Addition Reactions of Nucleophiles to

For example, Nu can be R of R MgX or H of NaBHa- With NuH2, the adduct loses water to give —C=Nu. 

Acid increases the rate of addition of weak nucleophiles by first protonating the O of C=0, thereby enhancing the electrophilicity of the C of C=0. 

The reactivity of the carbonyl group decreases with increasing size of R s and with electron donation by R. Electron-attracting R s increase the reactivity of C=0. 

Account for this order in terms of steric and electronic factors. 

A change from a trigonal sp to a tetrahedral. v/r C in the transition state is accompanied by crowding of the four groups on C. Crowding and destabilization of the transition state is in the order 

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Otto et al. [94] have described the synthesis of spiro-(3-lactam 78 (Scheme 20) by the addition reaction of nucleophile to the exocyclic double bond of diearboxylates of 3-methylene (3-lactams 76. 

The polarisation produced by co-ordination to the metal may be transmitted through a conjugated system. Michael addition reactions of nucleophiles to TV-bonded acrylonitrile are known, and provide a convenient method for the preparation of derivatives. A wide range of nucleophiles may be used in these conjugate additions. For example, the anion of nitromethane (generated in situ) reacts with the ruthenium(m) complex [Ru(NH3)5N=CCH=CH2)]3+, 4.6, to yield a complex of 4-nitrobutyronitrile (Fig. 4-18). 

The Nicholas reaction, that is, the addition reaction of nucleophiles to cobalt-complexed propargylic cations, formed in situ, has been extensively developed. " The... 

Synthesis of nitrogen-containing heterocycles using conjugate addition reactions of nucleophiles to a,P-unsaturated imines 12H(85)993. Synthesis of quaternary a-aminophosphonic adds, including quaternary azacycloalk-2-ylphosphonates 12T6369. 

From the various conjugate addition reactions of nucleophiles to a,p-unsaturated carbonyl compounds, the use of maleimides as the Michael acceptor deserves special mention. Xue and coworkers developed a highly sustainable protocol for the Michael addition of a,a-disubstituted aldehydes to maleimides (Scheme 19.52). Remarkably, using 1 mol% of the simple bifunctional thiourea catalyst 46 and water as additive, the reaction proceeded smoothly to afford oc-branched succinimides in high yields and with... 

The nucleophilic addition reaction of urea to formaldehyde produces mainly monomethylol urea and some dimethylol urea. When the mixture is heated in presence of an acid, condensation occurs, and water is released. This is accompanied by the formation of a cross inked polymer ... 

The addition reactions of nucleophilic and electrophilic reagents to optically active a, /3-unsaturated sulfoxides have also been found to proceed in an asymmetric way. Addition of piperidine to chiral (i )-cis-propenyl p-tolyl sulfoxide 309 affords a 87 13 mixture of diastereomeric sulfoxides 310 (318). The configuration at the 3-carbon atom of the predominant diastereomer (i yS )-310 was determined by means of chemical correlation starting from optically... 

Once the oxidative-addition reaction of dioxygen to metal d -ions has occurred, the essentially electrophihc dioxygen becomes a nucleophilic peroxide ligand. Since the oxidation of substrates is associated with electron transfer from the substrate to the oxidant, i.e. in this case the dioxygen adduct, effective oxygenations require a further activation to transform the nucleophihc peroxide into an electrophihc species prior to the oxygen transfer. 

It is more difficult to conduct the addition reactions of nucleophilic radicals to electron poor alkenes because the resulting atom transfer steps are often endothermic and are too slow to propagate chains, even with iodides. An exception is illustrated in Scheme 57 resonance-stabilized vinyl radicals (especially if they are secondary or tertiary) are reactive enough to abstract iodine from alkyl iodides.178... 

The results in Table 3 were explained as shown in Scheme 4. From the fact that no kinetic isotope effect was observed in the reaction of phenyl-substituted disilenes with alcohols (Table 1), it is assumed that the addition reactions of alcohols to phenyltrimethyl-disilene proceed by an initial attack of the alcoholic oxygen on silicon (nucleophilic attack at silicon), followed by fast proton transfer via a four-membered transition state. As shown in Scheme 4, the regioselectivity is explained in terms of the four-membered intermediate, where stabilization of the incipient silyl anion by the phenyl group is the major factor favoring the formation of 26 over 27. It is well known that a silyl anion is stabilized by aryl group(s)443. Thus, the product 26 predominates over 27. However, it should be mentioned that steric effects also favor attack at the less hindered SiMe2 end of the disilene, thus leading to 26. 

Addition reaction of nucleophilic cyclohexyl radical to alkenes... 

Over the past ten years, absolute rate data have been reported on the kinetics of several bimolecular silene reactions in solution, including both head-to-tail and head-to-head dimerization the [l,2]-addition reactions of nucleophilic reagents such as water, aliphatic alcohols, alkoxysilanes, carboxylic acids and amines and the ene-addition, [2 + 2]-cycloaddition and/or [4 + 2]-cycloaddition of ketones, aldehydes, esters, alkenes, dienes and oxygen. The normal outcomes of these reactions are summarized in Scheme 1. 

Initial addition reaction of methyloxirane to 4-methyl-l-oxa-4-azaspiro[4.5]decane 164 is followed by ring expansion under thermal conditions. O-Nucleophilic attack is directed on quaternary carbon of the spiro system rather than on C-4 carbon of the oxazolidine ring, and 8,10-dimethyl-7,13-dioxa-10-azaspiro[5.7]tridecane 165 is a major product of the transformation (Scheme 42 <1995IZV1838>). 

An interesting intermolecular version of this reaction has likewise been put forward for the preparation of seven-, eight-, and nine-mem-bered carbocycle, as illustrated with a sole example in Scheme 3 [7]. In contrast to the above, these reactions begin with a carbonyl addition reaction of chloroiodoalkanes to cyclic or acyclic keto esters leading to the formation of an intermediate lactone. An intramolecular nucleophilic acyl substitution then terminates the sequence. The example in Scheme 3 represents a simple method for the construction of the 5 8 5 tricyclic ring system. 

The carbanions being electron rich behave like nucleophiles and add to the carbonyl group, for example, aldol condensation (see Chapter 3 for the addition reactions of carbanion to the carbonyl group) (Scheme 2.18). 

This review article deals primarily with addition reactions of nucleophiles, electrophiles, and neutral radicals to photochemically generated radical ions of organic compounds and some organometallic compounds. Photocyclodimerizations of electron-rich alkenes, photo-Diels-Alder reactions between alkenes and alkadienes via dimer or heterodimer radical cations, and photocycloadditions via triplexes are also included. 

The nucleophilic addition reactions of enolates to imines and related compounds (the so-called Mannich-type reactions, equation 39) are important tools in organic synthesis and a variety of electrophiles have been used to obtain the resulting nitrogen-containing... 

The Michael-type addition reaction of nucleophilic reagents with chirally modified a,jff-substituted carbonyl compounds constitutes the established methodology for the preparation of y9-substituted carbonyl compounds. The disadvantage of this type of asymmetric Michael reaction is the loading and disloading process of the chiral auxiliary on the Michael acceptor. However, this type of the reaction has been well documented to give the adduct with a high level of diastereoselectivity [83, 84]. 

During the past decade, considerable progress has been made in the area of transition metal-catalyzed cleavage and functionalization of the inert C-Cl bond in nonactivated chloroaromatic compounds. This new and important field of chemistry is reviewed in the present chapter, which describes both mechanistic and synthetic aspects of C-Cl activation. Oxidative addition reactions of chloroarenes to complexes of catalytic metals are discussed, along with their applications in a wide variety of reductive dechlorination, nucleophilic displacement, olefin arylation, coupling, and carbonylation reactions. 

In the nucleophilic addition reactions of amines to substituted aromatic aldehydes where acid catalysis is required, the use of EAN seems to be convenient. The EAN can take part in an acid-base equilibrium with the aromatic aldehydes substituted by electron-withdrawing groups. The imine products from the selected aldehydes could be obtained, confirming the dual behaviour of EAN as Brbnsted acid and potential nucleophile in these type of processes (Fig. 13.7). 

In the dimerization reaction of butadiene catalyzed by palladium complexes, nucleophiles (YH), such as amines, alcohols, phenols, carboxylic acids 41 4S>, and active methylene compounds 46) are introduced. This reaction can be explained by the attack of these nucleophiles on the jr-allylic complexes formed as intermediates-in the reactions. Takahashi, Shibano, and Hagihara confirmed by using deuterium that the hydrogen of YH migrates to C6 of the dimeric product, probably via the oxidative addition reactions of YH to the palladium species 42). 

Intramolecular nucleophilic addition reactions of enamines to suitable electrophiles placed y to the enamine nitrogen atom afford quinolizine derivatives. Examples of this strategy (Schemes 50... 

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