Dual Brønsted/Lewis acid catalysis involving environmentally benign, readily accessible protic acid and iron promotes site-selective tert -butylation of electron-rich arenes using di- tert -butylperoxide. This transformation inspired the development of a synergistic Brønsted/Lewis acid catalyzed aromatic alkylation that fills a gap in the Friedel–Crafts reaction literature by employing unactivated tertiary alcohols as alkylating agents, leading to new quaternary carbon centers. Corroborated by DFT calculations, the Lewis acid serves a role in enhancing the acidity of the Brønsted acid. The use of non-allylic, non-benzylic, and non-propargylic tertiary alcohols represents an underexplored area in Friedel–Crafts reactivity.
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This content will become publicly available on December 1, 2024
The double protonation of dihapto-coordinated benzene complexes enables dearomatization using aromatic nucleophiles
Abstract Friedel-Crafts Arylation (the Scholl reaction) is the coupling of two aromatic rings with the aid of a strong Lewis or Brønsted acid. This historically significant C–C bond forming reaction normally leads to aromatic products, often as oligomeric mixtures, dictated by the large stabilization gained upon their rearomatization. The coordination of benzene by a tungsten complex disrupts the natural course of this reaction sequence, allowing for Friedel-Crafts Arylation without rearomatization or oligomerization. Subsequent addition of a nucleophile to the coupled intermediate leads to functionalized cyclohexenes. In this work, we show that by coordinating benzene to tungsten through two carbons (dihapto-coordinate), a rarely observed double protonation of the bound benzene is enabled, allowing its subsequent coupling to a second arene without the need of a precious metal or Lewis acid catalyst.
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- Award ID(s):
- 2018870
- NSF-PAR ID:
- 10459024
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 14
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract The direct Friedel–Crafts‐type coupling and dedinitrogenation reactions of vinyldiazo compounds with aromatic compounds using a metal‐free strategy are described. This Brønsted acid catalyzed method is efficient for the formation of α‐diazo β‐carbocations (vinyldiazonium ions), vinyl carbocations, and allylic or homoallylic carbocation species via vinyldiazo compounds. By choosing suitable nucleophilic reagents to selectively capture these intermediates, both trisubstituted α,β‐unsaturated esters, β‐indole‐substituted diazo esters, and dienes are obtained with good to high yields and selectivity. Experimental insights implicate a reaction mechanism involving the selective protonation of vinyldiazo compounds and the subsequent release of dinitrogen to form vinyl cations that undergo intramolecular 1,3‐ and 1,4‐ hydride transfer processes as well as fragmentation.
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Abstract The direct Friedel–Crafts‐type coupling and dedinitrogenation reactions of vinyldiazo compounds with aromatic compounds using a metal‐free strategy are described. This Brønsted acid catalyzed method is efficient for the formation of α‐diazo β‐carbocations (vinyldiazonium ions), vinyl carbocations, and allylic or homoallylic carbocation species via vinyldiazo compounds. By choosing suitable nucleophilic reagents to selectively capture these intermediates, both trisubstituted α,β‐unsaturated esters, β‐indole‐substituted diazo esters, and dienes are obtained with good to high yields and selectivity. Experimental insights implicate a reaction mechanism involving the selective protonation of vinyldiazo compounds and the subsequent release of dinitrogen to form vinyl cations that undergo intramolecular 1,3‐ and 1,4‐ hydride transfer processes as well as fragmentation.
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Deoxypodophyllotoxin contains a core of four fused rings (A to D) with three consecutive chiral centers, the last being created by the attachment of a peripheral trimethoxyphenyl ring (E) to ring C. Previous studies have suggested that the iron(II)- and 2-oxoglutarate–dependent (Fe/2OG) oxygenase, deoxypodophyllotoxin synthase (DPS), catalyzes the oxidative coupling of ring B and ring E to form ring C and complete the tetracyclic core. Despite recent efforts to deploy DPS in the preparation of deoxypodophyllotoxin analogs, the mechanism underlying the regio- and stereoselectivity of this cyclization event has not been elucidated. Herein, we report 1) two structures of DPS in complex with 2OG and (±)-yatein, 2) in vitro analysis of enzymatic reactivity with substrate analogs, and 3) model reactions addressing DPS’s catalytic mechanism. The results disfavor a prior proposal of on-pathway benzylic hydroxylation. Rather, the DPS-catalyzed cyclization likely proceeds by hydrogen atom abstraction from C7', oxidation of the benzylic radical to a carbocation, Friedel–Crafts-like ring closure, and rearomatization of ring B by C6 deprotonation. This mechanism adds to the known pathways for transformation of the carbon-centered radical in Fe/2OG enzymes and suggests what types of substrate modification are likely tolerable in DPS-catalyzed production of deoxypodophyllotoxin analogs.more » « less
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Abstract The syntheses of the 2,9‐dimesityl‐1,10‐phenanthroline (
dmesp ) metal complexes, [Cu(dmesp)(MeCN)]PF6(1 ), [Cu(dmesp)2]PF6(2 ), Fe(dmesp)Cl2(3 ), Co(dmesp)Cl2(4 ), Ni(dmesp)Cl2(5 ), Zn(dmesp)Cl2(6 ), Pd(dmesp)MeCl (7 ), Cu(dmesp)Cl (8 ), and Pd(dmesp)2Cl2(9 ), in good to high yields are described. These complexes were characterized by1H and13C NMR spectroscopy, HR–MS (ESI and/or APPI), and elemental analysis (CHN). The solid‐state structures of complexes1 –8 were determined by single‐crystal X‐ray analysis and their photophysical properties were also characterized. To demonstrate the versatility of this new platform, complexes3 –5 ,8 , and9 were employed in the catalytic oligomerization of ethylene using modified methyl aluminoxane (MMAO) as the cocatalyst, where Co(II) and Ni(II) complexes (4 and5 , respectively) were found to exhibit moderate selectivity for catalytic dimerization of ethylene to butenes over tri‐ or tetramerization. Complex8 is an effective catalyst of both the commonly encountered “click” reaction and amine arylation chemistries. Complexes6 and9 were found to be excellent catalysts for Friedel‐Crafts alkylation and Suzuki‐Miyaura coupling, respectively.
