Catalytic Enantioselective Perezone-Type [5 + 2] Cycloaddition

催化对映选择性哌嗪型[5+2]环加成反应

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Abstract

Here we report the first catalytic enantioselective Perezone-type [5 + 2] cycloaddition, enabling convenient access to a variety of bicyclo[3.2.1]octanes and other complex carbocycles from readily available quinone ketals and alkenes. Enabled by a new chiral squaramide catalyst, intermolecular C-C bond formation was achieved with excellent enantio- and diastereoselectivities. The highly enantioenriched and densely functionalized products can be transformed into diverse intriguing complex carbocycles that may not be straightforward to access by conventional methods. Mechanistic studies and DFT studies provided important insights into the mechanism, in which substrate solvation is a rate-limiting step, while C-C bond formation is fast and stepwise. Activation of the Lewis acid TESOTf by the chiral hydrogen bond donor catalyst is crucial not only for substrate activation and solvation but also for enantiocontrol via the catalyst-bound chiral counter anion.

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