Heteroatom-based nucleophile additions

Conjugate Addition. TBDMS triflate has been used to promote the conjugate addition of carbon- and heteroatom-based nucleophiles to a range of a./S-unsaturated carbonyl compounds, in both stoichiometric and catalytic quantities. In some cases, the silyl enol ether is isolated, in other cases, it is implied as an intermediate but hydrolyzed either in situ or by addition of an acid or a reagent known to cleave a carbon-silicon bond e.g., TBAF. Examples of carbon-based nucleophiles are shown in eqs 22-26. 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

Anionic eliminations of the following type will also be considered as belonging to the ElcB class of eliminations. Since protons on heteroatoms are usually rather acidic because of the electronegativity of the heteroatom, the first step, deprotonation, can occur with a rather weak base. The second step is beta elimination from an anion, Ep, the reverse of nucleophile addition to a polarized multiple bond. 

Coordination of a metal to the itt-orbitals of an arene opens pathways for nucleophile addition to the arene. The power of the effect is related to the oxidation state (Cr°, Mn Fe ) and peripheral ligands (Cp or CO). Under suitable conditions, both heteroatom and carbon-based nucleophiles add rapidly under mild conditions. The fate of the cyclohexadienyl intermediate depends on the conditions of the next stage of the batch-wise process. Loss of an electronegative leaving group leads to an analog of... 

Heteroatom nucleophiles were described less often. Ye and coworkers published a phospha-Michael addition catalysed by prolinol silyl ether catalyst. Another method for constructing a new C-N bond is the aza-Michael addition, that is the addition of nitrogen-based nucleophiles to a,(3-unsaturated aldehydes. Several groups published these type of reactions using diatylprolinol silyl ether as catalyst. " Fustero and coworkers used this reaction as a key step in the synthesis of biologically active chiral heterocycles. Recently, the authors showed the synthesis of quinolizidine alkaloids, such as (-l-)-myrtine, (-)-lupine and (-l-)-epiquinamide. Vicario applied 5-mercaptotetrazoles as nucleophiles towards a range of unsaturated aldehydes. The reaction proceeded via the iminium activation. The... 

Similarly amination of GO by ammonia introduces amino groups onto the G sheet that can act as basic sites on G. These basic sites can be used to promote general reactions such as aldolic condensations or nucleophilic additions (Scheme 3.30).The presence of dopant elements on the G sheet should also introduce heteroatoms with lone electron pairs that can act as Lewis base sites. In this way, N-doped or P-doped G should contain this type of basic sites and the catalytic activity of these materials should be exploited for reactions such as condensations and rearrangements. 

In principle, palladium-catalyzed alkene functionalization can be carried out by employing a series of different nucleophiles. Within the scope of the present chapter, oxygen- and nitrogen-based nucleophiles will be considered, and the discussion will be extended to metals other than palladium where appropriate for synthetic reasons. Addition of heteroatoms to alkenes in the presence of palladium catalysts can proceed through two different fundamental pathways of syn- and anti-nucleopalladation (Figure 16.1) [6]. 

It has been shown that in addition to iminium ether hydrolysis, other heteroatom and C-based nucleophiles may be incorporated into the lactam products. Through the addition of nucleophiles in a solution of DMF at ambient temperature, a range of lactams... 

Following the oxidative addition, in the transmetalation step the anionic form of the heteroatom containing coupling partner (amide, alkoxide) is transferred onto the palladium, which is usually achieved by the combined use of the neutral form of the nucleophile and a suitable base. The choice of the proper base might be crucial for the success of the coupling. The transmetalation, as depicted in Figure 2-3, usually follows a coordination-... 

The conjugate addition of heteronucleophiles to activated alkenes has been used very often in organic synthesis to prepare compounds with heteroatoms [3 to various activating functional groups, e.g. ketones, esters, nitriles, sulfones, sulfoxides and nitro groups. As in the Michael reaction, a catalytic amount of a weak base is usually used in these reactions (with amines as nucleophiles, no additional base is added). 

The nucleophilic reagent will depend on the heteroatom. If X=0 or S, base will probably be necessary, but if X=N, the amine itself should be nucleophilic enough to do conjugate addition. An example would be the amino ester 13. Numbering the carbon atoms 13a reveals the 1,3-relationship and C-N disconnection gives the secondary amine 14 and ethyl acrylate as reagents. 

The reverse reaction, i.e., the addition of water to the heterocumulene B with formation of carbonic acid derivatives A, is also known. With very few exceptions this reaction occurs spontaneously with catalysis by an acid or base. The hydration of a heterocumulene is a special example of an entire class of heterocumulene reactions, namely the addition of heteroatom nucleophiles H-Het3 (you have already come across such a reaction briefly in Section 6.1.1 in the context of the DCC activation of carboxylic acids). Occasionally, this addition... 

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