Additions nucleophilic

Nucleophilic Addition.—Addition of alkyl-lithium reagents to unstrained unconjugated double bonds is observed when complexation of the alkyl-lithium is possible by an ether, thioether, or amine within the olefin. Thus (339) is converted into (340) by isopropyl-lithium in 95 % yield. A transition 

Organomagnesium halides containing a /S double bond react with olefins by addition without catalysis  

Crotylmagnesium halide reacts with ethylene almost exclusively in the form 

Reduction with sodium in diethyl ether of di-t-butyl ketone gives (344). The postulated mechanism of this interesting transformation is addition of the dianion (345) to ethylene, generated in situ from diethyl ether this was 

This category of reactions may involve nucleophilic addition either by or to the 

XPS spectra show that coordination of the RNC ligand causes a decrease of the electron density on the isocyanide carbon atom. Therefore, addition of nucleophiles to the carbon atom and addition of electrophiles to the nitrogen atom represent characteristic reactions of the isocyanide ligands. Reactions of metal isocyanide complexes with compounds of the type RXH (RX = RO, RNH, RS, etc.) lead to the formation of metal carbene complexes [Section 5.8.b, reactions (5.13)-(5.19)]. 

This reaction proceeds more readily if the isocyanide R group has electron-accepting properties and the R group has nucleophilic, electron-donating properties. 

The complexes d5-[PdX2L(CNC6H4Y-4)] (L = PPh3, AsPh3) react with amines 

s bond energies show that the carbene carbon atoms are less positive than those of the isocyanide group. Additions of amines, alcohols, and thiols afford many carbene complexes, particularly those of metals of groups 6-10. 

The reactions described in this section refer to addition of C4 of pyrazol-3-ones onto different types of electrophiles to form er-bonds. Addition to a,/f-unsaturated compounds may involve the elimination of small molecules from the electrophile. A rare case would involve a double nucleophilic reaction by the pyrazol-3-one to form a spiro compound. 

The hetero-Michael addition of 2,4-dihydropyrazol-3-one 422a-h to trichloro-acetaldimine derivatives 423a-h takes place best in apolar aprotic solvents and the 

Michael Addition of Pyrazol-3-ones to q ,/6-Unsaturated Compounds 

b in methanol containing acetic acid and obtained the 4-(2-benzofuran-l-yl)-l,2-dihydropyrazol-3-ones 464a,b. The reaction proceeds by addition of the pyrazol- 

3- one onto the ketone to give intermediate addition products 465 which condensed intramolecularly. 

So far we have looked at reactions where the attacking species on the alkene was either an electrophile, which sought out the electron rich n orbitals, or was a radical. However, it is possible for a nucleophile to attack an alkene. 

Suggest what sort of substituents on a carbon/carbon double bond would increase the likelihood of an attack by a nucleophile on such a double bond. 

The approaching nucleophile is electron rich and would naturally seek a positive centre, thus anything that reduces the ti electron density of the double bond would favour the attack by a nucleophile. Thus, groups such as cyano, nitro, or other -M groups, or even strongly -I groups such as fluorine, would favour nucleophilic attack. 

Write down the general equation for the formation of the intermediate after the attack by a nucleophile on an alkene. 

The resultant anion needs to be stabilised, and this may be done, as usual, more effectively by -M groups rather than -I groups. 

The reaction is carried out in acetonitrile, in the presence of triethyl-amine in stoichiometric quantity with the thiol compound. The introduction of triethylamine allows the thiol-thiolate balance to be changed to give the 

it is possible to use this reaction to obtain new macromolecules (di-ols or diamines) with low glass-transition temperature (Tg) and no crystalline phase. Earlier works suggested the synthesis of hydroxy-telechelic oligomers by radical addition of thiol onto dienes. But, the products obtained showed poor solubility in organic solvents and a high melting point. Our process, however, improves the properties of diol compounds (better solubility and decrease of the melting point). 

Although the imine group resembles the carbonyl group to some extent, their 

In contrast to radical-cations, radical-anions can be involved directly in radical reactions such as reductions, single bond fragmentations, cyclizations or tandem reactions. 

The reduction of halides by organotin hydrides via radical intermediates has continued to find applications since its discovery in the 1960s [43]. Another method 

Allyl acetates, halides or sulfides derived from MBH adducts can undergo 

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Example Solvation can have a profound effect on the potential energy profile for a reaction. Jorgensen s research group provided important insights into the role of solvation. Consider the nucleophilic addition of the hydroxide anion to formaldehyde ... 

These systems nitrate aromatie eompounds by a proeess of electro-philie substitution, the eharacter of whieh is now understood in some detail ( 6.1). It should be noted, however, that some of them ean eause nitration and various other reactions by less well understood processes. Among sueh nitrations that of nitration via nitrosation is especially important when the aromatic substrate is a reactive one ( 4.3). In reaetion with lithium nitrate in aeetie anhydride, or with fuming nitrie aeid, quinoline gives a small yield of 3-nitroquinoline this untypieal orientation (ef. 10.4.2 ) may be a eonsequenee of nitration following nucleophilic addition. ... 

With the dicyclohexylcarbodiimide (DCQ reagent racemization is more pronounced in polar solvents such as DMF than in CHjCl2, for example. An efficient method for reduction of racemization in coupling with DCC is to use additives such as N-hydroxysuccinimide or l-hydroxybenzotriazole. A possible explanation for this effect of nucleophilic additives is that they compete with the amino component for the acyl group to form active esters, which in turn reaa without racemization. There are some other condensation agents (e.g. 2-ethyl-7-hydroxybenz[d]isoxazolium and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline) that have been found not to lead to significant racemization. They have, however, not been widely tested in peptide synthesis. 

The Pd—C cr-bond can be prepared from simple, unoxidized alkenes and aromatic compounds by the reaction of Pd(II) compounds. The following are typical examples. The first step of the reaction of a simple alkene with Pd(ll) and a nucleophile X or Y to form 19 is called palladation. Depending on the nucleophile, it is called oxypalladation, aminopalladation, carbopalladation, etc. The subsequent elimination of b-hydrogen produces the nucleophilic substitution product 20. The displacement of Pd with another nucleophile (X) affords the nucleophilic addition product 21 (see Chapter 3, Section 2). As an example, the oxypalladation of 4-pentenol with PdXi to afford furan 22 or 23 is shown. 

Pd(II) compounds coordinate to alkenes to form rr-complexes. Roughly, a decrease in the electron density of alkenes by coordination to electrophilic Pd(II) permits attack by various nucleophiles on the coordinated alkenes. In contrast, electrophilic attack is commonly observed with uncomplexed alkenes. The attack of nucleophiles with concomitant formation of a carbon-palladium r-bond 1 is called the palladation of alkenes. This reaction is similar to the mercuration reaction. However, unlike the mercuration products, which are stable and isolable, the product 1 of the palladation is usually unstable and undergoes rapid decomposition. The palladation reaction is followed by two reactions. The elimination of H—Pd—Cl from 1 to form vinyl compounds 2 is one reaction path, resulting in nucleophilic substitution of the olefinic proton. When the displacement of the Pd in 1 with another nucleophile takes place, the nucleophilic addition of alkenes occurs to give 3. Depending on the reactants and conditions, either nucleophilic substitution of alkenes or nucleophilic addition to alkenes takes place. 

Chlorohydrin 61 is formed by the nucleophilic addition to ethylene with PdCl2 and CuCl2[103,104]. Regioselective chlorohydroxylation of the allylic amine 62 is possible by the participation of the heteroatom to give chlorohydrin 63. Allylic sulfides behave similarly[105]. 

The conversion of indoles to oxindoles can be achieved in several ways. Reaction of indoles with a halogenaling agent such as NCS, NBS or pyridin-ium bromide perbromide in hydroxylic solvents leads to oxindoles[l]. The reaction proceeds by nucleophilic addition to a 3-haloindolenium intermediate. 

Nucleophilic addition of 2-aminothiazole to the double bond of di-maleic acid hydrazine has been reported (206). No spectroscopic proof, however, is given to establish the proposed structure (60) for the resulting product (Scheme 41). 

The only reported example of nucleophilic addition to a C C bond is intramolecular it is observed when propiolic acid is added to 2-aminothiazole producing (109) (see p. 53). 

Scheme 97). Stepanov has thoroughly studied this nucleophilic reactivity some examples are given in Refs. 423 and 424. The formation of 5-benzylidene derivatives involves the same nucleophilic reactivity (422). 5-Benzothiazoline and 5-benzose enazoline derivatives of 2-diphenylaminothiazoline-4-one, have been obtained by nucleophilic addition of the thiazolone on the corresponding benzothiazolium or ben-zoselenazolium salts (433). 

The reaction of amines with the 4-phenylazo derivative (228) results in their rearrangement into triazolines. Depending on the basicity of the amines and the size of the alkoxy group, three different triazolines (229. 230, and 231) are obtained (Scheme 117) (454. 459, 472). In all cases, the first step involves nucleophilic addition of the amine to the carbonyl group followed by ring opening and further ring closure. 

Aldehydes and Ketones Nucleophilic Addition to the Carbonyl Group... 

ALDEHYDES AND KETONES NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP... 

Although the present chapter includes the usual collection of topics designed to acquaint us with a particular class of compounds its central theme is a fundamental reaction type nucleophilic addition to carbonyl groups The principles of nucleophilic addition to aide hydes and ketones developed here will be seen to have broad applicability m later chap ters when transformations of various derivatives of carboxylic acids are discussed... 

The most important chemical property of the carbonyl group is its tendency to undergo nucleophilic addition reactions of the type represented m the general equation... 

The next section explores the mechanism of nucleophilic addition to aldehydes and ketones There we 11 discuss their hydration a reaction m which water adds to the C=0 group After we use this reaction to develop some general principles we 11 then survey a number of related reactions of synthetic mechanistic or biological interest... 

PRINCIPLES OF NUCLEOPHILIC ADDITION HYDRATION OF ALDEHYDES AND KETONES... 

Principles of Nucleophilic Addition Hydration of Aldehydes and Ketones... 

Carey Organic Chemistry I 17 Aldehydes and Ketones I Text Fifth Edition Nucleophilic Addition to... 

Step 1 Nucleophilic addition of hydroxide ion to the carbonyl group ... 

Steric and electronic effects influence the rate of nucleophilic addition to a proton ated carbonyl group m much the same way as they do for the case of a neutral one and protonated aldehydes react faster than protonated ketones... 

With this as background let us now examine how the principles of nucleophilic addition apply to the characteristic reactions of aldehydes and ketones We 11 begin with the addition of hydrogen cyanide... 

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