811784-15-3Relevant academic research and scientific papers
Transition-Metal-Free Suzuki-Type Cross-Coupling Reaction of Benzyl Halides and Boronic Acids via 1,2-Metalate Shift
He, Zhiqi,Song, Feifei,Sun, Huan,Huang, Yong
supporting information, p. 2693 - 2699 (2018/02/28)
Cross-coupling of organoboron compounds with electrophiles (Suzuki-Miyaura reaction) has greatly advanced C-C bond formation and has been well received in medicinal chemistry. During the past 50 years, transition metals have played a central role throughout the catalytic cycle of this important transformation. In this process, chemoselectivity among multiple carbon-halogen bonds is a common challenge. In particular, selective oxidative addition of transition metals to alkyl halides rather than aryl halides is difficult due to unfavorable transition states and bond strengths. We describe a new approach that uses a single organic sulfide catalyst to activate both C(sp3) halides and arylboronic acids via a zwitterionic boron "ate" intermediate. This "ate" species undergoes a 1,2-metalate shift to afford Suzuki coupling products using benzyl chlorides and arylboronic acids. Various diaryl methane analogues can be prepared, including those with complex and biologically active motifs. The reactions proceed under transition-metal-free conditions, and C(sp2) halides, including aryl bromides and iodides, are unaffected. The orthogonal chemoselectivity is demonstrated in the streamlined synthesis of highly functionalized diaryl methane scaffolds using multi-halogenated substrates. Preliminary mechanistic experiments suggest both the sulfonium salt and the sulfur ylide are involved in the reaction, with the formation of sulfonium salt being the slowest step in the overall catalytic cycle.
Metal-Free C-O Bond Functionalization: Catalytic Intramolecular and Intermolecular Benzylation of Arenes
Bering, Luis,Jeyakumar, Kirujan,Antonchick, Andrey P.
supporting information, p. 3911 - 3914 (2018/07/22)
A catalytic, metal-free intramolecular rearrangement of benzyl phenyl ethers using nitrosonium salt as a catalyst is described. The optimized reaction conditions enabled a catalytic and metal-free Friedel-Crafts alkylation reaction with benzylic alcohols, producing water as the stoichiometric byproduct. A comprehensive scope (>50 examples) for both approaches and application in drug synthesis were demonstrated. Mechanistic studies suggest a Lewis acid-based mechanism for the metal-free Friedel-Crafts reaction.
Unsymmetrical diarylmethanes by ferroceniumboronic acid catalyzed direct friedel-crafts reactions with deactivated benzylic alcohols: Enhanced reactivity due to ion-pairing effects
Mo, Xiaobin,Yakiwchuk, Joshua,Dansereau, Julien,Adam McCubbin,Hall, Dennis G.
supporting information, p. 9694 - 9703 (2015/08/18)
The development of general and more atom-economical catalytic processes for Friedel-Crafts alkylations of unactivated arenes is an important objective of interest for the production of pharmaceuticals and commodity chemicals. Ferroceniumboronic acid hexafluoroantimonate salt (1) was identified as a superior air- and moisture-tolerant catalyst for direct Friedel-Crafts alkylations of a variety of slightly activated and neutral arenes with stable and readily available primary and secondary benzylic alcohols. Compared to the use of classical metal-catalyzed alkylations with toxic benzylic halides, this methodology employs exceptionally mild conditions to provide a wide variety of unsymmetrical diarylmethanes and other 1,1-diarylalkane products in high yield with good to high regioselectivity. The optimal method, using the bench-stable ferroceniumboronic acid salt 1 in hexafluoroisopropanol as cosolvent, displays a broader scope compared to previously reported catalysts for similar Friedel-Crafts reactions of benzylic alcohols, including other boronic acids such as 2,3,4,5-tetrafluorophenylboronic acid. The efficacy of the new boronic acid catalyst was confirmed by its ability to activate primary benzylic alcohols functionalized with destabilizing electron-withdrawing groups like halides, carboxyesters, and nitro substituents. Arene benzylation was demonstrated on a gram scale at up to 1 M concentration with catalyst recovery. Mechanistic studies point toward the importance of the ionic nature of the catalyst and suggest that factors other than the Lewis acidity (pKa) of the boronic acid are at play. A SN1 mechanism is proposed where ion exchange within the initial boronate anion affords a more reactive carbocation paired with the non-nucleophilic hexafluoroantimonate counteranion.
Transition metal-free domino sequential synthesis of (E)-stilbenes, biaryl methanes and biaryl ethers using Et2AlCl as a Lewis acid
Sarkar, Satinath,Jana, Manoranjan,Tadigoppula, Narender
, p. 18755 - 18758 (2013/10/22)
A transition metal-free domino process has been developed, for the first time, to synthesize (E)-stilbenes, biaryl methanes and biaryl ethers from substituted α,β-unsaturated ketones, benzyl acetones and phenacyl ethers, respectively, in moderate to good yields at room temperature using diethyl aluminium chloride (Et2AlCl) as a Lewis acid. The Royal Society of Chemistry 2013.
Electrophilic alkylations in neutral aqueous or alcoholic solutions
Hofmann, Matthias,Hampel, Nathalie,Kanzian, Tanja,Mayr, Herbert
, p. 5402 - 5405 (2007/10/03)
Acid-free Friedel-Crafts chemistry: A paradox? Nucleophilicity scales, based on reactions with benzhydrylium ions, show that many π systems are more nucleophilic than aqueous or alcoholic solutions that are generally employed as solvents for SN1 reactions. Solvolytically generated carbocations can, therefore, be trapped by donor-substituted arenes and alkenes to form products of Friedel-Crafts-type reactions in neutral aqueous solutions (see scheme).
