Nucleophilic additions by

Step 1 The acid catalyst activates the anhydride toward nucleophilic addition by protonation of the carbonyl oxygen... 

For a related study of intramolecular nucleophilic addition by an alkoxy group without generation of any new stereogenic center, see Reference 94. 

Intramolecular nucleophilic additions by nitrogen functional groups onto pendant alkynes and allenes represent an important class of type la approaches to functionalized pyrroles. A platinum-catalyzed (PtCl4) cyclization of homopropargyl azides provided an entry to 2,5-disubstituted pyrroles and 4,5,6,7-tetrahydroindoles (fused pyrroles) <06OL5349>. 

This section focuses on the preparation of fluorinated compounds through asymmetric hydrogenation/reduction reactions and nucleophilic additions by listing some examples. The first successful example of catalytic asymmetric hydrogenation of a fluoro-compound was reported by Konig et al.81... 

Nucleophilic Addition by Allylboron Derivatives. Allylboranes such as 9-allyl-9-BBN react with aldehydes and ketones to give allylic carbinols. Bond formation takes place at the y carbon of the allyl group, and the double bond shifts.33... 

General methods for the preparation of a.jS-unsaturated iron-acyl complexes are deferred to Section D 1.3.4.2.5.1.1. examples of the alkylation of enolates prepared via Michael additions to ii-0 ,/ -unsaturated complexes prepared in situ are included here. Typical reaction conditions for these one-pot processes involve the presence of an excess of alkyllithium or lithium amide which first acts as base to promote elimination of alkoxide from a /f-alkoxy complex to generate the -a,)S-unsaturated complex which then suffers 1,4-nucleophilic addition by another molecule of alkyllithium or lithium amide. The resulting enolate species is then quenched with an electrophile in the usual fashion. The following table details the use of butyllithium and lithium benzylamide for these processes44,46. 

The electron-poor aromatic ring of 1-acylpyridinium ions is known to easily undergo nucleophilic addition by carbon nucleophiles an example was proposed by Comins and coworkers, who exploited the addition of zinc enolate 68 to enantiopure 67 (R = trans-2-(a-cumyl)cyclohexyl) in a total synthesis of (-F)-cannabisativine (equation 42)125. 

Zurich, exploit the susceptibility of trifluoromethyl ketones to nucleophilic addition by amines (primary or even secondary) producing hemiaminals 104. Tertiary... 

The neutral 1,4- and 1,2-quinone methides react as Michael acceptors. However, the reactivity of these quinone methides is substantially different from that of simple Michael acceptors. The 1,6-addition of protonated nucleophiles NuH to simple Michael acceptors results in a small decrease in the stabilization of product by the two conjugated 7T-orbitals, compared to the more extended three conjugated 7T-orbitals of reactant. However, the favorable ketonization of the initial enol product (Scheme 1) confers a substantial thermodynamic driving force to nucleophile addition. By comparison, the 1,6-addition of NuH to a 1,4-quinone methide results in a large increase in the -stabilization energy due to the formation of a fully aromatic ring (Scheme 2A). This aromatic stabilization is present to a smaller extent at the reactant quinone methide, where it is represented as the contributing zwitterionic valence bond structure for the 4-0 -substituted benzyl carbocation (Scheme 1). The ketonization of the product phenol (Scheme 2B) is unfavorable by ca. 19 kcal/mol.1,2... 

In the case of TAs 39, it is impossible to determine the position of the primary nucleophilic addition by the structure of reaction products in order to define whether the 2 or 6 position is attacked, other evidence is necessary. 

Aldehydes and ketones on complete reduction give alkanes by three different methods that are complementary to each other. The Woff-Kishner reduction is done under basic conditions and is suitable for compounds that might be sensitive to acid (Following fig.). The reaction involves the nucleophilic addition by hydrazine followed by elimination of water to form a hydrazone. The mechanism is the... 

The photoinduced generation of o-quinonemethides from o-hydro-xybenzylalcohols (see Sec. 15.4.1.3) has been exploited in the intramolecular cycloaddition to a double bond for the synthesis of the hexahydrocanna-binol ring system. The reaction gives the desired product in >80% yield in acetonitrile-water, provided that the tethered alkenes are sufficiently electron-rich (trisubstituted). With less substituted derivatives nucleophilic addition by the solvent on the intermediate quinonemethide prevails over cycloaddition [300]. 

A ruthenacyclopentane 48 has been proposed as an intermediate in this reaction, after coordination of the allene and enone. Exocyclic /1-hydride elimination led to the 1,3-dienes. This ruthenacycle possessed a o-bound ruthenium allyl, allowing nucleophilic additions by alcohols or amines. Alkylative cycloetherification [29] (Eq. 20) and synthesis of pyrrolidine and piperidine [30] were thus achieved. 

Catechol oxidation catalyzed by peroxidases can be used not only for the synthesis of sulfur-substituted catechols but also for the preparation of synthetic compounds related to pheomelanins, which contain benzothiazine units. In fact, the quinone undergoes an extremely easy nucleophilic addition by thiols. For example, treating the neurotransmitter dopamine with cysteine, in the presence of HRP/H2O2, gives rise to 2-S- and 5-5-cysteinyl-catecholamine and a smaller amount of the 2-S,5-S,-di-cysteinyl-catecholamme conjugate [48, 49] (Fig. 6.3e). 

Step [2] Carry out nucleophilic addition by using CHgMgCI, followed by protonation. 

The equilibrium in this reaction favors starting material in Problem 1.14.b, the equilibrium constant for this reaction was calculated to be approximately 10 . Nonetheless, the reaction continues to a stable product because the subsequent step has a much more favorable equilibrium constant. In this next step, the carbonyl group of the aldehyde undergoes nucleophilic addition by the enolate anion to give 3-8 ... 

Vinyl sulphones (384) are subjected to nucleophilic addition by a-lithionitriles and give cyclopropanes (385) together with 3-oxothian-1,1-dioxides (386). The mechanism is given in equation 127 . It is remarkable that reaction of the sulphone with sodium... 

In the pioneering papers of Wawzonek et al. [15,186] it was demonstrated that CO2 can be added to cathodically reduced hydrocarbons to yield dihydrodicarbonylates. Examples of this kind of reaction include naphthalene [186,187], anthracene [15], 9,10-diphenylanthra-cene [15], phenanthrene [186], butadiene [187], stilbene [15], and diphenyl acetylene [187]. The mechanism is assumed to be analogous to that for protonation, with the essential steps being nucleophilic addition by an anion radical and subsequently by an anion [188]. 1,4-Addition to naphthalene suggests that carboxylation is kinetically controlled formation of dihydromonocarboxylates indicates competition with protonation. Mechanisms involving CO2 have to be considered for those hydrocarbons that are reduced at more negative potentials than [189], and for the electroinactive norbornadiene, which... 

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