Nicholas Reactions of Alkynyl- and Alkenyltrifluoroborates

Onge, Brent St; Green, James R.

doi:10.1055/s-0036-1588528

Cited by 10 publications

(5 citation statements)

References 5 publications

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“…We were very disappointed when we found that both BT8O and IC8O are extremely unstable and could not be isolated after decomplexation using a dozen common Co deprotecting reagents. In all cases of using either oxidizing decomplexation ( N -methylmorpholine- N -oxide (NMO), I 2 , cerium ammonium nitrate (CAN)) ,, or ligand exchangeable reagent: tetrabutylammonium fluoride (TBAF), ,, only complex polymeric mixtures were obtained. By treatment with other ligand exchangeable reagents (ethan-1,2-diamine (EDA), dimethylacetylenedicarboxylate (DMAD)), the reaction did not take place at all (Table S1).…”

Section: Resuts and Discussionmentioning

confidence: 99%

Heterocycloalkynes Fused to a Heterocyclic Core: Searching for an Island with Optimal Stability-Reactivity Balance

et al. 2021

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In the search for fundamentally new, active, stable, and readily synthetically accessible cycloalkynes as strain-promoted azide–alkyne cycloaddition (SPAAC) reagents for bioorthogonal bioconjugation, we integrated two common approaches: the reagent destabilization by the increase of a ring strain and the transition state stabilization through electronic effects. As a result new SPAAC reagents, heterocyclononynes fused to a heterocyclic core, were created. These compounds can be obtained through a general synthetic route based on four crucial steps: the electrophile-promoted cyclization, Sonogashira coupling, Nicholas reaction, and final deprotection of Co-complexes of cycloalkynes from cobalt. Varying the natures of the heterocycle and heteroatom allows for reaching the optimal stability-reactivity balance for new strained systems. Computational and experimental studies revealed similar SPAAC reactivities for stable 9-membered isocoumarin- and benzothiophene-fused heterocycloalkynes and their unstable 8-membered homologues. We discovered that close reactivity is a result of the interplay of two electronic effects, which stabilize SPAAC transition states (πin* → σ* and π* → πin*) with structural effects such as conformational changes from eclipsed to staggered conformations in the cycloalkyne scaffold, that noticeably impact alkyne bending and reactivity. The concerted influence of a heterocycle and a heteroatom on the polarization of a triple bond in highly strained cycles along with a low HOMO–LUMO gap was assumed to be the reason for the unpredictable kinetic instability of all the cyclooctynes and the benzothiophene-fused oxacyclononyne. The applicability of stable isocoumarin-fused azacyclononyne IC9N-BDP-FL for in vitro bioconjugation was exemplified by labeling and visualization of HEK293 cells carrying azido-DNA and azido-glycans.

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Section: Resuts and Discussionmentioning

confidence: 99%

Heterocycloalkynes Fused to a Heterocyclic Core: Searching for an Island with Optimal Stability-Reactivity Balance

et al. 2021

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“…The expected products, 1,4-(skipped) diynes and enynes, are valuable both as synthetic intermediates and for their presence as extant motifs in natural products . In 2017, we communicated a preliminary report on their reactivity, and we now wish to provide a more detailed description of the experimental reactivity patterns of alkynyl- and alkenyltrifluoroborates with propargyldicobalt cations, supported by a density functional theory (DFT)-based computational evaluation of the most likely reaction pathways.…”

Section: Introductionmentioning

confidence: 84%

Reaction of Alkynyl- and Alkenyltrifluoroborates with Propargyldicobalt Cations: Alkynylation, Alkenylation, and Cyclopropanation Product Pathways

et al. 2021

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The Lewis acid-mediated Nicholas reactions of propargyl acetate–Co2(CO)6 complexes with a series of potassium alkynyltrifluoroborates and potassium alkenyltrifluoroborates are described. Alkynyltrifluoroborates directly alkynylate the intermediate propargyldicobalt cations. In contrast, alkenyltrifluoroborates proceed through one of the three modes of dominant reactivity: C-2-substituted alkenyltrifluorobrates directly alkenylate, predominantly with the retention of stereochemistry. C-1-substituted alkenyltrifluoroborates alkenylate at C-2. Potassium vinyltrifluoroborate incorporates a cyclopropane at the site propargyl to alkynedicobalt. Computational analysis of these systems explains the differential modes of reactivity of alkenyltrifluoroborates and outlines the probable mechanisms for the formation of each product.

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“…We have reported recently that both potassium vinyltrifluoroborates and alkynyltrifluoroborates engage successfully in Nicholas reactions, 15 and so we attempted representative examples here. Potassium ( E )-trifluoro(4-methylstyryl)borate engaged in reaction with 6a to give 7p (56%), while potassium trifluoro(1-hexynyl)borate afforded 7q in 78% yield.…”

Section: Table 1 Optimization Of the Allylation Of ...mentioning

confidence: 99%

Nicholas Reactions of Pentadiynyl–Co2(CO)6 Cations. Synthesis of Antimalarial Hinokiresinol Analogues

Green,

Muresan

2024

Synthesis

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Penta-1,4-diyn-3-ol Co2(CO)6 complexes undergo Lewis acid mediated Nicholas reactions with high selectivity at the C-3 site, to give skipped (1,4-) diyne complexes. The compatible nucleophiles have a wide range of reactivity. The methodology has been applied to the synthesis of both (E)- and (Z)- isomers of an hinokiresinol and nyasol analogue, the (E)- isomer of which is known to have elevated antiplasmodial and antimalarial activity.

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Nicholas Reactions of Alkynyl- and Alkenyltrifluoroborates

Cited by 10 publications

References 5 publications

Heterocycloalkynes Fused to a Heterocyclic Core: Searching for an Island with Optimal Stability-Reactivity Balance

Heterocycloalkynes Fused to a Heterocyclic Core: Searching for an Island with Optimal Stability-Reactivity Balance

Reaction of Alkynyl- and Alkenyltrifluoroborates with Propargyldicobalt Cations: Alkynylation, Alkenylation, and Cyclopropanation Product Pathways

Nicholas Reactions of Pentadiynyl–Co2(CO)6 Cations. Synthesis of Antimalarial Hinokiresinol Analogues

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