Aryl nucleophile

A new method for the synthesis of 1,2,5-thiadiazoline 5,5-dioxides 231 was achieved by reacting activated aryl nucleophiles to the C=N double bond of the corresponding thiadiazoles 230 in the presence of AlClj as a catalyst at room temperature (00MI4). The yields of 4-aryl-derivatives ranged from 38 to 92%. 

This cycle involves, first, a monoelectronic transfer from the nickel (0) complex to the aryl halide affording a Ni(I) complex and then an oxidative addition affording a 16 electron-nickel (II) which undergoes a nucleophilic substitution of Nu-, then a monoelectronic transfer occurs once again with a second aryl halide, and, last, a reductive elimination of the arylated nucleophile regenerates the active Ni(I) species. 

According to these conclusions, it is possible to propose a catalytic cycle (Fig. 20) involving no radical species, but a copper(I) complex with the classical oxidative addition, nucleophilic substitution and reductive elimination resulting lastly in the arylated nucleophile. 

Normally, the radical anion could be the starting point for a competitive process leading also to the same arylated nucleophile but the presence of radical scavengers, such as dinitrobenzene or ditertiobutylphenol would inhibit this secondary way of arylation, increasing the overall yield of arylation. 

The asymmetric formation of industrially useful diaryl methanols can be realized through either the addition of aryl nucleophiles to aromatic aldehydes or the reduction of diaryl ketones. The latter route is frequently the more desirable, as the starting materials are often inexpensive and readily available and nonselective background reactions are not as common. For good enantioselectivity, chemical catalysts of diaryl ketone reductions require large steric or electronic differentiation between the two aryl components of the substrate and, as a result, have substantially limited applicability. In contrast, recent work has shown commercially available ketoreductase enzymes to have excellent results with a much broader range of substrates in reactions that are very easy to operate (Figure 9.6). ... 

Finally, by introducing the aryl halide into the isocyanide component, as in 96, various macrocyclic peptidomimetics containing a nonsymmetrical endo biaryl ether bridge have been synthesized [89-91]. Aryl nucleophilic substitution also takes place in this case under standard base-promoted conditions. The synthesis was also carried out on solid phase. Selected examples are shown in Fig. 19, but also a... 

In certain additions of aryl nucleophiles to C=0 double bonds, however, it is advantageous to use organolithium instead of organomagnesium compounds ... 

All)2SiCH2CH2CH2] - HSiMeCl2 various aryl nucleophiles lG-(aryl)2Me (100%) 38... 

Spontaneous decomposition of C,H5N2l IgBrj was also a source of diphenylbromonium salts 4). Diphenylbromonium and, especially, triphenyloxonium salts prov ed surprisingly stable towards electrophiles, and could be nitrated under drastic conditions to give the meta-substituted halogenonium and para-substituted oxonium cations 37). On the other hand, they arylated nucleophiles readily 38). 

H, alkyl, aryl, heteroaryl R = alkyl, aryl nucleophilic catalyst NaCN, KCN, thiazolium salts/base solvent DMF, DMSO... 

On the other hand, with aryl sulfonates (58) (R = aryl), nucleophilic substitution occurs with preferential sulfur-oxygen bond cleavage since aryl substituents show little tendency to undergo nucleophilic attack (Scheme 44). The relative order of nucleophilicity towards the sulfur atom is similar to that obtaining at a carbonyl carbon atom4b and is reported to be as shown in Figure 3. 

Transmetallation to give a Pd-C bond 180 and a B-(or Sn-) halide (shown with an aryl nucleophile and vinyl electrophile ). 

Aerobic oxidative Heck reactions also proceed between olefins and other aryl nucleophiles such as aryl tin and aryl boron reagents (Eq. (8.22)). This field started by utilizing aryl tin reagents and electron-deficient alkenes with stoichiometric base additives such as NaOAc [100], but has been significantly improved by... 

Alkynes react with acylium tetrafluoroborates in aromatic solvents to give the product corresponding to trans-addition of the acyl cation and the aryl nucleophile to the triple bond (Scheme 57). ... 

As summarized in Table 5.1, a variety of aryl nucleophiles are applicable for the catalytic arylations of alkyl halides in the presence of palladium complexes. Hence, new catalytic systems have been developed to overcome the intrinsic low propensity of alkyl halide substrates to undergo oxidative addition. As seen in this section, one solution to the problem was the unique application of bulky phosphine ligands or diene ligands, which have proven highly effective for these modem cross-couplings of alkyl haUdes. Despite such remarkable progress, however, new catalysts systems are stiU required that wiU further expand the... 

Copper complexes have been used as reagents and as catalysts for the formation of carbon-carbon bonds. The most utilized reactions mediated by copper have been couplings of alkyl halides and sulfonates because copper complexes were unique for many years as reagents that would mediate the nucleophilic substitution of alkyl and aryl nucleophiles with alkyl halides. In recent years, work has been conducted to develop copper-catalyzed versions of cross couplings with aryl halides to address the issues of the cost of palladium catalysts. Although few examples of these processes currently rival those catalyzed by palladium complexes, they do illustrate the potential of copper complexes to catalyst these types of cross-coupling processes. 

In 2011, Itami and Studer [183] developed a palladium-catalyzed C4-selective arylation of thiophenes and thiazoles with arylboronic acids. Although they had already reported the C4(/J)-selective arylation of thiophenes with aryl iodides [88] (Scheme 17.18), this C-H/C-B coupling method [using a Pd"/hipy or phen/TEMPO ((2,2,6,6-tetramethylpiperidin-l-yl)oxyl) catalyst system] enabled the use of thiazoles as aryl nucleophiles. They also applied this coupling reaction to the synthesis of the core structure of SCH-785532, which is known as a BACE inhibitor. In the same year, Itami [184] reported a direct arylation of a PAH with arylboronic acids to generate a 7t-expanded PAH. Treatment of pyrene 142 with arylboroxine 143 in the presence of Pd(OAc)2 and o-chloranil as an oxidant, followed by cydiza-tion under stoichiometric FeClj, produced PAH 144. Key to the unprecedented C-H arylation was a notable combination of Pd" and o-chloranil. 

The 1,2-cw-glycosides are prepared by a modification of the Koenigs-Knorr reaction. Reaction of the peracetylated carbohydrate with phosphorous pen-tachloride in carbon tetrachloride gives 3,4,6-tri-( -acetyl-2-0-trichloroacetyl-3-D-glucopyranosyl chloride [77] (reaction 4.57), which reacts with alkyl and aryl nucleophiles to form the a-glycopyranoside (reaction 4.62). 

The Ullmann reaction can be taken to refer to two different transformations. The first is the copper mediated coupling of two aryl groups to give a biaryl compound this is the classic Ullmann reaction. The second, the Ullmann-type reaction, is the nucleophilic aromatic substitution between aryl nucleophiles and aryl halides, the most common of which is the Ullmann ether synthesis. The classic Ullmann reaction will be reviewed in this chapter the reader is refered to several excellent reviews for details on the Ullmann-type reaction. " ... 

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