Nucleophilic addition reactions with carbon nucleophiles

In contrast, the reaction of an aldehyde or a ketone with a carbon or hydrogen nucleophile forms a stable tetrahedral compound because the newly formed sp carbon is not bonded to a second electronegative atom. Thus, aldehydes and ketones undergo nucleophilic addition reactions with carbon and hydrogen nucleophiles, whereas they undergo nucleophilic addition-elimination reactions with nitrogen nucleophiles. 

The use of carbon nucleophiles in Michael-type addition reactions with pteridine and its derivatives leads to a quite complicated and divergent pattern. These reactions are strongly dependent on the nature of the carbon nucleophile and can be divided into various categories. 

It has long been known that a, / -unsaturated sulfones resemble a, /i-unsaturated ketones and aldehydes in undergoing addition reactions with nucleophilic reagents43. These reactions are initiated by nucleophilic attack at the carbon to the sulfone group ... 

Perhaps the most characteristic property of the carbon-carbon double bond is its ability readily to undergo addition reactions with a wide range of reagent types. It will be useful to consider addition reactions in terms of several categories (a) electrophilic additions (b) nucleophilic additions (c) radical additions (d) carbene additions (e) Diels-Alder cycloadditions and (f) 1,3-dipolar additions. 

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. 

Compound 874, as a representative of derivatives with an electron-withdrawing substituent at C-[1 of the vinyl group, is easily prepared by elimination of one benzotriazole from 2,2-/fo(benzotriazol-l-yl)ethyl methyl ketone 873. The stereoselective elimination catalyzed by NaOH gives exclusively the (E) isomer of derivative 874. Addition of nucleophiles to the double bond of vinyl ketone 874 followed by elimination of benzotriazole leads to a,P unsaturated ketones 875. Amines used as nucleophiles do not need any catalysis, but reactions with carbon and sulfur nucleophiles require addition of a base. The total effect is nucleophilic substitution of the benzotriazolyl group at the i-carbon of orji-iinsaturatcd ketone (Scheme 142) <1996SC3773>. 

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). 

Dideoxynucleosides show potent anti-retroviral activity against HIV-specific reverse transcriptase80-83. In particular, 2, 3 -dideoxy-3 -C-cyano-2 -substituted thymidine derivatives (33 A and 33 B) with a free 5 -hydroxy function (R1 = H) are potential inhibitors of the HIV-reverse transcriptase-promoted c-DNA synthesis. As these compounds have yet to be prepared by another method, the 3 -ene-nitrile 3284 was subjected to conjugate addition reactions with ammonia, primary amines, secondary amines and carbon nucleophiles. Most of these nucleophilic amine addition reactions give either the trans-isomer 33 A as the sole product (e.g., reaction with pyrrolidine, piperidine, morpholine), or as the major product along with the c/s-isomer (e.g., reaction with methylamine, benzylamine), except for the reaction with ammonia where the cts-isomer 33B is formed as the major product84. 

In Chapter 11 we continue our focus on organic molecules with electron-rich functional groups by examining alkynes, compounds that contain a carbon-carbon triple bond. Like alkenes, alkynes are nucleophiles with easily broken n bonds, and as such, they undergo addition reactions with electrophilic reagents. 

The nucleophilic character ofdialkyl sulfides is illustrated by their nucleophilic addition reaction with alkyl halides to form the corresponding sulfonium salts (35) (Scheme 13). Asymmetric sulfonium salts (36) have a tetrahedral configuration therefore, like the analogous chiral saturated carbon compounds, they can be resolved into optical enantiomers (see Chapter 6, p. 81). They are, however, generally less optically stable than sulfoxides, but in sulfonium salts the unshared electron pair can hold its configuration at ordinary temperatures, unlike nitrogen in quaternary ammonium salts, enabling their resolution to be achieved. 

When an unsymmetrical alkene undergoes an addition reaction with a compound E-Nu, the electrophile (E) will add to the carbon with the greater number of hydrogens, and the nucleophile (Nu) will add to the carbon with the fewer number of hydrogen substituents. 

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