One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp3)–C(sp3) bonds, which requires using transition or precious metal catalysts. We present here an alternative: the deconstructive lactamization of piperidines without using transition metal catalysts. To this end, we use 3‐alkoxyamino‐2‐piperidones, which were prepared from piperidines through a dual C(sp3)–H oxidation, as transitory intermediates. Experimental and theoretical studies confirm that this unprecedented lactamization occurs in a tandem manner involving an oxidative deamination of 3‐alkoxyamino‐2‐piperidones to 3‐keto‐2‐piperidones, followed by a regioselective Baeyer–Villiger oxidation to give N‐carboxyanhydride intermediates, which finally undergo a spontaneous and concerted decarboxylative intramolecular translactamization.

One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp 3 )-C(sp 3 )b onds,w hich requires using transition or precious metal catalysts.W ep resent here an alternative:t he deconstructive lactamization of piperidines without using transition metal catalysts.T ot his end, we use 3-alkoxyamino-2-piperidones,w hich were prepared from piperidines through adual C(sp 3 )-H oxidation, as transitory intermediates.Experimental and theoretical studies confirm that this unprecedented lactamization occurs in at andem manner involving an oxidative deamination of 3-alkoxyamino-2-piperidones to 3keto-2-piperidones,f ollowed by ar egioselective Baeyer-Villiger oxidation to give N-carboxyanhydride intermediates, which finally undergo aspontaneous and concerted decarboxylative intramolecular translactamization.

Highlighting the recently established methodology for the direct synthesis of glycidic amides from tertiary allyl amines, the synthesis of the enantiomers of tedanalactam were completed in two steps from the corresponding chiral dihydropiperidine. Additionally, the (+)- and (-)-enantiomers of piplaroxide were obtained from their respective tedanalactam precursor, and the absolute configuration of the naturally occurring (+)-piplaroxide was determined. The present approach represents not only the shortest synthesis of (-)-tedanalactam but also the first total synthesis of (+)-piplaroxide, a repellent against the leafcutter ant Atta cephalotes.

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The general approach for accessing to a tetracyclic hexahydro‐3H‐indolizino[8,7‐b]indol‐3‐one alkaloids is that what involves the construction of the γ‐lactam ring from a tricyclic precursor. Here in this report, we disclose a new synthetic strategy that permits the direct deconstruction of the tetracyclic indolo[2,3‐a]quinolizine motif into the tetracyclic hexahydroindolizin‐3‐one scaffold of the naturally occurring (+)‐cuscutamine without the use of either transition or precious metals. Additionally, the current total synthesis of both enantiomers provides structural clarification of the natural occurring alkaloid.