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The rearrangement of carbon-carbon (C-C) single bonds in readily available carbocyclic scaffolds can yield uniquely substituted carbocycles that would be challenging to construct otherwise. This is a powerful and often non-intuitive approach for complex molecule synthesis. The transition-metal-mediated cleavage of C-C bonds has the potential to broaden the scope of this type of skeletal remodeling by providing orthogonal selectivities compared to more traditional pericyclic and carbocation-based rearrangements. To highlight this emerging technology, a unified, asymmetric, total synthesis of the phomactin terpenoids was developed, enabled by the selective C-C bond cleavage of hydroxylated pinene derivatives obtained from carvone. In this full account, the challenges, solutions, and intricacies of Rh(I)-catalyzed cyclobutanol C-C cleavage in a complex molecule setting are described. In addition, details of the evolution of strategies that ultimately led to the total synthesis of phomactins A, K, P, R, and T, as well as the synthesis and structural reassignment of Sch 49027, are given.

Saturated cyclic amines (aza-cycles) are ubiquitous structural motifs found in pharmaceuticals, agrochemicals, and bioactive natural products. Given their importance, methods that directly functionalize aza-cycles are in high demand. Herein, we disclose a fundamentally different approach to functionalizing cyclic amines which relies on C─C cleavage and attendant cross-coupling. The initial functionalization step is the generation of underexplored N-fused bicyclo α-hydroxy-β-lactams under mild, visible light conditions using a Norrish-Yang process to affect α-functionalization of saturated cyclic amines. This approach is complementary to previous methods for the C─H functionalization of aza-cycles and provides unique access to various cross-coupling adducts. In the course of these studies, we have also uncovered an orthogonal, base-promoted opening of the N-fused bicyclo α-hydroxy-β-lactams. Computational studies have provided insight into the origin of the complementary C─C cleavage processes.

Deconstructive functionalization involves carbon-carbon (C-C) bond cleavage followed by bond construction on one or more of the constituent carbons. For example, ozonolysis1 and olefin metathesis2,3 have allowed each carbon in C=C double bonds to be viewed as a functional group. Despite the substantial advances in deconstructive functionalization involving the scission of C=C double bonds, there are very few methods that achieve C(sp3)-C(sp3) single-bond cleavage and functionalization, especially in relatively unstrained cyclic systems. Here we report a deconstructive strategy to transform saturated nitrogen heterocycles such as piperidines and pyrrolidines, which are important moieties in bioactive molecules, into halogen-containing acyclic amine derivatives through sequential C(sp3)-N and C(sp3)-C(sp3) single-bond cleavage followed by C(sp3)-halogen bond formation. The resulting acyclic haloamines are versatile intermediates that can be transformed into various structural motifs through substitution reactions. In this way we achieve the skeletal remodelling of cyclic amines, an example of scaffold hopping. We demonstrate this deconstructive strategy by the late-stage diversification of proline-containing peptides.

Deconstructive functionalizations involving scission of carbon-carbon double bonds are well established. In contrast, unstrained C(sp3)-C(sp3) bond cleavage and functionalization have less precedent. Here we report the use of deconstructive fluorination to access mono- and difluorinated amine derivatives by C(sp3)-C(sp3) bond cleavage in saturated nitrogen heterocycles such as piperidines and pyrrolidines. Silver-mediated ring-opening fluorination using Selectfluor highlights a strategy for cyclic amine functionalization and late-stage skeletal diversification, establishing cyclic amines as synthons for amino alkyl radicals and providing synthetic routes to valuable building blocks.

Despite the widespread success in the functionalization of C(sp2)−H bonds, the deliberate functionalization of C(sp3)−H bonds in a highly site‐ and stereoselective manner remains a longstanding challenge. Herein, we report an iridium/aluminum cooperative catalytic system that enables the β‐selective C−H borylation of saturated cyclic amines and lactams. Furthermore, we have accomplished an enantioselective variant using binaphthol‐derived chiral aluminum catalysts to forge C−B bonds with high levels of stereocontrol. Computational studies suggest that the formation of a Lewis pair with the substrates is crucial to lower the energy of the transition state for the rate‐determining reductive elimination step. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess pacing during cross-country racing in relation to race length, surface-terrain and racing dynamics. Athletes (n = 148) competed for school teams (U15, U17, U20) over 2.9, 4.2, 6.3 km, respectively. The course lap (2.067 m) was timed using UHF-RFID and divided into six sections based on surface-terrain and length (549, 619, 207, 338, 150, 156m). Overall pace differed between races (4.56 ± 0.30, 4.42 ± 0.38, 4.40 ± 0.31 m∙s−1, p=0.042) but not for the top-20 of each race (p=0.174). Moreover, within lap pacing followed a repeated reverse-"J"-parabolic strategy for all races. Race length (no. of laps) and category affected pacing with regards to finish position banding (1st–10th, 11th–20th) where effect size differences showed large to extremely large (1.21 – >4.00) difference between top-10 and other bands. Exceptions to this included the finish sprint where it was typically trivial-moderate (<0.2–1.2) and in key areas where social facilitation occurred. Athlete/coaches need to be aware of between and within lap variations in pace/effort, the effects of race dynamics, and spectator influences, while all athletes need to be educated as part of their training to run their own optimal strategy for best performance. [ABSTRACT FROM AUTHOR]