Conjugate carbon nucleophiles

This review describes recent progress in asymmetric addition reactions of soft Cu (l)-conjugated carbon nucleophiles in the presence of protic functional groups, mainly focusing on chemoselectivity. Protic functimial groups of amides, hydroxy... 

The allylic esters 189 and 191 conjugated with cyclopropane undergo regio-selective reactions without opening the cyclopropane ring. The soft carbon nucleophiles are introduced at the terminal carbon to give 190, and phenylation with phenylzinc chloride takes place on the cyclopropane ring to form 192[120]. 

The l ,J -DBFOX/Ph-transition metal aqua complex catalysts should be suitable for the further applications to conjugate addition reactions of carbon nucleophiles [90-92]. What we challenged is the double activation method as a new methodology of catalyzed asymmetric reactions. Therein donor and acceptor molecules are both activated by achiral Lewis amines and chiral Lewis acids, respectively the chiral Lewis acid catalysts used in this reaction are J ,J -DBFOX/Ph-transition metal aqua complexes. 

The conjugate addition of a carbon nucleophile to an a./3-unsiituratcd acceptor is known as the Michael reaction. The best Michael reactions take place between unusually acidic donors (/3-keto esters or /3-diketones) and unhindered n,/3-unsaturated acceptors. Knamines, prepared by reaction of a ketone with a disu Instituted amine, are also good Michael donors. 

The previous sections dealt with reactions in which the new carbon-carbon bond is formed by addition of the nucleophile to a carbonyl group. Another important method for alkylation of carbon nucleophiles involves addition to an electrophilic multiple bond. The electrophilic reaction partner is typically an a,(3-unsaturated ketone, aldehyde, or ester, but other electron-withdrawing substituents such as nitro, cyano, or sulfonyl also activate carbon-carbon double and triple bonds to nucleophilic attack. The reaction is called conjugate addition or the Michael reaction. 

Scheme 2.23 provides some examples of conjugate addition reactions. Entry 1 illustrates the tendency for reaction to proceed through the more stable enolate. Entries 2 to 5 are typical examples of addition of doubly stabilized enolates to electrophilic alkenes. Entries 6 to 8 are cases of addition of nitroalkanes. Nitroalkanes are comparable in acidity to (i-ketocslcrs (see Table 1.1) and are often excellent nucleophiles for conjugate addition. Note that in Entry 8 fluoride ion is used as the base. Entry 9 is a case of adding a zinc enolate (Reformatsky reagent) to a nitroalkene. Entry 10 shows an enamine as the carbon nucleophile. All of these reactions were done under equilibrating conditions. 

The fluoride ion is an effective catalyst for conjugate additions involving relatively acidic carbon nucleophiles.292 The reactions can be done in the presence of excess... 

Cyanide ion acts as a carbon nucleophile in the conjugate addition reaction. The pK of HCN is 9.3, so addition in hydroxylic solvents is feasible. An alcoholic solution of potassium or sodium cyanide is suitable for simple compounds. 

Among the olefination reactions, those of phosphonium ylides, phosphonate anions, silylmethyl anions, and sulfone anions are discussed. This chapter also includes a section on conjugate addition of carbon nucleophiles to a, (J-unsaturated carbonyl compounds. The reactions in this chapter are among the most important and general of the carbon-carbon bond-forming reactions. 

Highly stabilized phosphorus ylides are prepared from acetylenic esters, a carbon-based nucleophile, and triphenylphosphine in aqueous media.40 In acetone-water (2 1) solvent, the reaction proceeds via the conjugate addition of triphenylphosphine to dialkyl acetylenedicarboxy-lates the resulting vinyl triphenylphosphonium salts undergo Michael addition reaction with a carbon-nucleophile to give the corresponding highly stabilized phosphorus ylides. 

The attack of carbon nucleophiles such as Grignard reagents [116, 235, 236], cuprates [183, 237-242] and C-H acidic compounds [212] on allenes 155 leads generally to the non-conjugated products 158. However, it was observed early that 158 is the product of a kinetically controlled reaction also in these cases, whereas the thermodynamically more stable product 159 is formed at longer reaction times or subse-... 

As in the case of addition reactions of carbon nucleophiles to activated dienes (Section HA), organocopper compounds are the reagents of choice for regio- and stereoselective Michael additions to acceptor-substituted enynes. Substrates bearing an acceptor-substituted triple bond besides one or more conjugated double bonds react with organocuprates under 1,4-addition exclusively (equation 51)138-140 1,6-addition reactions which would provide allenes after electrophilic capture were not observed (cf. Section IV). 

Conjugate addition of a carbon-nucleophile to an a,(3-unsaturated system. Example 1... 

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