Neighbouring group directed protonation in the Birch reduction of styrene double bonds

Lin, Zhen; Chen, Jinhua; Valenta, Z.

doi:10.1016/s0040-4039(97)00776-4

Cited by 5 publications

(2 citation statements)

References 4 publications

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“…This was based on the assumption that protonation of the initially formed radical anion would occur by syn -delivery of the proton from the homoallylic alcohol. There was precedent for this type of process; however, when the enone in entry 12 was subjected to the Birch conditions (Na, NH 3 , −78 °C) only trans -product was observed. This result implies that the carbanion intermediate was either very stable and did not abstract a proton until the methanol quench, which is unlikely, or that protonation from the solvent (NH 3 ) was more favorable and/or faster, or that protonation occurred intermolecularly.…”

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confidence: 99%

Construction of cis- and trans-Decahydroisoquinolines via Heterogeneous Catalytic Hydrogenation

1999

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confidence: 99%

Construction of cis- and trans-Decahydroisoquinolines via Heterogeneous Catalytic Hydrogenation

1999

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“…Despite a promising analysis, all homogeneous hydrogenations proceeded from the α-face. Additionally, several unconventional approaches for intramolecular hydrogen delivery, including tethered hydroboration, hydrosilylation ( 70 ), and directed Birch protonation ( 71 ) were all met with failure.…”

Section: First-generation Approach To Isomalabaricanes: Total Synthes...mentioning

confidence: 99%

Total Synthesis of Stelletins through an Unconventional Annulation Strategy

2021

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Conspectus Marine ecosystems present the largest source of biodiversity on the planet and an immense reservoir of novel chemical entities. Sessile marine organisms such as sponges produce a wide range of complex secondary metabolites, many of these with potent biological activity engineered for chemical defense. That such compounds exert dynamic effects outside of their native context is perhaps not surprising, and the realm of marine natural products has attracted considerable attention as a largely untapped repository of potential candidates for drug development. Only a handful of the more than 15 000 marine natural products that have been isolated to date have advanced to the clinic, and more are to be expected. The rich chemical information encoded in the intricate three-dimensional structures of many marine natural products facilitates highly discriminating interactions with cell signaling pathways, and especially within cancer cells such nuanced effects offer an exciting opportunity for the development of targeted therapies that lack the side effects and general toxicity of conventional chemotherapeutics. The isomalabaricanes are a rare class of marine triterpenoids that have been hailed as promising cytotoxic lead compounds for the treatment of cancer, and they have attracted a flurry of excitement from researchers because of their potent cytotoxicity in certain human cancer cell lines along with a range of other antineoplastic effects. Most notably, their inhibitory activity is highly cell-selective, characterized by large deviations from their mean GI50 concentrations across 3 orders of magnitude in the NCI-60 Human Tumor Cell Lines screen, suggesting mechanistic specificity rather than general and unbridled toxicity. Despite these auspicious preliminary reports, the isomalabaricane scaffold remains largely unexplored as a potential anticancer lead because of lack of material. This Account describes our recent efforts to develop a general, modular synthesis of the isomalabaricanes, as exemplified by the successful total syntheses of rhabdastrellic acid A, stelletin E, and stelletin A. The unorthodox trans-syn-trans configuration of their perhydrobenz[e]indene core severely circumscribes the synthetic methods available for its construction and required several generations of strategy to assemble. Ultimately, a series of unconventional transformations were identified that were capable of building this highly strained motif, and the syntheses of rhabdastrellic acid A and stelletin E were completed in racemic fashion. Subsequently, a second-generation approach to these natural products was developed, rendering the synthesis enantioselective as well as providing access to stelletin A. These synthetic efforts were greatly assisted by computational techniques such as 13C NMR prediction, which enabled structural assignments of hydrocarbon diastereomers, as well as relaxed surface scan conformational analysis, which informed a campaign for directed hydrogenation of an alkene. High-throughput experimentation met...

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Birch Reduction

2010

Comprehensive Organic Name Reactions and Reagents

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The reduction of aromatic compounds by alkali metal in liquid ammonia in the presence of alcohol is generally known as the Birch reduction or metal‐ammonia reduction. The Birch reduction uses the ammonia‐solvated electrons arising from alkali metal as the reducing agent, which bears the extremely negative single‐electron redox potential. Once the solvated electron adds to aromatic system, the radical anion is quenched by alcohol, so that cyclohexa‐1,4‐diene derivatives are often produced from benzene derivatives without further reduced species. It has been pointed out that the existing alkali metal also reacts with alcohol to generate hydrogen, in a reaction known as the hydrogen reaction. It has been reported that both the rate and yield of the Birch reduction decreases in the order of Li>Na>K. One of the advantages associated with the Birch reduction is its efficient steric control on the aromatic system. The applications of the Birch reduction are to convert aryl alkyl ethers into 1‐alkoxycyclohexa‐1,4‐dienes and also to reduce acetylenes stereospecifically to trans‐olefins and to hydrogenate graphite and carbon single‐walled nanotubes (SWNTs). The Birch reaction has also been found to cleave the CC bond in the presence of the aromatic system.

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Neighbouring group directed protonation in the Birch reduction of styrene double bonds

Cited by 5 publications

References 4 publications

Construction of cis- and trans-Decahydroisoquinolines via Heterogeneous Catalytic Hydrogenation

Construction of cis- and trans-Decahydroisoquinolines via Heterogeneous Catalytic Hydrogenation

Total Synthesis of Stelletins through an Unconventional Annulation Strategy

Birch Reduction

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