Unlocking Terpenoid Transformations: C–H Bond Functionalization for Methyl Group Substitution, Elimination, and Integration

InfoMetricsFiguresRef. ACS Central ScienceASAPArticle This publication is Open Access under the license indicated. Learn More CiteCitationCitation and abstractCitation and referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse First ReactionsOctober 11, 2024Unlocking Terpenoid Transformations: C–H Bond Functionalization for Methyl Group Substitution, Elimination, and IntegrationClick to copy article linkArticle link copied!Site-selective functionalization of methyl groups in terpenoid natural products.Lauren A. M. Murray*Lauren A. M. MurrayDepartment of Biochemistry, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia*Email: [email protected]More by Lauren A. M. Murrayhttps://orcid.org/0000-0003-3249-0828Open PDFACS Central ScienceCite this: ACS Cent. Sci. 2024, XXXX, XXX, XXX-XXXClick to copy citationCitation copied!https://pubs.acs.org/doi/10.1021/acscentsci.4c01569https://doi.org/10.1021/acscentsci.4c01569Published October 11, 2024 Publication History Published online 11 October 2024newsPublished 2024 by American Chemical Society. This publication is licensed under CC-BY 4.0 . License Summary*You are free to share (copy and redistribute) this article in any medium or format and to adapt (remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:Creative Commons (CC): This is a Creative Commons license.Attribution (BY): Credit must be given to the creator.View full license*DisclaimerThis summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials. This publication is licensed underCC-BY 4.0 . License Summary*You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below: Creative Commons (CC): This is a Creative Commons license. Attribution (BY): Credit must be given to the creator.View full license *DisclaimerThis summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials. License Summary*You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below: Creative Commons (CC): This is a Creative Commons license. Attribution (BY): Credit must be given to the creator. View full license *DisclaimerThis summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials. License Summary*You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below: Creative Commons (CC): This is a Creative Commons license. Attribution (BY): Credit must be given to the creator. View full license *DisclaimerThis summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials. ACS PublicationsPublished 2024 by American Chemical SocietySubjectswhat are subjectsArticle subjects are automatically applied from the ACS Subject Taxonomy and describe the scientific concepts and themes of the article.AlkylsFunctionalizationHydrocarbonsOxidationPharmaceuticalsTerpenoids are one of the largest classes of natural products, encompassing a diverse group of molecules with a wide variety of biological activities. (1) These molecules are biosynthesized through the cyclization of polyisoprene precursors, followed by downstream modifications with tailoring enzymes. Given their structural diversity and abundance in nature, it is no surprise that many terpenoids and their derivatives have been investigated and exploited for their therapeutic potential. The abundance of sp3-hybridized carbon atoms, in the form of methyl groups (CH3), within many of these terpenoid molecules enable them to bind biological targets with high specificity, and can also play key roles in their conformation and solubility. Despite the widespread presence and functional importance of methyl groups within these scaffolds, methods to selectively transform these groups in such structures are limited. Thus, the development of efficient strategies to further functionalize these molecules continues to be of interest and has significant implications in the development of terpenoid-based pharmaceuticals.In this issue of ACS Central Science, Hartwig and co-workers describe the site-selective functionalization of methyl groups in a range of terpenoid natural products. (2) Through a sequence of C–H silylation and oxidation, the newly installed hydroxyl group serves as a synthetic handle for subsequent substitution, elimination, or integration of the methyl carbon into the terpenoid skeleton by the cleavage of C–C bonds (Figure 1). While nature has evolved elegant strategies to functionalize C–H bonds to initiate C–C bond cleavage, synthetic methods toward this goal commonly require the preinstallation and subsequent removal of specific directing groups to control the site of functionalization, adding additional steps to a synthetic route. As outlined below, the synthetic approach described by Hartwig and co-workers overcomes this downfall by strategically utilizing the natural abundance of hydroxyl and carbonyl groups in terpenoid natural products as native directing groups for an iridium-catalyzed C(sp3)–H silylation and oxidation sequence. This hydroxymethyl moiety is then carried forward into synthetic sequences that lead to functionalization of the methyl group on a range of complex terpenoid scaffolds.Figure 1Figure 1. (a) C–H silylation and oxidation of terpenoids directed by alcohols or ketones. (b) Functionalization strategies of methyl groups in terpenoids. i. Substitution and deletion of methyl groups. ii. Elimination of methyl groups. iii. Integration of methyl groups. (c) Example terpenoid derivatives accessed through these strategies.High Resolution ImageDownload MS PowerPoint SlideThrough a sequence of C–H silylation and oxidation, the newly installed hydroxyl group serves as a synthetic handle for subsequent substitution, elimination, or integration of the methyl carbon into the terpenoid skeleton by the cleavage of C–C bonds.Building on previous work, (3) the authors have extended their efficient strategy for methyl group C–H functionalization through an iridium-catalyzed C–H silylation and oxidation sequence (Figure 1a). This reaction sequence was successfully carried out on a variety of monoterpenoids, sesquiterpenoids, triterpenoids, and steroids, producing the desired diol that would allow for subsequent functionalization of the methyl group.Following successful methyl group hydroxylation on a series of terpenoids, the authors investigated various methods for substitution, elimination, and integration of the hydroxymethyl group (Figure 1b). A formal substitution of the methyl group would allow a classically challenging late-stage diversification of the terpenoid skeleton, converting the unreactive methyl to a range of functional handles (Figure 1bi). Such substitutions were achieved by converting the newly installed primary alcohol (5) to a carboxylic acid and protecting the natural secondary alcohol as an acetate (6). The newly furnished carboxylic acid moiety then underwent substitution through various photocatalytic decarboxylations, leading to the formal substitution of the methyl group in 7 with a series of alkyl, aryl, and amine groups, as well as substitution with fluorine and deuterium. The exchange of such methyl groups for heteroaryl and amine moieties has the potential to improve binding and activity of these scaffolds, as seen in hundreds of FDA-approved drugs containing nitrogen-based heteroarenes, amino groups, or amide derivatives. (4)This work also extended substitution chemistry to the formal substitution of the methyl group with hydrogen, resulting in a methyl group deletion. This deletion is essential in the biosynthesis of cholesterol, as well as plant and fungal sterols, and is known to significantly impact the binding affinities of drugs. In this case, following the synthesis of the intermediate acid (6), decarboxylation was performed under photocatalytic conditions to afford the corresponding demethylated terpenoids (8) in high yields with complete retention of stereochemistry. This procedure elegantly avoided preinstallation of a thiohydroxamate ester, as required in a more conventional Barton decarboxylation. The authors also achieved demethylation with net inversion of stereochemistry, taking advantage of a sodium methoxide mediated retro-Claisen condensation of an intermediate aldehyde (9), leading to a loss of the methyl group as sodium formate to afford 10.Following substitution chemistry, the authors set out to excise the functionalized methyl group, while simultaneously forming an olefin through a formal elimination of methane (Figure 1bii). This newly formed alkene moiety would allow for further downstream modification of the terpenoid skeleton. This procedure followed the same sequence of oxidation to the carboxylic acid (6), followed by a photochemical decarboxyolefination protocol reported by Ritter (5) to form an alkene (see 11) in place of a gem-dimethyl unit. Notably, the authors observed complete selectivity for the terminal alkene, even in cases where the internal isomer could form.Finally, the hydroxylated methyl group could also be integrated into the ring system of the terpenoid (Figure 1biii). This allowed for a one carbon ring-expansion of the carbon skeleton, producing rare or unknown scaffolds with the potential for unique physicochemical or biological properties. Terpenoid ring expansions are typically accessed through a three-step sequence, implementing a Tiffeneau-Demjanov rearrangement that is often unselective due to the migration of either alkyl substituent, resulting in a mixture of constitutional isomers. This was overcome by implementing a Dowd-Beckwith-type ring expansion using a thionocarbonate intermediate. First, the newly installed hydroxymethyl group of 5 was selectively converted to the corresponding thionocarbonate, followed by oxidation of the remaining hydroxyl group with pyridinium chlorochromate (PCC) to afford ketone 12. Next, a well-designed interception of the primary radical formed under Barton–McCombie deoxygenation conditions allowed formation of a cyclopropane intermediate (shown) via addition to the ketone. The cyclopropane then opened to form a tertiary alkyl radical, which, following hydrogen atom abstraction, furnished the ring-expanded product 13.These three strategies of substitution, elimination, and integration allowed the authors to access a range of terpenoid derivatives (Figure 1c), with this work describing the evaluation of over 30 distinct scaffolds. This approach allows access to selectively functionalized complex terpenoid frameworks, many of which have been investigated for their therapeutic activity. Notably, the authors further proved the synthetic utility of this work by accessing glycyrrhetinic acid derivatives (see 14), some of which are drug candidates for the treatment of hyperkalemia, improving on previous syntheses in both yield and step count.This report offers a wealth of methods for selective functionalization of terpenoid methyl groups, enabling deeper exploration of their therapeutic potential and mechanisms.Overall, this report offers a wealth of methods for selective functionalization of terpenoid methyl groups, enabling deeper exploration of their therapeutic potential and mechanisms. The synthetic diversity achieved through C–H activation of the terpenoid methyl group underscores the exciting potential of this methodology to reignite the development of previously overlooked compounds, and to access previously inaccessible new-to-nature molecules with unexplored properties. Not only will this strategy have applications in the synthesis and pharmacology of terpenoid derivatives, but its broader implications will allow for the functionalization of other natural products and synthetic intermediates bearing methyl groups.Author InformationClick to copy section linkSection link copied!Corresponding AuthorLauren A. M. Murray - Department of Biochemistry, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; https://orcid.org/0000-0003-3249-0828; Email: [email protected]ReferencesClick to copy section linkSection link copied! This article references 5 other publications. 1Breitmaier, E. Terpenes: Flavors, Fragrances, Pharmaca, Pheromones; Wiley-VCH, 2006.Google ScholarThere is no corresponding record for this reference.2Kang, Y. C.; Wetterer, R. T.; Karimov, R. R.; Kojima, M.; Surke, M.; Martín-Torres, I.; Nicolai, J.; Elkin, M.; Hartwig, J. F. Substitution, Elimination, and Integration of Methyl Groups in Terpenes Initiated by C-H Bond Functionalization. ACS Cent. Sci. 2024, DOI: 10.1021/acscentsci.4c01108 Google ScholarThere is no corresponding record for this reference.3Simmons, E. M.; Hartwig, J. F. Catalytic Functionalization of Unactivated Primary C-H Bonds Directed by an Alcohol. Nature 2012, 483, 70, DOI: 10.1038/nature10785 Google Scholar3Catalytic functionalization of unactivated primary C-H bonds directed by an alcoholSimmons, Eric M.; Hartwig, John F.Nature (London, United Kingdom) (2012), 483 (7387), 70-73CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group) New synthetic methods for the catalytic functionalization of C-H bonds have the potential to revolutionize the synthesis of complex mols. However, the realization of this synthetic potential requires the ability to functionalize selectively one C-H bond in a compd. contg. many such bonds and an array of functional groups. The site-selective functionalization of aliph. C-H bonds is one of the greatest challenges that must be met for C-H bond functionalization to be used widely in complex-mol. synthesis, and processes catalyzed by transition-metals provide the opportunity to control selectivity. Current methods for catalytic, aliph. C-H bond functionalization typically rely on the presence of one inherently reactive C-H bond, or on installation and subsequent removal of directing groups that are not components of the desired mol. To overcome these limitations, we sought catalysts and reagents that would facilitate aliph. C-H bond functionalization at a single site, with chemoselectivity derived from the properties of the catalyst and site-selectivity directed by common functional groups contained in both the reactant and the desired product. Here, we show that the combination of an iridium-phenanthroline catalyst and a dihydridosilane reagent leads to the site-selective γ-functionalization of primary C-H bonds controlled by a hydroxyl group, the most common functional group in natural products. The scope of the reaction encompasses alcs. and ketones bearing many substitution patterns and auxiliary functional groups; this broad scope suggests that this methodol. will be suitable for the site-selective and diastereoselective functionalization of complex natural products. For example, treating (+)-fenchol with [Ir(cod)OMe]2 and Et2SiH gave the corresponding diethyl(hydrido)silyl ether, which was cyclized using [Ir(cod)OMe]2/Me4phen to give an intermediate oxasiloxane. The latter compd. was oxidized under Tamao-Fleming conditions and then diacylated to give hydroxyfenchol diacetate I in 66% yield. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjtFOmsLs%253D&md5=c86965f1e23fc0c06b721ada3d6c63444Vitaku, E.; Smith, D. T.; Njardarson, J. T. Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals. J. Med. Chem. 2014, 57, 10257, DOI: 10.1021/jm501100b Google Scholar4Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved PharmaceuticalsVitaku, Edon; Smith, David T.; Njardarson, Jon T.Journal of Medicinal Chemistry (2014), 57 (24), 10257-10274CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society) A review. Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Anal. of our database of U.S. FDA approved drugs reveals that 59% of unique small-mol. drugs contain a nitrogen heterocycle. In this review we report on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. The main part of our anal. is divided into seven sections: (1) three- and four-membered heterocycles, (2) five-, (3) six-, and (4) seven- and eight-membered heterocycles, as well as (5) fused, (6) bridged bicyclic, and (7) macrocyclic nitrogen heterocycles. Each section reveals the top nitrogen heterocyclic structures and their relative impact for that ring type. For the most commonly used nitrogen heterocycles, we report detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs1Wlu7%252FP&md5=7065b3b2fc6f69cede0f87479c7cf4725Sun, X.; Chen, J.; Ritter, T. Catalytic Dehydrogenative Decarboxyolefination of Carboxylic Acids. Nat. Chem. 2018, 10, 1229, DOI: 10.1038/s41557-018-0142-4 Google Scholar5Catalytic dehydrogenative decarboxyolefination of carboxylic acidsSun, Xiang; Chen, Junting; Ritter, TobiasNature Chemistry (2018), 10 (12), 1229-1233CODEN: NCAHBB; ISSN:1755-4330. (Nature Research) Alkenes are among the most versatile building blocks and are widely used for the prodn. of polymers, detergents and synthetic lubricants. Currently, alkenes are sourced from petroleum feedstocks such as naphtha. In light of the necessity to invent sustainable prodn. methods, multiple approaches to making alkenes from abundant fatty acids have been evaluated. However, all attempts so far have required at least one stoichiometric additive, which is an obstruction for applications at larger scales. Here, we report an approach to making olefins from carboxylic acids, in which every addnl. reaction constituent can be used as a catalyst. We show how abundant fatty acids can be converted to alpha-olefins, and expand the method to include structurally complex carboxylic acids, giving access to synthetically versatile intermediates. Our approach is enabled by the cooperative interplay between a cobalt catalyst, which functions as a proton redn. catalyst, and a photoredox catalyst, which mediates oxidative decarboxylation; coupling both processes enables catalytic conversion of carboxylic acids to olefins. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvV2rurnF&md5=dadc15c403fc928c694f2e3cd3ccf88cCited By Click to copy section linkSection link copied!This article has not yet been cited by other publications.Download PDFFiguresReferencesOpen PDF Get e-AlertsGet e-AlertsACS Central ScienceCite this: ACS Cent. Sci. 2024, XXXX, XXX, XXX-XXXClick to copy citationCitation copied!https://doi.org/10.1021/acscentsci.4c01569Published October 11, 2024 Publication History Published online 11 October 2024Published 2024 by American Chemical Society. This publication is licensed under CC-BY 4.0 . License Summary*You are free to share (copy and redistribute) this article in any medium or format and to adapt (remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:Creative Commons (CC): This is a Creative Commons license.Attribution (BY): Credit must be given to the creator.View full license*DisclaimerThis summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials. Article Views-Altmetric-Citations-Learn about these metrics closeArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.Recommended Articles FiguresReferencesAbstractHigh Resolution ImageDownload MS PowerPoint SlideFigure 1Figure 1. (a) C–H silylation and oxidation of terpenoids directed by alcohols or ketones. (b) Functionalization strategies of methyl groups in terpenoids. i. Substitution and deletion of methyl groups. ii. Elimination of methyl groups. iii. Integration of methyl groups. (c) Example terpenoid derivatives accessed through these strategies.High Resolution ImageDownload MS PowerPoint SlideReferences This article references 5 other publications. 1Breitmaier, E. Terpenes: Flavors, Fragrances, Pharmaca, Pheromones; Wiley-VCH, 2006.There is no corresponding record for this reference.2Kang, Y. C.; Wetterer, R. T.; Karimov, R. R.; Kojima, M.; Surke, M.; Martín-Torres, I.; Nicolai, J.; Elkin, M.; Hartwig, J. F. Substitution, Elimination, and Integration of Methyl Groups in Terpenes Initiated by C-H Bond Functionalization. ACS Cent. Sci. 2024, DOI: 10.1021/acscentsci.4c01108 There is no corresponding record for this reference.3Simmons, E. M.; Hartwig, J. F. Catalytic Functionalization of Unactivated Primary C-H Bonds Directed by an Alcohol. Nature 2012, 483, 70, DOI: 10.1038/nature10785 3Catalytic functionalization of unactivated primary C-H bonds directed by an alcoholSimmons, Eric M.; Hartwig, John F.Nature (London, United Kingdom) (2012), 483 (7387), 70-73CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group) New synthetic methods for the catalytic functionalization of C-H bonds have the potential to revolutionize the synthesis of complex mols. However, the realization of this synthetic potential requires the ability to functionalize selectively one C-H bond in a compd. contg. many such bonds and an array of functional groups. The site-selective functionalization of aliph. C-H bonds is one of the greatest challenges that must be met for C-H bond functionalization to be used widely in complex-mol. synthesis, and processes catalyzed by transition-metals provide the opportunity to control selectivity. Current methods for catalytic, aliph. C-H bond functionalization typically rely on the presence of one inherently reactive C-H bond, or on installation and subsequent removal of directing groups that are not components of the desired mol. To overcome these limitations, we sought catalysts and reagents that would facilitate aliph. C-H bond functionalization at a single site, with chemoselectivity derived from the properties of the catalyst and site-selectivity directed by common functional groups contained in both the reactant and the desired product. Here, we show that the combination of an iridium-phenanthroline catalyst and a dihydridosilane reagent leads to the site-selective γ-functionalization of primary C-H bonds controlled by a hydroxyl group, the most common functional group in natural products. The scope of the reaction encompasses alcs. and ketones bearing many substitution patterns and auxiliary functional groups; this broad scope suggests that this methodol. will be suitable for the site-selective and diastereoselective functionalization of complex natural products. For example, treating (+)-fenchol with [Ir(cod)OMe]2 and Et2SiH gave the corresponding diethyl(hydrido)silyl ether, which was cyclized using [Ir(cod)OMe]2/Me4phen to give an intermediate oxasiloxane. The latter compd. was oxidized under Tamao-Fleming conditions and then diacylated to give hydroxyfenchol diacetate I in 66% yield. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjtFOmsLs%253D&md5=c86965f1e23fc0c06b721ada3d6c63444Vitaku, E.; Smith, D. T.; Njardarson, J. T. Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals. J. Med. Chem. 2014, 57, 10257, DOI: 10.1021/jm501100b 4Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved PharmaceuticalsVitaku, Edon; Smith, David T.; Njardarson, Jon T.Journal of Medicinal Chemistry (2014), 57 (24), 10257-10274CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society) A review. Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Anal. of our database of U.S. FDA approved drugs reveals that 59% of unique small-mol. drugs contain a nitrogen heterocycle. In this review we report on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. The main part of our anal. is divided into seven sections: (1) three- and four-membered heterocycles, (2) five-, (3) six-, and (4) seven- and eight-membered heterocycles, as well as (5) fused, (6) bridged bicyclic, and (7) macrocyclic nitrogen heterocycles. Each section reveals the top nitrogen heterocyclic structures and their relative impact for that ring type. For the most commonly used nitrogen heterocycles, we report detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs1Wlu7%252FP&md5=7065b3b2fc6f69cede0f87479c7cf4725Sun, X.; Chen, J.; Ritter, T. Catalytic Dehydrogenative Decarboxyolefination of Carboxylic Acids. Nat. Chem. 2018, 10, 1229, DOI: 10.1038/s41557-018-0142-4 5Catalytic dehydrogenative decarboxyolefination of carboxylic acidsSun, Xiang; Chen, Junting; Ritter, TobiasNature Chemistry (2018), 10 (12), 1229-1233CODEN: NCAHBB; ISSN:1755-4330. (Nature Research) Alkenes are among the most versatile building blocks and are widely used for the prodn. of polymers, detergents and synthetic lubricants. Currently, alkenes are sourced from petroleum feedstocks such as naphtha. In light of the necessity to invent sustainable prodn. methods, multiple approaches to making alkenes from abundant fatty acids have been evaluated. However, all attempts so far have required at least one stoichiometric additive, which is an obstruction for applications at larger scales. Here, we report an approach to making olefins from carboxylic acids, in which every addnl. reaction constituent can be used as a catalyst. We show how abundant fatty acids can be converted to alpha-olefins, and expand the method to include structurally complex carboxylic acids, giving access to synthetically versatile intermediates. Our approach is enabled by the cooperative interplay between a cobalt catalyst, which functions as a proton redn. catalyst, and a photoredox catalyst, which mediates oxidative decarboxylation; coupling both processes enables catalytic conversion of carboxylic acids to olefins. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvV2rurnF&md5=dadc15c403fc928c694f2e3cd3ccf88c