Despite extensive efforts by many practitioners in the field, methods for the direct a-C À H bond functionalization of unprotected alicyclic amines remain rare. A new advance in this area utilizes N-lithiated alicyclic amines. These readily accessible intermediates are converted to transient imines through the action of a simple ketone oxidant, followed by alkylation with a b-ketoacid under mild conditions to provide valuable b-amino ketones with unprecedented ease. Regioselective a'-alkylation is achieved for substrates with existing asubstituents. The method is further applicable to the convenient one-pot synthesis of polycyclic dihydroquinolones through the incorporation of a S N Ar step.
While numerous studies pertaining to the total synthesis of Cephalotaxus alkaloids have been reported, only two strategies have been reported to date for the successful synthesis of the C‐11 oxygenated subset, due to the additional synthetic challenge posed by the remote C‐11 stereocenter. Herein, we report the collective asymmetric total synthesis of C‐11 oxygenated Cephalotaxus alkaloids using a chiral proline both as a starting material and as the only chirality source. A tetracyclic advanced intermediate was synthesized in a highly stereoselective manner from l‐proline in 8 steps involving sequential chirality transfer steps such as a diastereoselective N‐alkylation, stereospecific Stevens rearrangement and intramolecular Friedel–Crafts reaction via an unusual O‐acyloxocarbenium intermediate. From a common intermediate, the asymmetric total synthesis of six C‐11 oxygenated Cephalotaxus alkaloids was completed by a series of oxidation state adjustments.
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