Generation of α- acylcarbenium ions : a novel uncatalysed c-c bond formation at room temperature

Kulkarni, Gururaj C.; Karmarkar, Sanjay N.; Kelkar, Shriniwas L.; Murzban, Wadia S.

doi:10.1016/s0040-4020(01)86025-7

Cited by 12 publications

(5 citation statements)

References 10 publications

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“…The intermediately formed carbenium ions [ 111] are often used for the synthesis of benzofuran derivatives, as illustrated for example by the production of 2,3-diphenylbenzofuran by the condensation of 4-methoxyphenyl 4-methoxyphenylchioromethyl ketone with 4-methoxyphenoi [112]. The controlling stage of the process is the formation of the c~-acylcarbenium ion as a result of the elimination of a chlorine atom.…”

Section: XXXVIImentioning

confidence: 99%

Methods for the synthesis of benzofuran derivatives (review)

Кадиева¹,

Oganesyan²

1997

Chem Heterocycl Compd

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Section: XXXVIImentioning

confidence: 99%

Methods for the synthesis of benzofuran derivatives (review)

Кадиева¹,

Oganesyan²

1997

Chem Heterocycl Compd

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“…α-Acylcarbenium ions have been trapped in solution by treating α-halobenzyl ketones with AgSbF 6 in the presence of phenol and methanol 13,14…”

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confidence: 99%

“…Such a method would provide a simple route to α,α-diaryl ketones. α-Acylcarbenium ions have been trapped in solution by treating α-halobenzyl ketones with AgSbF 6 in the presence of phenol and methanol. , …”

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confidence: 99%

Lewis Acid-Promoted Friedel−Crafts Alkylation Reactions with α-Ketophosphate Electrophiles

Smith

Johnson

2010

Org. Lett.

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The BF 3 ·OEt 2 -promoted nucleophilic substitution of α-aryl-α-ketophosphates to afford α,α-diaryl ketone products is described. Electron-rich α-ketophosphates perform best, with electron-neutral and electron-poor substrates also tolerated. The reaction is tolerant of a range of aromatic, heteroaromatic and non-aromatic nucleophiles, with yields ranging from 44-84%. Enantioenriched starting material yields racemic product, suggesting an S N 1 pathway via an acylcarbenium ion.α-Aryl carbonyl compounds have garnered considerable attention as synthetic targets, most notably in the chemical production of non-steroidal anti-inflammatory drugs (NSAIDs). Common drugs such as naproxen, ibuprofen, fluribiprofen, and dichlofenac all contain this moiety. 1 The Pd(0)-catalyzed α-arylation of ketones, pioneered concurrently by Buchwald, Hartwig and Miura in 1997, has served as the premier route to these products.2 , 3 In recent years, this methodology has been expanded to include esters, amides, aldehydes, and lactones as carbonyl coupling partners in the presence of an aryl halide or triflate and a Bronsted base. , 5The aforementioned transition metal-catalyzed routes take advantage of the conventional reactivity patterns of nucleophilic ketone enolates and electrophilic Pd(II) intermediates to arrive at α-arylated carbonyls. We wanted to observe whether formation of an Ar-C α bond was possible through polarity reversal, or umpolung methodology 6 , with Friedel-Crafts alkylation occuring at an electrophilic α-carbon (Figure 1). Such a route could be envisioned from a substrate with a sufficient nucleofuge in place adjacent to the carbonyl functionality ( Figure 2).An umpolung α-alkylation route has precedent. In 2004, Ready and Malosh described the copper-catalyzed cross-coupling of primary and secondary organozinc halides with α-chloroketones, providing α-branched ketones in high yields with inversion of configuration at the α-carbon. 7 In 2008, Breit and Studte described a zinc-catalyzed stereospecific sp 3 -sp 3 crosscoupling reaction involving alkyl Grignard reagents and α-hydroxy ester triflates. 8 The umpolung alkylation route becomes especially attractive if the needed functionality (i.e. jsj@unc.edu . Supporting Information Available: Experimental procedures, spectroscopic and analytical data for all new compounds. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript nucleofuge) can be directly installed in conjunction with another synthetic operation. In this context, we noted a potential connection to our previous work demonstrating that cyanidecatalyzed additions of acyl phosphonates to aldehydes provide α-keto phosphate products (Figure 2). 9,10 Acyl phosphonates are easily prepared in one step via the Michaelis-Arbuzov reaction, rendering them a convenient acyl donor. The "phospha-benzoin" reaction forms a C-C bond and installs a potential nucleofuge in a concomitant fashion. In p...

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“…Finally, cyclodehydration of the resulting 2-arylated aryloxyketones was attempted (Scheme ) . Several different reaction conditions were screened for cyclization.…”

Section: Resultsmentioning

confidence: 99%