Transition metal (TM)-catalyzed carbon–carbon (C–C) bond activation has emerged as a useful tool for devising unusual bond-disconnecting strategies. (7) To seek a complementary ring-forming approach, a deconstructive strategy based on C–C bond activation of readily available cyclic ketones has been conceived (Scheme 1A). This named “cut-and-sew” strategy (8) uses cyclic ketones with a tethered unsaturated moiety as substrates. It starts with the oxidative addition of a TM into the ketone C–C bond (the “cut” step) to give a reactive metallacycle, followed by intramolecular migratory insertion of the unsaturated unit and reductive elimination to furnish the ring (the “sew” step). It has been hypothesized that, by changing the ring sizes of the cyclic ketones, the length of the linkers, and different unsaturated coupling partners, diverse bridged and fused ring scaffolds would be constructed by this unified method. In addition, considering that the carbonyl moiety in ketones can be extruded under certain conditions during the C–C activation processes, the decarbonylative cut-and-sew reactions (with CO deletion) can also be realized with ketone-based substrates. Moreover, apart from the normal 2π insertion, TM-catalyzed one-carbon ring expansions have also been achieved to generate intriguing products.

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On the basis of the rich prior knowledge of C–C activation, (7,9) our group has been exploring the TM-catalyzed cut-and-sew reactions and their applications in complex molecule synthesis since 2012. (1) In the past 10 years, benzocyclobutenones and cyclobutanones have been the two main classes of substrates we have studied. To date, several different types of cut-and-sew reactions with benzocyclobutenones and cyclobutanones have been developed in our laboratory, including (a) (4 + 2) or (4 + 2 – 1) cycloaddition between benzocyclobutenones and 2π units to construct [m.n.0] fused rings; (b) (4 + 1) cycloaddition between benzocyclobutenones and stryenes to construct 2-indanones; (c) (4 + 2) cycloaddition between α-branched cyclobutanones and 2π units to construct [m.n.0] fused rings; and (d) (4 + 2), (4 + 2 – 1), or (4 + 1) cycloaddition between β-branched cyclobutanones and 2π units to construct [m.n.1] bridged rings. To illustrate how these ring-forming methods can facilitate syntheses of complex molecules, these C–C activation methods have been applied to a number of concise total syntheses (Scheme 1B). (3,4,10) In this Account, we first summarize our development of these catalytic cut-and-sew methods with benzocyclobutenones and cyclobutanones, followed by discussions of streamlined syntheses of (−)-cycloclavine, (−)-thebainone A, penicibilaenes, and the proposed cycloinumakiol, as representative examples enabled by such a deconstructive strategy.