Nucleophilic addition reactions hydrogen nucleophiles

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... 

The NOBS system undergoes an additional reaction that forms a diacyl peroxide as a result of the nucleophilic attack of the peracid anion on the NOBS precursor as shown in equation 21. This undesirable side reaction can be minimized by the use of an excess molar quantity of hydrogen peroxide (91,96) or by the use of shorter dialkyl chain acid derivatives. However, the use of these acid derivatives also appears to result in less efficient bleaching. The dependence of the acid group on the side product formation is apparentiy the result of the proximity of the newly formed peracid to unreacted NOBS in the micellar environment (91). A variety of other peracid precursor stmctures can be found (97—118). 

The order of reactivity of the hydrogen halides is HI > HBr > HCl, and reactions of simple alkenes with HCl are quite slow. The studies that have been applied to determining mechanistic details of hydrogen halide addition to alkenes have focused on the kinetics and stereochemistry of the reaction and on the effect of added nucleophiles. The kinetic studies often reveal complex rate expressions which demonstrate that more than one process contributes to the overall reaction rate. For addition of hydrogen bromide or Itydrogen... 

In contrast to the highly reactive organoboranes, borabenzene metal complexes are surprisingly inert toward nucleophiles. However, cationic complexes may undergo nucleophilic addition reactions, and nucleophilic substitution has been observed with compounds having a hydrogen or an electronegative substituent at boron. 

The nucleophilic addition of alcohols [130, 204-207], phenols [130], carboxylates [208], ammonia [130, 209], primary and secondary amines [41, 130, 205, 210, 211] and thiols [211-213] was used very early to convert several acceptor-substituted allenes 155 to products of type 158 and 159 (Scheme 7.25, Nu = OR, OAr, 02CR, NH2, NHR, NRR and SR). While the addition of alcohols, phenols and thiols is generally carried out in the presence of an auxiliary base, the reaction of allenyl ketones to give vinyl ethers of type 159 (Nu = OMe) is successful also by irradiation in pure methanol [214], Using widely varying reaction conditions, the addition of hydrogen halides (Nu= Cl, Br, I) to the allenes 155 leads to reaction products of type 158 [130, 215-220], Therefore, this transformation was also classified as a nucleophilic addition. Finally, the nucleophiles hydride (such as lithium aluminum hydride-aluminum trichloride) [211] and azide [221] could also be added to allenic esters to yield products of type 159. 

Nucleophilic substitution 313 Nucleophilic addition 337 Hydrogen-abstraction reactions 343 Carbene generation 355 Oxidation reactions 356 Reduction reactions 358 Miscellaneous reactions 360... 

By far most of the reports on addition reactions of hetero-nucleophiles to activated dienes deal with sulfur-nucleophiles17,48,80,120-137, in particular in the synthesis of 7/3-sulfur-substituted steroids which, like their carbon-substituted counterparts (Section n.A), are of interest because of their ability to inhibit the biosynthesis of estrogens80,129-137. Early investigations17,120-122 concentrated on simple acyclic Michael acceptors like methyl sorbate and 2,4-pentadienenitrile. Bravo and coworkers120 observed the formation of a 3 1 mixture of the 1,6- and 1,4-adduct in the reaction of methyl sorbate with methanethiol in basic medium (equation 39). In contrast to this, 2,4-pentadienenitrile adds various thiols regioselectively at C-5, i.e. in a 1,6-fashion (equation 40)17,121,122, and the same is true for reactions of this substrate with hydrogen sulfide (equation 41), sodium bisulfite and ethyl thioglycolate17. 

Combination of an Ri, radical with an Ra radical yields the single p-qninone methide dimer (V). Here the quinone methide cannot become stabilized by an intramolecnlar addition reaction. Instead, nucleophilic attack of its y-carbon atom occurs by a hydroxyl ion from the medium, for example aromatization and protonation of the phenoxido ion thus formed give rise to guaiacylglycerol- 3-coniferyl ether (VI), again in racemic form dc-spite its two asymmetric carbon atoms. Since attack by the extraneous hydroxyl ion can occur on either side of C-y of the p-quinone methide (V), complete equilibration of the specific hydrogens from the original conifcryl alcohol moiety in the lower half of (V) presumably occurs (sec formulae on p. 131). 

It is important to be able to look at a molecular structure and deduce the possible reactions it can undergo. Take an alkene, for example. It has a 7t bond that makes it electron-rich and able to attack electrophiles such as water, halogens and hydrogen halides in electrophilic addition reactions. Haloalkanes, on the other hand, contain polar carbon-halogen bonds because the halogen is more electronegative than carbon. This makes them susceptible to attack by nucleophiles, such as hydroxide, cyanide and alkoxide ions, in nucleophilic substitution reactions. 

The nucleophiles that are used for synthetic purposes include water, alcohols, carboxylate ions, hydroperoxides, amines, and nitriles. After the addition step is complete, the mercury is usually reductively removed by sodium borohydride. The net result is the addition of hydrogen and the nucleophile to the alkene. The regioselectivity is excellent and is in the same sense as is observed for proton-initiated additions.16 Scheme 4.1 includes examples of these reactions. Electrophilic attack by mercuric ion can affect cyclization by intramolecular capture of a nucleophilic functional group, as illustrated by entries 9-11. Inclusion of triethylboron in the reduction has been found to improve yields (entry 9).17... 

Mono-functionalization of Cyg affords, preferrably, C(l)-C(2) adducts (type a) (Figure 13.3). In some cases, for example, upon nucleophilic cyclopropanations they even represent the exclusively formed monoadducts [1-3,17]. Typical examples of addition reactions that afford monoadducts are epoxidations [18,19], osmylation [9], transition metal complex formations [20, 21], hydrogenation [13, 22], many cycloadditions [1, 2] and additions of nucleophiles [23]. For the formation and the chemical transformation of azahomo[70]fullerenes see also Chapter 12 (Schemes 12.4 and 12.5). 

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