Electron deficient arylation

Nucleophilic substitutions on an aromatic ring proceed by the mechanism shown in Figure 16.17. The nucleophile first adds to the electron-deficient aryl halide, forming a resonance-stabilized negatively charged intermediate called a Meisenlieimer complex. Halide ion is then eliminated in the second step. 

Similarly, Kappe and Walla showed that (2-pyridinyl)zinc chloride can be quickly cross-coupled with electron-deficient aryl chlorides using Pd2(dba)3/ t-Bu3P.HBp4 as a precatalyst in THF at 175 °C for 10 min (Scheme 2) [21]. hi a reverse approach, 4-chloropyridine rapidly reacted with (4-methoxyphenyl) zinc chloride (Scheme 2). 

Scheme 2.14 Copper-catalysed intermolecular hydroamination of electron-deficient aryl alkenes...

A more recent publication by Weigand and Pelka has disclosed a polymer-bound Buchwald-Hartwig amination [40], Activated, electron-deficient aryl halides were coupled with conventional PS Rink resin under microwave irradiation. Subsequent acidic cleavage afforded the desired aryl amines in moderate to good yields (Scheme 7.22). Commercially available Fmoc-protected Rink amide resin was suspended in 20% piperidine/N,N-dimethylformamide at room temperature for 30 min to achieve deprotection. After washing and drying, the resin was placed in a silylated microwave vessel and suspended in dimethoxyethane (DME)/tert-butanol... 

Ketone 2 an electron-deficient aryl alkyl ketone. For the screening studies, 1 mol.% catalyst was used and the reactions were analyzed after 1 h. 

With the preformed ammonium persulphate, oxidation of sulphides to both sulphoxides and sulphones has been observed [e.g. 6, 7] whereas, when Oxone is used in conjunction with a quaternary ammonium salt, oxidation can be selectively stopped at the sulphoxide stage [6-8]. It has been recorded that electron-deficient aryl sulphides, e.g. di(4-nitrophenyl)sulphide, are not readily oxidized. 

Zimmerman and Hoffacker also observed a regioselective reaction subjecting various aryl-substituted 1,4-pentadienes to photoinduced electron transfer using DCN and DCA. The radical cations produced underwent a regioselective cyclization wherein one electron-deficient aryl group of one diarylvinyl moiety bonds to the (3-carbon of the second diarylvinyl group (Scheme 30) [41]. 

Connon and co-workers [137,147] also set out to develop a chiral catalyst which operates via an induced-fit mechanism. Derived from a 3-substituted 4-PPY and possessing a pendant aromatic group, this new catalyst (41, Fig. 7) allowed moderate to good selectivities to be achieved for a wide range of aryl alkyl i cc-alcohols. Connon [148] later showed that small improvements in selectivity could be obtained by introducing electron-deficient aryl groups. Finally, he was able to expand the substrate scope to include ec-alcohols obtained by Baylis-Hilhnan reaction [148]. 

Nagao has disclosed bifunctional chiral sulfonamide 69 as being effective for the thiolytic ASD of meso-cyclic anhydrides in up to 98% ee when employed at the 5 mol% level for 20 h at room temperature in ether [228], Catalyst 69 is a 1,2-diamine derivative in which one of the nitrogens presents as an acidic NH group (part of an electron deficient aryl sulfonamide) and the other as a nucleophihc/basic teri-amine group with the intention to act synergistically in activation of the substrate carbonyl function and thiol nucleophile respectively (Fig. 16) [228],... 

In 2008, Yamamoto et al. disclosed an asymmetric 1,3-dipolar cycloaddition of diarylnitrones 156 with ethyl vinyl ether (157) (Scheme 66). Under the influence of the bulky chiral A-triflyl phosphoramide (5)-4s (5 mol%, R = 2,6- Prj-4-Ad-C Hj), the enrfo-products 158 were formed as the major diastereomers in good yields and enantioselectivities (66 to >99%, 7 1-32 1 endolexo, 70-93% ee(endo)) [86]. High asymmetric induction was achieved only with electron-deficient aryl groups on the nitrones. 

Synthesis of 3,5-diarylisoxazoles 200 and 201 (overall yield up to 85%) by the reaction of asymmetrically substituted -diketones (199) with hydroxylamine was investigated (equation 87). It has been found that the reaction occurs with a low degree of site selectivity unless steric effects are operating. The isoxazole that has the more electron-deficient aryl group in position 3 is formed preferably when the reaction is performed with hydrox-ylamine hydrochloride. When the reaction is carried ont in a nentral medium, a reversed site stereoselectivity is observed. Similar cycUzation occurred using / -dioximes as starting material . 

The choice of an ionic liquid was shown to be critical in experiments with [NBuJBr (TBAB, m.p. 110°C) as a catalyst carrier to isolate a cyclometallated complex homogeneous catalyst, tra .s-di(ri-acetato)-bis[o-(di-o-tolylphosphino) benzyl] dipalladium (II) (Scheme 26), which was used for the Heck reaction of styrene with aryl bromides and electron-deficient aryl chlorides. The [NBu4]Br displayed excellent stability for the reaction. The recycling of 1 mol% of palladium in [NBu4]Br after the reaction of bromobenzene with styrene was achieved by distillation of the reactants and products from the solvent and catalyst in vacuo. Sodium bromide, a stoichiometric salt byproduct, was left in the solvent-catalyst system. High catalytic activity was maintained even after the formation of visible palladium black after a fourth run and after the catalyst phase had turned more viscous after the sixth run. The decomposition of the catalyst and the formation of palladium... 

The electron-deficient aryl ligands enhance the electrophilicity of the bismuth (V) center and, as a result, accelerate the first step. 

The preparations of aryl sulfides typically employ aryl halides as starting materials. The procedure described here makes use of the ubiquitous class of commercially available phenolic compounds in the form of aryl triflates, which expands the range of readily accessible aryl sulfides. Prior to this disclosure, the use of aryl triflates in a palladium-catalyzed process for the formation of aryl alkyl sulfides was unprecedented. This procedure appears to be general with regard to electronically neutral or electron-deficient aryl triflates (Table 1). The yields in Table I correspond to the initially disclosed procedure employing sodium (ert-butoxide as the base. Lower yields were obtained with the 4-nitro-... 

In 2001, Nolan described the palladium/imidazoilium salt-catalyzed coupling of aryl halides with hypervalent organostannanes.The imidazolium salt 36 in combination with Pd(OAc)2 and TBAF was found to be most effective for the cross-coupling of aryl bromides and electron-deficient aryl chlorides with aryl and vinyl stannanes. 

Mowery and DeShong used the commercially available hypervalent silicate complex TBAT as a phenylating agent for the cross-coupling reaction with allylic esters. They later reported on the use of the same organosilane for the coupling with aryl iodides and triflates and electron-deficient aryl bromides. The reactions were catalyzed by either Pd(dba)2 or [Pd(allyl)Cl]2 without the need of added phosphine ligands. 

The carbonyl ylide generated from metal carbene can also add to C=0 or C=N bonds. The [2 + 3]-cycloaddition of carbonyl ylide with G=0 bond has been used by Hodgson and co-workers in their study toward the synthesis of zaragozic acid as shown in Scheme n 27a,27d Recently, a three-component reaction approach to syn-a-hydroxy-f3-amino ester based on the trapping of the carbonyl ylide by imine has been reported.The reaction of carbonyl ylide with aldehyde or ketone generally gives l,3-dioxolanes. Hu and co-workers have reported a remarkable chemoselective Rh2(OAc)4-catalyzed reaction of phenyl diazoacetate with a mixture of electron-rich and electron-deficient aryl aldehydes. The Rh(ii) carbene intermediate reacts selectively with electron-rich aldehyde 95 to give a carbonyl ylide, which was chemospecifically trapped by the electron-deficient aldehyde 96 to afford 1,3-dioxolane in a one-pot reaction (Equation (12)). 

Many aromatic and heteroaromatic acyl silanes have been prepared by transition metal catalysed coupling (e.g. Scheme 10)23,81. This is a very successful approach for most aromatic substrates, including furyl, thienyl, pyrryl and electron-deficient aryl acyl silanes, which can otherwise be difficult to prepare. 

Iridium-catalyzed reductive coupling of acrilates and imines has been reported to provide trans (3-lactams with high diastereoselection [142], The use of electron-deficient aryl acrylates resulted in improved product yields. The mechanism, proposed by the authors, started from an in situ generated iridium hydride reacting with the acrilate to provide an iridium enolate that, then, reacted with the imine to give a (3-amido ester. Subsequent cyclization furnished the p-lactam and an iridium alcoxide. 

Backtracking from reaction product 129, speculation about the origin of this species led to the initially uncomfortable hypothesis that carbene 126 must have participated in a cycloaddition process with the tosyl unit s aryl ring in preference to C-H insertion. This curious result may be the outcome of a situation where proximity trumps electronics, as the mismatch between the electrophilic carbene and the electron deficient aryl ring would seem, a priori, to dissuade cycloaddition. 

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