Iron-Catalyzed Hydrobenzylation: Stereoselective Synthesis of (−)-Eugenial C

Gan, Xu-cheng; Kotesova, Simona; Castanedo, Alberto; Green, Samantha A.; Møller, Søren Lau Borcher; Shenvi, Ryan A.

doi:10.1021/jacs.3c05428

Cited by 25 publications

(21 citation statements)

References 80 publications

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“…In this case, efficient conversion relied on the combined use of manganese and nickel. Consistent with prior work, 1,40 we suspect that nickel promotes the conversion of the alkyl iodide to the corresponding radical en route to alkylnickel formation and capture by the tertiary radical produced by MHAT. Thus, Co-, Fe-, and Mn-catalyzed MHAT could be leveraged in Csp 2 − Csp 3 and Csp 3 −Csp 3 cross-coupling reactions that benefited from the remarkable mildness of first-row transition-metal catalysis.…”

Section: Alkene Hydrofunctionalizations By Outer-sphere Cross-couplingsupporting

confidence: 89%

“…Chem. Soc.20231451571415720 Catalytic hydrogen atom transfer to alkenes: a roadmap for metal hydrides and radicalsShevickS.…”

Section: Key Referencesmentioning

confidence: 99%

“…Our proposal for the synthesis of meroterpenoid (−)-eugenial C ( 1 ) was married to the development of two generations of hydroalkylation methods , as well as the potential for these methods to interrogate the biological function of its two lobes . Biosynthetic reactions forge the unique bilobal structure of (−)-eugenial C convergently through Friedel–Crafts capture of a phloroglucinolmethyl cation reaction by bicyclogermacrene, followed by carbocationic rearrangement (Figure , top left) .…”

Section: Eugenial C Via Mhat/sh2: Two Outer-sphere Steps For Alkene H...mentioning

confidence: 99%

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Inner- and Outer-Sphere Cross-Coupling of High F_sp3 Fragments

Kotesova,

Shenvi

2023

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Natural product research originates from a desire to explore, understand, and perturb biological function with atomic precision. To reach these goals at all, let alone efficiently, requires thoughtful and creative problem solving. Often this means bold disconnections that would simplify access to complex structures, if only the methods existed to bridge these theoretical gaps. Whereas biological interrogations provide long-term intellectual value and impetus, methods come as attractive fringe benefits of natural product synthesis. This Account describes strategic, methodological solutions to the syntheses of natural products [(−)-eugenial C, Galbulimima alkaloids GB18, GB22, GB13, and himgaline] featuring new, convergent disconnections as important problemsolving steps, which themselves were inspired by recent methods that arose from our group. Each target required the invention of first-row transition metal-catalyzed cross-coupling procedures to satisfy the biological goals of the project. In these cases, synthetic strategy identified the methodological gap (the absence of stereoand chemoselective couplings of appropriate fragments), but the tactical advantage conferred by first-row metals met the challenge. These methods were competent to handle the dense, sterically encumbered motifs common to natural products due to, in many cases, elementary steps that did not require bond formation between the hindered substrate and the metal center. Instead, these sterically lenient reactions appeared to involve metal−ligand−substrate reactions (i.e., outer-sphere steps), in contrast to the metal− substrate, coordinative reactions of precious metals (i.e., inner-sphere steps). Key observations from our previous studies, combined with the observations in seminal publications from other laboratories (Mattay, Weix, and MacMillan), led to the optimization of ligand-controlled, stereoselective reactions and the introduction of complementary catalytic cycles that revealed new modes of reactivity and generated novel structural motifs. Optimized access to bioactive natural product space accelerated our timeline of biological characterization, fulfilling a common premise of natural products research. The integration of methodology, complex natural product synthesis, diversification, and bioassay into a single Ph.D. dissertation would have been unmanageable in a prior era.The unique ability of first-row transition metals to effect Csp 3 −Csp 3 cross-coupling with high chemo-and stereoselectivity has significantly lowered the barrier to reach the avowed goal of natural product synthesis and reduced the burden (real or perceived) of integrating natural products into functional campaigns.

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Section: Alkene Hydrofunctionalizations By Outer-sphere Cross-couplingsupporting

confidence: 89%

“…Chem. Soc.20231451571415720 Catalytic hydrogen atom transfer to alkenes: a roadmap for metal hydrides and radicalsShevickS.…”

Section: Key Referencesmentioning

confidence: 99%

Section: Eugenial C Via Mhat/sh2: Two Outer-sphere Steps For Alkene H...mentioning

confidence: 99%

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Inner- and Outer-Sphere Cross-Coupling of High F_sp3 Fragments

Kotesova,

Shenvi

2023

Acc. Chem. Res.

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“…As an alternative, our proposed tactic relied on metal catalysed hydrogen atom transfer (MHAT) catalysis whereby a cobalt catalyst could selectively transfer a hydrogen atom to an unsaturated CÀ C bond. [22][23][24] We hypothesised that generation of this key cobalt hydride species under a photoinduced, reductive regime might allow us to pair this with reductive generation of a second radical, [25][26][27][28][29] ultimately leading to selective, sterically controlled coupling based on the persistent radical effect (Scheme 1c). [30] For the heteroarene synthon, we sought to exploit pyridyl phosphonium salts, easy-to-synthesise precursors which have been extensively researched by McNally and co-workers over the last years.…”

Section: Introductionmentioning

confidence: 99%

Photoinduced Cobalt Catalysis for the Reductive Coupling of Pyridines and Dienes Enabled by Paired Single‐Electron Transfer**

Qin,

Barday,

Jana

et al. 2023

Angew Chem Int Ed

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Selective hydroarylation of dienes has potential to provide swift access to useful building blocks. However, most existing methods rely on dienes stabilised by an aromatic group and transmetallation or nucleophilic attack steps require electron‐rich aryl coupling partners. As such, there are few examples which tolerate wide‐spread heteroarenes such as pyridine. Whilst allylic C–H functionalisation could be considered an alternative approach, the positional selectivity of unsymmetrical substrates is hard to control. Here, we report a general approach for selective hydropyridylation of dienes under mild conditions using metal catalysed hydrogen‐atom transfer. Photoinduced, reductive conditions enable simultaneous formation of a cobalt‐hydride catalyst and the persistent radical of easily‐synthesised pyridyl phosphonium salts. This facilitates selective coupling of dienes in a traceless manner at the C4‐position of a wide‐range of pyridine substrates. The mildness of the method is underscored by its functional group tolerance and demonstrated by applications in late‐stage‐functionalization. Based on a combination of experimental and computational studies, we propose a mechanistic pathway which proceeds through non‐reversible hydrogen atom transfer from a cobalt hydride species which is uniquely selective for dienes in the presence of other olefins due to a much higher relative barrier associated with olefin hydrogen‐atom‐transfer (HAT).

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“…3a Fe mediated MHAT C-C bond forming reactions, in particular, have been utilised in complex molecule synthesis. Some recent interesting examples include an intermolecular hydrobenzylation, 8 an intramolecular radical aryl cyclisation 9 and a cyclisation with an enol radical acceptor. 10 It is noteworthy that these C-C bond forming reactions proceed under mild conditions and are not affected by the presence of oxygen and water.…”

Section: Introductionmentioning

confidence: 99%