Nucleophiles derivatives

Dienes and allylarcncs can be prepared by the Pd-catalyzcd coupling of allylic compounds with hard carbon nucleophiles derived from alkenyl and aryl compounds of main group metals. Allylic compounds with various leaving groups can be used. Some of them are unreactive with soft nucleophiles, but... 

As depicted in the following scheme, in the presence of sodium iodate and pyridine, several 5,6-dihydroxylated benzofuran derivatives were synthesized via an oxidation-Michael addition of P-dicarbonyl compounds to catechols in a one-pot procedure <06TL2615 06JHC1673>. A novel additive Pummerer reaction of 2-benzo[fc]furan sulfilimines with carbon nucleophiles derived from P-dicarbonyl compounds was also employed to the synthesis of 2,3-disubstituted benzo[b]furans <06TL595>. 

This is why SN2 type of displacements are more facile at the silicon atom than at the carbon. This is particularly so with nucleophiles derived from the more electronegative element. In compounds of the type of R3SiX (where X = leaving group), the nucleophilic displacements and hydrolysis in aqueous media occur rapidly. 

Because of partial deactivation of many catalysts by aliphatic amines, less nucleophilic derivatives such as carboxamides or carbamates are usually used as substrates for carbene N-H insertion. 

The reaction of carbon nucleophiles derived from organometallics with carboxylic acid derivatives follows closely the reactions we have already encountered in Sections 6.3.2 and 7.6.2. Organometallics... 

Chiral synthesis during the coupling reaction betw een an a-methoxy amide and a nucleophile can be achieved. One approach to this problem uses a nucleophile derived from a 2-niethyloxazoIine possessing a chiral centre, for example in the formation of the chiral amine 27 [123], A second approach uses esters of pyroglu-... 

Epoxide rings may also be opened by intramolecular nucleophiles derived from allylsilane groups (see Scheme 9) to permit aldol-like closure onto aldehyde functions. Compound 63 (Scheme 15), derived by a multistep route from L-arabinose, when activated... 

The anion of cyclopentadiene has also been demonstrated to add via ligand addition (inversion).105 385-386 Indenyl nucleophiles derived from the corresponding allylsilane have been classified as adding via ligand addition,385 but the sodium salt of the indenyl anion has curiously been suggested to add via addition directly to the metal.386... 

Type III reactions proceed by attack of a nucleophile at the central sp carbon of the allenyl system of the complexes 5. Reactions of soft carbon nucleophiles derived from active methylene compounds, such as /i-kcto esters or malonates, and oxygen nucleophiles belong to this type. The attack of the nucleophile generates the intermediates 9, which are regarded as the palladium-carbene complexes 10. The intermediates 9 pick up a proton from the active methylene compound and n-allylpalladium complexes 11 are formed, which undergo further reaction with the nucleophile, as expected, and hence the alkenes 12 are formed by the introduction of two nucleophiles. 

V. AROMATIC HALIDES A. Nucleophiles Derived from the IV Group... 

The second approach is easier practically (just mix the starting material, base, and electrophile), but works only if the base and the electrophile are compatible and don t react together. With the first approach, which is practically more demanding, the electrophile and base never meet each other, so their compatibility is not a concern. We shall start with some compounds that avoid the problem of competing aldol reactions completely, because they are not electrophilic enough to react with their own nucleophilic derivatives. 

A spectacular application allowed the synthesis of fenestranes by a three-step sequential action of cobalt nanoparticles and a palladium catalyst [131]. The cascade reaction started with a PKR of enyne 105, accomplished by the cobalt catalyst giving 106, followed by the formation of allyl-7r3 palladium complex 107 which reacted with a nucleophile derived from diethyl malonate, to give enyne 108. The final step was a second PKR that gave 109 in good yield. They used cobalt nanoparticles as with Co/charcoal the third step did not take place, apparently due to damage in this catalyst after the allylation step (Scheme 31). 

The carboxamide moiety was then examined, preparing several 2,4-dichlorophenoxy compounds in solution (9.37-9.43, Fig. 9.20). Replacement of the primary amide with small N-nucleophile-derived groups (9.41-9.43) maintained activity, as did the methyl ester-substituted 9.39 while the free acid 9.38, the deletion compiound 9.37, and more complex secondary amide analogues lost inhibitory activity. The hydroxamate function significantly increased the solubihty profile of 9.43 thus it was considered relevant for the optimization of the chemical series (Fig. 9.20). 

It was determined that carbon nucleophiles derived from carbon acids with p/fa > 22 or so are sufficiently reactive to combine with the diene ligand rapidly at —78°C to produce an anionic intermediate (Scheme 25). With a few exceptions, the regioselectivity favors formation of the homoallyl anionic complex from addition at C-2, by kinetic control. This intermediate can be quenched with protons to give the terminal alkene, or can react with excess CO to produce an acyl iron intermediate. Following the recipes of Collman s reaction, the acyl iron intermediate can lead to methyl ketones, aldehydes, or carboxylic acids. The processes are illustrated with the 1,3-cyclohexadiene complex (Scheme 25). ... 

The substitution reactions of alkyl halides by carbon nucleophiles derived from alkynes and enolate anions provide major methods for the... 

The Gabriel synthesis consists of two steps and uses a nucleophile derived from phthalimide to synthesize 1° amines via nucleophilic substitution. The Gabriel synthesis begins with... 

Gabriel synthesis (Section 25.7A) A two-step method that converts an alkyl halide into a primary amine using a nucleophile derived from phthalimide. 

Halogens (mainly chlorine) at position 4 of quinazolines 12 can be displaced by a variety of carbon nucleophiles, c.g. carbon nucleophiles derived from active methylene compounds, ketone enolates, aromatic aldehydes, organolithium reagents, alkylidenephosphorane, dimethyloxosulfonium methylide, alkynes, and cyanide. ... 

The 3f-promoted asymmetric aldol reaction of a variety of aldehydes with a silyl nucleophile derived from phenyl propionate E isomer, 98 %) resulted in moderate nnh-diastereoselectivity with relatively low enantioselectivity. With pivalaldehyde and the silyl nucleophile derived from ethyl propionate ElZ = 85 15), on the other hand, the syn isomer was obtained as a major product (22 1) with 96 % ee (Eq. 57) [43g]. 

The side product of the reaction is most likely a mixture of bromoacetoxy compounds (unspecified stereochemistry is indicated by the wavy bond lines). Electrophilic additions in nucleophilic solvents often give a mixture of products because the nucleophile derived from the electrophilic reagent (e.g., Br ) and the solvent compete for the intermediate carbocation. 

The labelling and the hints given in the problem suggest an outline biosynthesis in which two molecules of nicotinic acid, one made nucleophilic by reduction, combine to give anatabine whilst the iminium salt we made in the last problem is attacked by the same nucleophilic derivative of nicotinic acid to give anabasine. 

The first comprehensive study applying phase transfer catalysis to aromatic nucleophilic substitution appeared in 1974 and deals with carbanion nucleophiles derived from phenylalkanenitriles. The catalyst is triethylbenzylammonium chloride (TEBA).39 ... 

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