Total Syntheses of (−)‐Acutumine and (−)‐Dechloroacutumine

King, Sandra M.; Calandra, Nicholas A.; Herzon, Seth B.

doi:10.1002/anie.201210076

Cited by 62 publications

(44 citation statements)

References 42 publications

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“…[142] The secondary chloride was installed in the final step of the synthesis via homogeneous hydrogenation of a chloroalkene precursor, dehydroacutumine ( 356 ), using a rhodium catalyst under a high pressure of hydrogen gas. The natural product was obtained as a single diastereomer, likely owing to the directing effect of the neighboring amino or hydroxyl groups through the coordination to the catalyst.…”

Section: Stereoselective Halogenation Methods and Applications In mentioning

confidence: 99%

“…Thea lkenyl halide hydrogenation approach was ak ey strategic step in the synthesis of (À)-acutumine (357, Scheme 75) by Herzon and co-workers. [142] Thes econdary chloride was installed in the final step of the synthesis via homogeneous hydrogenation of ac hloroalkene precursor, dehydroacutumine (356), using ar hodium catalyst under ah igh pressure of hydrogen gas.T he natural product was obtained as as ingle diastereomer,l ikely owing to the directing effect of the neighboring amino or hydroxy groups through the coordination to the catalyst. However,t he hydrogenation had to be stopped at low conversion because dechlorination of the product became problematic at higher conversion.…”

Section: Haloalkene Hydrogenationsmentioning

confidence: 99%

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Stereoselective Halogenation in Natural Product Synthesis

2016

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At last count, nearly 5000 halogenated natural products have been discovered. In approximately half of these compounds, the carbon atom to which the halogen is bound is sp3‐hybridized; therefore, there are an enormous number of natural products for which stereocontrolled halogenation must be a critical component of any synthesis strategy. In this Review, we critically discuss the methods and strategies used for stereoselective introduction of halogen atoms in the context of natural product synthesis. Using the successes of the past, we also attempt to identify gaps in our synthesis technology that would aid the synthesis of halogenated natural products, as well as existing methods that have not yet seen application in complex molecule synthesis. The chemistry described herein demonstrates yet again how natural products continue to provide the inspiration for critical advances in chemical synthesis.

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Section: Stereoselective Halogenation Methods and Applications In mentioning

confidence: 99%

Section: Haloalkene Hydrogenationsmentioning

confidence: 99%

Stereoselective Halogenation in Natural Product Synthesis

2016

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“…Visual disconnection of acutumine into subunits representing rings A and B led Herzon and co-workers [46] to enantioenriched cyclopentenone 62 , which is readily available from D-ribose in gram quantities, and the aromatic azide 61 as suitable starting materials (Scheme 7). Intermolecular Diels–Alder reaction between quinone 63 and trimethylsilyl cyclopentadiene 64 in the presence of the triflate salt of the Corey-Bakshi-Shibata (CBS) oxazaborolidine reagent, [47] led to endo -product 65 in excellent enantioselectivity.…”

Section: Acutuminementioning

confidence: 99%

Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms

et al. 2016

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Strategies for the total synthesis of complex natural products that contain two or more contiguous stereogenic quarternary carbon atoms in their intricate structures are reviewed with twelve representative examples. Emphasis has been put on the methods to create quarternary carbon stereocenters, including syntheses of the same natural product from different groups, thereby showcasing diversity of thought and individual creativity. A compendium of selected natural products containing two or more contiguous stereogenic quarternary carbon atoms and key reactions in their total or partial syntheses is provided in the Supporting Information section.

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“…Shortly after Shenvis publication, Herzon and co-workers reported their detailed investigation of the reduction of vinyl halides. [9] Inclined to find an alternative to the low-yielding final hydrogenation step in the total synthesis of (À)acutumine (Scheme 5, top), [10] the authors introduced a HAT hydrogenation catalyzed by [Co(acac) 2 ]. Interestingly, careful optimization revealed the beneficial effect of various additives (Cy 3 P, DTBMP, and TBHP) as well as the presence of the hydrogen donor cyclohexa-1,4-diene.…”

Section: Angewandte Highlightsmentioning

confidence: 99%

Fascinating Hydrogen Atom Transfer Chemistry of Alkenes Inspired by Problems in Total Synthesis

Simonneau

Oestreich

2015

Angew Chem Int Ed

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alkenes · hydrogen atom transfer · hydrosilanes · radicals · transition metalsReductive transformations of alkenes-hydrogenation, hydrohalogenation, and hydroboration perhaps being particularly representative examples-allow the synthetic chemist to build molecular complexity from basic chemicals. Whereas transition-metal-catalyzed hydrogenation and hydrofunctionalization reactions of alkenes have been a flourishing area of research for decades, radical-based versions have remained underestimated, probably owing to the erroneous idea that it is difficult to control radical intermediates. However, several breakthroughs were accomplished over the past couple of years, and a series of catalytic hydrogen-atom-transfertriggered transformations were developed that helped to overcome great synthetic challenges.Historically, synthetic alkene chemistry initiated by hydrogen atom transfer (HAT) began with reduction and hydration reactions that employed dihydrogen or borohydrides in combination with first-row transition-metal catalysts.[1] Shortly thereafter, in connection with the pioneering work of Mukaiyama [2] on hydrofunctionalization reactions, hydrosilanes emerged as practical and milder alternative hydride sources. Depending on the radical acceptor, several methods that employ hydrosilanes and are based on manganese, iron, and cobalt catalysts were designed to construct carbon-carbon and carbon-heteroatom bonds as well as to hydrogenate alkenes.[3] These methods share the involvement of open-shell systems as a mechanistic feature: Reversible HAT from the transition-metal hydride onto a carbon-carbon double bond generates a carbon-centered radical (Scheme 1).[4] The implementation of knowledge that was collected over three decades is now culminating in the development of new catalytic carbon-carbon bond-forming reactions as well as alkene hydrogenations and isomerizations that outcompete established methods. This remarkable progress was driven by problems arising along total syntheses of natural products.While retrosynthetically analyzing the diterpenoid rosthorin A, Baran and co-workers became interested in designing a reductive alkene coupling to construct the C4 À C5 motif of the target molecule (Scheme 2, top). After a brief examination of HAT conditions, the authors were able to cyclize a,b-unsaturated carbonyl compound 1 to cis-decalin 2 in good yield using substoichiometric amounts of cheap [Fe(acac) 3 ] and excess PhSiH 3 (Scheme 2, bottom).[5] Although the cis configuration of the ring junction in 2 was not the desired one, the efficiency and practicality of this reaction prompted the authors to investigate further intramolecular alkene couplings. Strikingly, the reaction also succeeded in more sterically demanding settings, and vicinal all-carbon quaternary centers were accessible.The Baran group also investigated an intermolecular version with various components to explore the generality of the method. For example, protected alcohols, amines, or heterocycles are tolerated in the donor alkene and acrylamides...

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Total Syntheses of (−)‐Acutumine and (−)‐Dechloroacutumine

Cited by 62 publications

References 42 publications

Stereoselective Halogenation in Natural Product Synthesis

Stereoselective Halogenation in Natural Product Synthesis

Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms

Fascinating Hydrogen Atom Transfer Chemistry of Alkenes Inspired by Problems in Total Synthesis

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