic abietane diterpenoid, was disclosed.

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RESUMEN

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.

RESUMEN

The first examples of a Lewis-acid catalyzed (hetero)arene interrupted, formal homo-Nazarov cyclization have been disclosed. Using SnCl4 as the catalyst, alkenyl cyclopropyl ketones undergo ring-opening cyclization to form six-membered cyclic oxyallyl cations. Subsequent intermolecular Friedel-Crafts-type arylation with various electron-rich arenes and heteroarenes provides functionalized α-(hetero)arylated cyclohexanones, a scaffold present in many natural products and bioactive compounds, in yields up to 88% and diastereomeric ratios up to 12:1. Regiospecific arylation occurs at the α-carbon of the oxyallyl cation due to polarization caused by the ester group.

RESUMEN

A chemodivergent, Lewis acid catalyzed allylsilane interrupted formal homo-Nazarov cyclization is disclosed. With catalytic amounts of SnCl4 and in the presence of allyltrimethylsilane, a formal Hosomi-Sakurai-type allylation of the oxyallyl cation intermediate is observed. A variety of functionalized donor-acceptor cyclopropanes and allylsilanes were shown to be amenable to the reaction transformation and the allyl products were formed in up to 92% yield. Under dilute reaction conditions with stoichiometric SnCl4 and at reduced temperatures, an unusual formal [3 + 2]-cycloaddition between the allylsilane and the oxyallyl cation occurred to give hexahydrobenzofuran products in up to 69% yield.

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