Nucleophilic additions to conjugated systems

The formation of the anions required in these reactions can be accomplished sonochemically. Bases can be used in apolar media in which they are practically insoluble. The values of the lattice energy and melting points for the usual bases are given in Table 2. 

Base KHCO3 KOH NaH NaHCOs NaOH K2CO3 Na2C03 

The addition of anions derived from malonate diester was studied recently (Fig. 7). Diethyl malonate adds to chalcone in the presence of catalytic amounts of potassium hydroxide and the rate is strongly influenced by sonication. The reaction is completed within 5 min at room temperature in toluene. Such a sensitivity suggested a sonication-induced change of mechanism, confirmed by experiments in the presence of catalytic amounts of DPPH. This radical scavenger partially inhibits the addition the existence of competitive chain electron transfer and polar mechanisms is suggested. Direct evidence is, however, missing. The additions of ethyl cyanoacetate, ethyl acetylacetate, and acetyl-acetone anions display similar characteristics, but the differences between the sonochemical and silent processes are less pronounced. 

The closely related addition of diethyl acetamidomalonate to chalcone was examined in the presence of a chiral ephedrinium salt, with the purpose of studying the effect of sonication both on the reactivity and the enantio-selectivity.47 In toluene, the yield and enantioselectivity are dramatically 

46 Bouziane, A Ratsimba, B. Berlan, J. Luche, J.L. unpublished results. 

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NUCLEOPHILIC ADDITION TO CONJUGATED SYSTEMS CONJUGATE ADDITION AND MICHAEL REACHONS... 

When a new carbon-carbon bond is produced by nucleophilic addition to conjugated systems, the process is called Michael addition. The generalised process involves an a, b-unsaturated compound and a compound containing an active hydrogen attached to a carbon atom (e.g., malonic ester, acetoacetic ester, nitrocompounds, aldehydes, ketones etc.) These are condensed in the presence of a base. The overall reaction and its mechanism can be represented as follows ... 

In the same manner as described before, arenesulfonyl thiocyanates are able to show self-addition to conjugated systems yielding sulfones243,244. More important, however, is that reactions of selenosulfonates with unsaturated systems as well as with nucleophilic carbon have been proved. 

Addition to conjugated systems can also be accomplished by any of the other three mechanisms. In each case, there is competition between 1,2 and 1,4 addition. In the case of nucleophilic or free-radical attack, the intermediates are resonance hybrids and behave like the intermediate from electrophilic attack. Dienes can give 1,4 addition by a cyclic mechanism in this way ... 

Other nucleophiles add to conjugated systems to give Michael-type products. Aniline derivatives add to conjugated aldehydes in the presence of a catalytic amount of DBU (p. 488). Amines add to conjugated esters in the presence of InCla, La(OTf)3, or YTb(OTf)3 at 3kbar, for example, to give P-amino esters. This reaction can be initiated photochemically. An intramolecular addition of an amine unit to a conjugated ketone in the presence of a palladium catalyst, or... 

The addition reactions take place at a carbon-carbon multiple bond, or carbon-hetero atom multiple bond. Because of this peculiarity, the addition reactions are not common as the first step in pyrolysis. The generation of double bonds during pyrolysis can, however, continue with addition reactions. The additions can be electrophilic, nucleophilic, involving free radicals, with a cyclic mechanism, or additions to conjugated systems such as Diels-Alder reaction. This type of reaction may explain, for example, the formation of benzene (or other aromatic hydrocarbons) following the radicalic elimination during the pyrolysis of alkanes. In these reactions, after the first step with the formation of unsaturated hydrocarbons, a Diels-Alder reaction may occur, followed by further hydrogen elimination ... 

Protonation of the enolate ion is chiefly at the oxygen, which is more negative than the carbon, but this produces the enol, which tautomerizes. So, although the net result of the reaction is addition to a carbon-carbon double bond, the mechanism is 1,4 nucleophilic addition to the C=C—C=0 (or similar) system and is thus very similar to the mechanism of addition to carbon-oxygen double and similar bonds (see Chapter 16). When Z is CN or a C=0 group, it is also possible for Y to attack at this carbon, and this reaction sometimes competes. When it happens, it is called 1,2 addition. 1,4 Addition to these substrates is also known as conjugate addition. The Y ion almost never attacks at the 3 position, since the resulting carbanion would have no resonance stabilization " ... 

In principle, pyrylium salts can be transformed to pyrans by the addiiion of an appropriate reagent to the 2-, 4-, or 6-position of the heterocycle. Although most transformations seem to be nucleophilic additions (because of the electrophilic character of the pyrylium substrates) some reactions, such as hydrogenation or one-electron reductions, are of a radical nature. Many nucleophilic additions to pyrylium salts proceeding via unstable pyran intermediates seem to be of general synthetic interest, especially in the fields of aromatic and other conjugated systems, l97 200 but are of little interest in pyran chemistry. 

Stereoelectronic effects should also play an important role in the nucleophilic 1,4-additions of anions to conjugated systems. These effects should therefore influence the Michael reaction as well as the hydrocyanation of a,6-unsaturated ketones. Studies on these reactions provided evidence that the kinetically controlled addition of a nucleophile to a cyclohexenone derivative is indeed subject to stereoelectronic effects. 

The in situ generation of an iminium ion from a carbonyl compound lowers the LUMO energy of the system. Iminium catalysis is comparable to Brpnsted- or Lewis acid activation of carbonyl compounds. The LUMO energy is lowered, the a-CH acidity increases, and nucleophilic additions including conjugate additions as well as pericyclic reactions are facilitated (Eq. 34). 

Shono and his coworkers cleverly exploited [71] the preparative possibilities of dual nucleophile/base behavior according to the relationships set out in Scheme 25. Essentially, they argued that the production of a nucleophile (M in Scheme 25) could be maintained by deprotonation of its conjugate acid, provided that the initial product of nucleophilic reaction was sufficiently basic. The way this works is illustrated in the reaction [71] in Scheme 25. Reaction is initiated by direct reduction (of CCI4) but sustained through the deprotonation of CHCI3 by the product of nucleophilic addition to furfural. Several other examples are reported [71], and the reaction type may be extended to other systems for which MX is easily reducible to M and where the acidity of MH is higher than that of the protonated addition product, MYH (Scheme 23). 

The theoretical study by Khan et al. [13] on the stereochemistry of nucleophilic addition of organometallics to unsaturated substrates can also be applied to conjugated systems. Of the three major factors affecting the orientation of the nucleophile to the substrate (see Chapter 16), the ability of the substrate to discriminate between the nucleophilic and electrophilic character of the Grignard reagent is the one most susceptible to influence by conjugation with an adjacent 7r-system. They concluded that the accessible electrophilic site (the metal) is the source of the stereochemical preference for the electron-rich olefin face. 

Problem 27.6 Draw structures of the anion expected from nucleophilic addition to each of the other positions in the conjugated system, and compare its stability with that of I. 

Nucleophilic addition to the j8-carbon is called conjugate addition or 1,4-addition, because addition occurs at the 1- and 4-positions (i.e., across the conjugated system). After 1,4-addition has occurred, the product—an enol—tautomerizes to a ketone (or to an aldehyde. Section 6.6), so the overall reaction amounts to addition to the carbon-carbon double bond, with the nucleophile adding to the j8-carbon and a proton from the reaction mixture adding to the a-carbon. Compare these reactions with the... 

The diminished electron density makes the carbon-carbon It bond less reactive toward an electrophile. However, for the same reason, the P-carbon atom is electrophilic and can react with nucleophiles. Addition reactions to conjugated systems are the subject of the next section. 

While nucleophilic additions to C=C bonds in a,P-unsaturated systems usually take place in a conjugated fashion and through mechanisms involving polar transition states, in some cases a concerted addition of the nucleophile must be considered. The addition of hydroxylamines to ethyl cinnamate is a clear example of such an unusual type of reaction. 

Scheme 4-1 SO. Sequential electrophilic and nucleophilic addition to the exocyclic conjugated double bond of a (T -triene)iron system.

As conjugated systems with alternating TT-charges, the polymethine dyes are comparatively highly reactive compounds (3). Substitution rather than addition occurs to the equalized TT-bond. If the nucleophilic and electrophilic reactions are charge-controHed, reactants can attack regiospeciftcaHy. 

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