Studies towards the enantioselective synthesis of an advanced intermediate of elisabethin A

Kaiser, Maximilian; Gärtner, Peter; Enev, Valentin S.

doi:10.1007/s00706-016-1858-8

Cited by 2 publications

(28 citation statements)

References 16 publications

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“…Our first approach was strongly guided by preliminary results. , Accordingly, target molecule 1 could be traced back to bicyclic ester 8 (Scheme ). Introduction of the C-7 methyl group was planned to be achievable by conjugate addition to the corresponding α,β-unsaturated ester.…”

Section: Resultsmentioning

confidence: 99%

“…The crude brown material was flashed over silica, and the desired product was collected as a yellow oil in 84% yield (7.56 g, 22.60 mmol). 1 H-NMR (400 MHz, CDCl 3 ): δ = 6.49 (s, 1H), 6.04 (ddd, J = 17.3, 10.3, 6.2 Hz, 2H), 5.24 (dt, J = 10.3, 1.5 Hz, 2H), 5.14 (dt, J = 17.3, 1.6 Hz, 2H), 4.75 (broad s, 1H), 4.21−4.12 (m, 1H), 3.76 (s, 3H), 2.15 (s, 3H), 0.99 (t, J = 7.9 Hz, 9H), 0.72 (q, J = 7.9 Hz, 6H); 13 Triethyl(2-methoxy-3-methyl-5-(penta-1,4-dien-3-yl)-4-((triisopropylsilyl)oxy)phenoxy)silane (18). A 500 mL Schlenk flask was charged with compound 17 (7.56 g, 22.60 mmol, 1 equiv) in 230 mL of dry THF, and the yellow mix was cooled to −85 °C.…”

Section: -M E T H O X Y -2 -M E T H Y L -6 -( P E N T a -1 4 -D I E ...mentioning

confidence: 99%

“…1 H-NMR (400 MHz, CDCl 3 ): δ = 5.85 (ddd, J = 10.4, 3.6, 1.5 Hz, 1H), 5.71 (ddd, J = 10.4, 4.3, 1.8 Hz, 1H), 3.64−3.60 (m, 4H), 3.53 (s, 3H), 3.49−3.42 (m, 1H), 2.59 (m, 1H), 2.17 (s, 3H), 1.76 (dd, J = 15.5, 11.6 Hz, 1H), 1.65 (dd, J = 15.5, 3.5 Hz, 1H), 1.36−1.24 (m, 6H), 1.20 (d, J = 6.7 Hz, 3H), 1.13−1.02 (m, 36H). 13…”

Section: Methyl (R)-3-((1s4s)-6-methoxy-47-dimethyl-58-bis-((triisopr...mentioning

confidence: 99%

“…The desired product was subjected to the next reaction without further purification. 1 H-NMR (400 MHz, CDCl 3 ): δ = 6.85 (dd, J = 11.1, 6.8 Hz, 1H), 6.51 (s, 1H), 6.03 (ddd, J = 17.2, 10.3, 7.0 Hz, 1H), 5.90 (dd, J = 11.0, 1.1 Hz, 1H), 5.30 (dt, J = 10.2, 1.1 Hz, 1H), 5.23 (dt, J = 17.2, 1.2 Hz, 1H), 4.20−4.14 (m, 1H), 3.76 (s, 3H), 2.27 (s, 3H), 1.30−1.20 (m, 3H), 1.10 (d, J = 7.0 Hz, 18H); 13 8-Methoxy-4,9-dimethyl-7-((triisopropylsilyl)oxy)-5-vinyl-4,5-dihydrobenzo[b]oxepin-2(3H)-one ((rac)-36). A 100 mL Schlenk flask was charged with CuCl (35 mg, 0.39 mmol, 5 mol %) and LiCl (30 mg, 0.68 mmol, 10 mol %), and compound (rac)-35 (2.81 g, 6.98 mmol, 1 equiv) in 46 mL of dry THF was added followed by dropwise addition of TMSCl (0.98 mL, 7.68 mmol, 1.1 equiv).…”

Section: -Methoxy-9-methyl-7-((triisopropylsilyl)oxy)-5vinylbenzo[b]o...mentioning

confidence: 99%

“…Diastereomer 38′ was collected as a pale-yellow oil in 36% yield (277 mg, 0.665 mmol). Desired 38: ), 2.59 (dd, J = 11.9, 7.1 Hz, 1H), 2.28−2.11 (m, 5H), 1.67 (dd, J = 6.6, 0.9 Hz, 3H), 1.16 (d, J = 6.6 Hz, 3H); 13 -7-(((S,E A 50 mL Schlenk flask was charged with MgBr 2 •Et 2 O (315 mg, 1.22 mmol, 1.07 equiv) and compound 38 (475 mg, 1.14 mmol, 1 equiv) in 15 mL of dry DCM. The mixture was cooled to 4 °C, and after 10 min, EtSH (0.18 mL, 2.39 mmol, 2.1 equiv) was added dropwise.…”

Section: -Hydroxy-49-dimethyl-7-((triisopropylsilyl)oxy)-5-vinyl-45-d...mentioning

confidence: 99%

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Efforts toward the Total Synthesis of Elisabethin A

et al. 2022

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We describe our efforts toward the total synthesis of the natural product elisabethin A. The first route was guided by the proposed biosynthesis, assembling the 6,6-ring system before forming the five-membered ring including the quaternary carbon. The second approach includes a high yielding cyclization under Mitsunobu conditions as a key step. It allowed the preparation of an unusual and highly functionalized bicyclic 6,5-spiro compound. Both routes share a common advanced precursor obtained from an “underdeveloped” Claisen rearrangement of an aryl dienyl ether.

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Section: Resultsmentioning

confidence: 99%

Section: -M E T H O X Y -2 -M E T H Y L -6 -( P E N T a -1 4 -D I E ...mentioning

confidence: 99%

Section: Methyl (R)-3-((1s4s)-6-methoxy-47-dimethyl-58-bis-((triisopr...mentioning

confidence: 99%

Section: -Methoxy-9-methyl-7-((triisopropylsilyl)oxy)-5vinylbenzo[b]o...mentioning

confidence: 99%

Section: -Hydroxy-49-dimethyl-7-((triisopropylsilyl)oxy)-5-vinyl-45-d...mentioning

confidence: 99%

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Efforts toward the Total Synthesis of Elisabethin A

et al. 2022

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Broadly Applicable Stereoselective Syntheses of Serrulatane, Amphilectane Diterpenes, and Their Diastereoisomeric Congeners Using Asymmetric Hydrovinylation for Absolute Stereochemical Control

et al. 2018

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A stereogenic center, placed at an exocyclic location next to a chiral carbon in a ring to which it is attached, is a ubiquitous structural motif seen in many bioactive natural products including di- and tri-terpenes and steroids. Installation of these centers has been a long-standing problem in organic chemistry. Few classes of compounds illustrate this problem better than serrulatanes and amphilectanes, which carry multiple methyl-bearing exocyclic chiral centers. Nickel-catalyzed asymmetric hydrovinylation (HV) of vinylarenes and 1,3-dienes such as 1-vinylcycloalkenes provide an exceptionally facile way of introducing these chiral centers. This manuscript documents our efforts to demonstrate the generality of the asymmetric HV to access not only the natural products, but also their various diastereoisomeric derivatives. Key to success here is the availability of highly tunable phosphoramidite Ni(II)-complexes useful for overcoming the inherent selectivity of the chiral intermediates. The yields for HV reactions are excellent, and selectivities are in the range of 92–99% for the desired isomers. Discovery of novel, configurationally fluxional, yet sterically less demanding, 2,2′-biphenol-derived phosphoramidite Ni-complexes (fully characterized by X-ray) turned out to be critical for success in several HV reactions. We also report, a less spectacular, yet equally important role of solvents in a metal-ammonia reduction for the installation of a key benzylic chiral center. Starting with simple oxygenated styrene derivatives we iteratively install the various exocyclic chiral centers present in typical serrulatane [e.g., a (+)-p-benzoquinone natural product, elisabethadione, nor-elisabethadione, helioporin D, a known advanced intermediate for the synthesis of colombiasin and elisapterosin] and amphilectane [e.g., A–F, G–J and K,L- pseudopterosins] derivatives. Our attempts to synthesize a hither-to elusive target, elisabethin A, led to a stereoselective, biomimetic route to pseudopterosin A–F aglycone.

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Studies towards the enantioselective synthesis of an advanced intermediate of elisabethin A

Cited by 2 publications

References 16 publications

Efforts toward the Total Synthesis of Elisabethin A

Efforts toward the Total Synthesis of Elisabethin A

Broadly Applicable Stereoselective Syntheses of Serrulatane, Amphilectane Diterpenes, and Their Diastereoisomeric Congeners Using Asymmetric Hydrovinylation for Absolute Stereochemical Control

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