Gram-Scale Synthesis of the Co(nmp)2 Catalyst to Prepare trans-2,5-Disubstituted Tetrahydrofurans by the Aerobic Oxidative Cyclization of Pent-4-en-1-ols

Morra, Barbora; Morra, Nicholas A.; MacDonald, Daniel G.; Pagenkopf, Brian L.

doi:10.1055/s-0039-1690730

Cited by 7 publications

(5 citation statements)

References 15 publications

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“…As expected, this di-unsaturated compound underwent a highly selective cobalt-catalyzed oxidative etherificaton to furnish the desired trans -configured THF derivative 11 in 72% yield as the only isomer; to this end, cobalt complex 21 proved optimal. , Subsequent oxidation of the newly formed primary alcohol to the corresponding acid was followed by elaboration into enone 13 by the addition of 2-methyl-1-propenylmagnesium bromide to Weinreb amide 12 . Somewhat unexpectedly, the crude material contained variable amounts of ketone with the double bond out of conjugation; exposure to catalytic DBU rectified the outcome and gave the desired product in almost quantitative yield.…”

Section: Resultsmentioning

confidence: 63%

Total Syntheses of Nominal and Actual Prorocentin

et al. 2023

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The dinoflagellate-derived polyether prorocentin is a co-metabolite of the archetypical serine/threonine phosphatase inhibitor okadaic acid. Whereas a structural relationship cannot be missed and a biosynthetic link was proposed, it is currently unknown whether there is any parallel in the bioactivity profile of these natural products. However, it was insinuated in the past that the structure assigned to prorocentin might need to be revised. Indeed, re-examination of the published spectra cast doubts as to the constitution of the fused/spirotricyclic BCD-ring system in the core. To clarify this issue, a flexible synthesis blueprint was devised that allowed us to obtain the originally proposed structure as well as the most plausible amended structure. The key to success was late-stage gold-catalyzed spirocyclization reactions that furnished the isomeric central segments with excellent selectivity. The lexicon of catalytic transformations used to make the required cyclization precursors comprised a titanium-mediated ester methylenation/metathesis cascade, a rare example of a gold-catalyzed allylic substitution, and chain extensions via organocatalytic asymmetric aldehyde propargylation. A wing sector to be attached to the isomeric cores was obtained by Krische allylation, followed by a superbly selective cobalt-catalyzed oxidative cyclization of the resulting di-unsaturated alcohol with the formation of a 2,5-trans-disubstituted tetrahydrofuran; the remaining terminal alkene was elaborated into an appropriate handle for fragment coupling by platinum-catalyzed asymmetric diboration/oxidation. The assembly of the different building blocks to the envisaged isomeric target compounds proved that the structure of prorocentin needs to be revised as disclosed herein.

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Section: Resultsmentioning

confidence: 63%

Total Syntheses of Nominal and Actual Prorocentin

et al. 2023

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“…The required aldehyde 18 was attained in either enantiomeric form starting from 16 by a cobalt‐catalyzed oxidative cyclization which forms the trans ‐disubstituted tetrahydrofuran ring with excellent selectivity (Scheme 3). [45] This exact transformation had already served our previous total synthesis of amphidinolide C and F; [46] it illustrates the chemoselectivity of such oxidative Mukaiyama cyclization reactions in that only the olefinic site of 16 is engaged by the cobalt catalyst, [45, 47] whereas the triple bond remains untouched [13a,b, 46] …”

Section: Methodsmentioning

confidence: 82%

The Formosalides: Structure Determination by Total Synthesis

et al. 2020

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Total synthesis allowed the constitution of the cytotoxic marine macrolides of the formosalide family to be confirmed and their previously unknown stereostructure to be assigned with confidence.T he underlying blueprint was inherently modular to ensure that each conceivable isomer could be reached. This flexibility derived from the use of strictly catalyst controlled transformations to set the stereocenters,e xcept for the anomeric position, whichi su nder thermodynamic control;a sa ne xtra safety measure,a ll stereogenic centers were set prior to ring closure to preclude any interference of the conformation adopted by the macrolactone rings of the different diastereomers.Late-stage macrocyclization by ring-closing alkyne metathesis was followed by ap latinum-catalyzed transannular 6-exo-dig hydroalkoxylation/ketalization to craft the polycyclic frame.T he side chain featuring avery labile unsaturation pattern was finally attached to the core by Stille coupling.

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“…17 ) to give iodide 12 (82%), which was reacted with (vinyl) 2 Cu(CN)Li 2 to deliver γ-hydroxy olefin 8 (92%, Scheme 2A ). Mukaiyama cyclization of 8 ( Co-I (10 mol%), 18 t -BuOOH (10 mol%), i-PrOH, 60 °C under O 2 ) afforded 2,5- trans -tetrahydrofuran 13 in 68% yield with greater than 20 : 1 diastereoselectivity. The relative configuration of 13 was confirmed by an NOE experiment as shown.…”

Section: Resultsmentioning

confidence: 99%