Carbonyl carbon, nucleophilicity

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

Electron release from nitrogen stabilizes the carbonyl group of amides and decreases the rate at which nucleophiles attack the carbonyl carbon. Nucleophilic reagents attack electrophilic sites in a molecule if electrons are donated to an electrophilic site in a molecule by a substituent, then the tendency of that molecule to react with external nucleophiles is moderated. 

Step 1 Make a new bond between a Anunonia adds to the carbonyl carbon. nucleophile and an electrophile. 

Turning to the reagent, this section has shown that sodium nitrite in the presence of acid is a source of the electrophilic nitrosyl cation. In our example, it appears that attack has occurred a to the carbonyl function. Do we know anything about how electrophiles might attack ketones in this manner Or, to put it differently, how do we make the a-carbonyl carbon nucleophilic ... 

Formation of ketones. Ketones can be prepared by the carbonylation of halides and pseudo-halides in the presence of various organometallic compounds of Zn, B, Al, Sn, Si, and Hg, and other carbon nucleophiles, which attack acylpalladium intermediates (transmetallation and reductive elimination). 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

Section 17 2 The carbonyl carbon is sp hybridized and it and the atoms attached to It are coplanar Aldehydes and ketones are polar molecules Nucleophiles attack C=0 at carbon (positively polarized) and electrophiles especially protons attack oxygen (negatively polarized)... 

The step m which Ihe nucleophile attacks Ihe carbonyl carbon is rate determining m bolh base calalyzed and acid calalyzed nucleophilic addilion In Ihe base calalyzed mechanism Ihis is Ihe lirsl step... 

Electron release from nitrogen stabilizes the carbonyl group of amides and decreases the rate at which nucleophiles attack the carbonyl carbon... 

Monomer Reactivity. The poly(amic acid) groups are formed by nucleophilic substitution by an amino group at a carbonyl carbon of an anhydride group. Therefore, the electrophilicity of the dianhydride is expected to be one of the most important parameters used to determine the reaction rate. There is a close relationship between the reaction rates and the electron affinities, of dianhydrides (12). These were independendy deterrnined by polarography. Stmctures and electron affinities of various dianhydrides are shown in Table 1. 

This comparison is further demonstrated by observing that the chemistry of both trigonal boron and carbonyl carbon are strongly influenced by the ready acceptance of attacking nucleophiles. 

The study of the chemistry of carbonyl compounds has shown that they can act as carbon nucleophiles in the presence of acid catalysts as well as bases. The nucleophilic reactivity of carbonyl compounds in acidic solution is due to the presence of the enol tautomer. Enolization in acidic solution is catalyzed by O-protonation. Subsequent deprotonation at carbon gives the enol ... 

The addition of carbon nucleophile, including organometallic compounds, enolates, or enols, and ylides to carbonyl gro is an important method of formation of carbon-carbon bonds. Such reactions are- ctremely important in synthesis and will be discussed extensively in Part B. Here, we will examine some of the fundamental mechanistic aspects of addition of carbon nucleophiles to carbonyl groups. 

SECTION 8.3. ADDITION OF CARBON NUCLEOPHILES TO CARBONYL GROUPS... 

Enolates can also serve as carbon nucleophiles in carbonyl addition reactions. The addition reaction of enolates with carbonyl compounds is of very broad scope and is of great synthetic importance. Essentially all of the enolates considered in Chapter 7 are capable of adding to carbonyl groups. The reaction is known as the generalized aldol addition. 

The reactivity of fluoro(organyl)phosphanes depends on the nucleophilicity of phosphorus For mstance the phosphanes may add to the carbonyl carbon to form phosphiniio phosphoranes (equation 36) or may react with acid fluondes to form acyldifhiorophosphoranes [37] (equation 37)... 

The step in which the nucleophile attacks the carbonyl carbon is rate-detennining in both base-catalyzed and acid-catalyzed nucleophilic addition. In the base-catalyzed mechanism this is the first step. 

The product is a hemithioacetal. In the rate-determining step, the general acid HA donates a proton to the carbonyl oxygen, thus assisting the nucleophilic attack of the thiol on the carbonyl carbon. 

When written in this way it is clear what is happening. The mechanisms of these reactions are probably similar, despite the different p values. The distinction is that in Reaction 10 the substituent X is on the substrate, its usual location but in Reaction 15 the substituent changes have been made on the reagent. Thus, electron-withdrawing substituents on the benzoyl chloride render the carbonyl carbon more positive and more susceptible to nucleophilic attack, whereas electron-donating substituents on the aniline increase the electron density on nitrogen, also facilitating nucleophilic attack. The mechanism may be an addition-elimination via a tetrahedral intermediate ... 

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