Enantioselective Total Synthesis of 3β‐Hydroxy‐7β‐kemp‐8(9)‐en‐6‐one, a Diterpene Isolated from Higher Termites

Wang, Yuzhou; Jäger, Anne; Грүнер, Маргит; Lübken, Tilo; Metz, Peter

doi:10.1002/anie.201708561

Cited by 24 publications

(14 citation statements)

References 59 publications

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“…Metz and coworkers found use of our method for the synthesis of 3β-hydroxy-7β-kemp-8(9)-en-6-one. 35 In contrast, rhodium-catalyzed isomerization leads to the conjugated olefin. 36…”

Section: Isomerization Cycloisomerization and Retrocycloisomerizationmentioning

confidence: 99%

The High Chemofidelity of Metal-Catalyzed Hydrogen Atom Transfer

et al. 2018

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CONSPECTUS. Implementation of any chemical reaction in a structurally complex setting (King, S. M., J. Org. Chem., 2014, 79, 8937) confronts structurally-defined barriers: steric environment, functional group reactivity, product instability, and through-bond electronics. But there are also practical barriers. Late stage reactions conducted on small quantities of material are run inevitably at lower than optimal concentrations. Access to late stage material limits extensive optimization. Impurities from past reactions can interfere, especially with catalytic reactions. Therefore, chemical reactions that can be relied upon at the front lines of a complex synthesis campaign emerge from the crucible of total synthesis as robust, dependable, and widely applied. Trost conceptualized ‘chemoselectivity’ as a reagent’s selective reaction of one functional group or reactive site in preference to others (Trost, B. M., Science, 1983, 219, 245). Chemoselectivity and functional group tolerance can be evaluated quickly using robustness screens (Collins, K. D., Nat. Chem., 2013, 5, 597). A reaction may also be characterized by its ‘chemofidelity’, its reliable reaction with a functional group in any molecular context. For example, ketone reduction by an electride (dissolving metal conditions) exhibits high chemofidelity, but low chemoselectivity: it usually works, but many other functional groups are reduced at similar rates. Conversely, alkene coordination chemistry effected by π Lewis acids can exhibit high chemoselectivity (Trost, B. M., Science, 1983, 219, 245), but low chemofidelity: it can be highly selective for alkenes, but sensitive to substitution patterns (Larionov, E., Chem Comm., 2014, 50, 9816). In contrast, alkenes undergo reliable, robust, and diverse hydrogen atom transfer reactions from metal hydrides to generate carbon-centered radicals. Although there are many potential applications of this chemistry, its functional group tolerance, high rates, and ease of execution have led to its rapid deployment in complex synthesis campaigns. Its success derives from high chemofidelity; its dependable reactivity in many molecular environments and with many alkene substitution patterns. Metal hydride H-atom transfer (MHAT) reactions convert diverse, simple building blocks to more stereochemically and functionally dense products (Crossley, S. W. M., Chem. Rev., 2016, 116, 8912). When hydrogen is returned to the metal, MHAT can be considered the radical equivalent of Brønsted acid catalysis—itself a broad reactivity paradigm. This Account summarizes our group’s contributions to method development, reagent discovery, and mechanistic interrogation. Our earliest contribution to this area—a stepwise hydrogenation with high chemoselectivity and high chemofidelity—has found application to many problems. More recently, we reported the first examples of a dual-catalytic cross-couplings that rely on the merger of MHAT cycles and nickel catalysis. With time, we anticipate MHAT will become a staple of chemical synthesis.

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“…Metz and coworkers found use of our method for the synthesis of 3β-hydroxy-7β-kemp-8(9)-en-6-one. 35 In contrast, rhodium-catalyzed isomerization leads to the conjugated olefin. 36…”

Section: Isomerization Cycloisomerization and Retrocycloisomerizationmentioning

confidence: 99%

The High Chemofidelity of Metal-Catalyzed Hydrogen Atom Transfer

et al. 2018

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“…In contrast to the long multistep approaches reported by Paquette and Deslongchamps for the construction of the tetracyclic core of these terpenes, 185 Metz and co-workers reported the preparation of this polycyclic system in one step and in excellent yield from the dienyne 362 (Scheme 44), which was prepared from the Wieland-Miescher ketone in 20 steps. 186 Thus, exposure of 362 to the Grubbs II catalyst (4) afforded the tetracyclic de-rivative 363 in an astonishing 97% yield. Whereas the reduction of the resulting tetracyclic ketone 363 with L-Selectride provided the alcohol 364 with the opposite stereochemistry to that of the natural product, reduction of the bicyclic ketone precursor 362 provided the correct diastereomer 365 under the same reduction conditions.…”

Section: Scheme 43 Total Synthesis Of Englerin Amentioning

confidence: 99%

Recent Advances in Total Synthesis via Metathesis Reactions

Cheng-Sánchez

Sarabia

2018

Synthesis

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The metathesis reactions, in their various versions, have become a powerful and extremely valuable tool for the formation of carbon–carbon bonds in organic synthesis. The plethora of available catalysts to perform these reactions, combined with the various transformations that can be accomplished, have positioned the metathesis processes as one of the most important reactions of this century. In this review, we highlight the most relevant synthetic contributions published between 2012 and early 2018 in the field of total synthesis, reflecting the state of the art of this chemistry and demonstrating the significant synthetic potential of these methodologies.1 Introduction2 Alkene Metathesis in Total Synthesis2.1 Total Synthesis Based on a Ring-Closing-Metathesis Reaction2.2 Total Synthesis Based on a Cross-Metathesis Reaction2.3 Strategies for Selective and Efficient Metathesis Reactions of Alkenes2.3.1 Temporary Tethered Ring-Closing Metathesis2.3.2 Relay Ring-Closing Metathesis2.3.3 Stereoselective Alkene Metathesis2.3.4 Alkene Metathesis in Tandem Reactions3 Enyne Metathesis in Total Synthesis3.1 Total Syntheses Based on a Ring-Closing Enyne-Metathesis Reaction3.2 Total Syntheses Based on an Enyne Cross-Metathesis Reaction3.3 Enyne Metathesis in Tandem Reactions4 Alkyne Metathesis in Total Synthesis4.1 Total Synthesis Based on a Ring-Closing Alkyne-Metathesis Reaction4.2 Other Types of Alkyne-Metathesis Reactions5 Conclusions

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“…In 2017, Metz's group (Wang Y. et al, 2017) reported the first total synthesis of 3β-hydroxy-7β-kemp-8(9)-en-6-one, a diterpene with 5/6/6/7-fused tetracyclic kempane scaffold ( Figure 2A). The key step of this synthesis is a domino RCM from a dienyne-tethered Wieland-Miescher ketone using Grubbs II catalyst, which enables one-pot construction of two fused rings.…”

Section: Construction Of Polycyclic Carbocyclesmentioning

confidence: 99%

Recent Advances in Construction of Polycyclic Natural Product Scaffolds via One-Pot Reactions Involving Alkyne Annulation

Zheng

Hua

2020

Front. Chem.

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Polycyclic scaffolds are omnipresent in natural products and drugs, and the synthetic strategies and methods toward construction of these scaffolds are of particular importance. Compared to simple cyclic ring systems, polycyclic scaffolds have higher structure complexity and diversity, making them suitable for charting broader chemical space, yet bringing challenges for the syntheses. In this review, we surveyed progress in the past decade on synthetic methods for polycyclic natural product scaffolds, in which the key steps are one-pot reactions involving intermolecular or intramolecular alkyne annulation. Synthetic strategies of selected polycyclic carbocycles and heterocycles with at least three fused, bridged, or spiro rings are discussed with emphasis on the synthetic efficiency and product diversity. Recent examples containing newly developed synthetic concepts or toolkits such as collective and divergent total synthesis, gold catalysis, C-H functionalization, and dearomative cyclization are highlighted. Finally, several "privileged synthetic strategies" for "privileged polycyclic scaffolds" are summarized, with discussion of remained challenges and future perspectives.

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Enantioselective Total Synthesis of 3β‐Hydroxy‐7β‐kemp‐8(9)‐en‐6‐one, a Diterpene Isolated from Higher Termites

Cited by 24 publications

References 59 publications

The High Chemofidelity of Metal-Catalyzed Hydrogen Atom Transfer

The High Chemofidelity of Metal-Catalyzed Hydrogen Atom Transfer

Recent Advances in Total Synthesis via Metathesis Reactions

Recent Advances in Construction of Polycyclic Natural Product Scaffolds via One-Pot Reactions Involving Alkyne Annulation

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