Carbonylation nucleophilic attack

Attack of nucleophiles on carbonyl Nucleophilic attack on saturated Elimination reactions chi 7... 

In a large number of carbonyls nucleophilic attack seems more likely at the carbonyl-carbon than at the metal. There is often good evidence from products for such attack at the ligand, and these examples are therefore discussed in a later section on reactions of co-ordinated ligands (p. 301). 

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

Step 1 The amine acts as a nucleophile attacking the carbonyl group and forming a C—N bond... 

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... 

As an electron withdrawing group on a carbon-carbon double bond a carbonyl group renders the double bond susceptible to nucleophilic attack... 

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

Protonation of the carbonyl oxygen as emphasized earlier makes the carbonyl group more susceptible to nucleophilic attack A water molecule adds to the carbonyl group of the protonated ester m step 2 Loss of a proton from the resulting oxonium ion gives the neutral form of the tetrahedral intermediate m step 3 and completes the first stage of the mechanism... 

All these facts—the observation of second order kinetics nucleophilic attack at the carbonyl group and the involvement of a tetrahedral intermediate—are accommodated by the reaction mechanism shown m Figure 20 5 Like the acid catalyzed mechanism it has two distinct stages namely formation of the tetrahedral intermediate and its subsequent dissociation All the steps are reversible except the last one The equilibrium constant for proton abstraction from the carboxylic acid by hydroxide is so large that step 4 is for all intents and purposes irreversible and this makes the overall reaction irreversible... 

The amide is activated toward nucleophilic attack by protonation of its carbonyl oxygen The cation produced m this step is stabilized by resonance involving the nitro gen lone pair and is more stable than the intermediate m which the amide nitrogen is protonated... 

FIGURE 27 19 Proposed mechanism of hydrolysis of a peptide catalyzed by carboxypeptidase A The peptide is bound at the active site by an ionic bond between its C terminal ammo acid and the positively charged side chain of arginine 145 Coordination of Zn to oxygen makes the carbon of the carbonyl group more positive and increases the rate of nucleophilic attack by water... 

Another very important reaction initially involving nucleophilic attack on an aldehyde carbonyl is the Wittig reaction. An yUd adds to the carbonyl forming a betaine intermediate which then decomposes to produce an olefin and a tertiary phosphine oxide. 

Lithium amides of primary / fZ-alkylamines yield N-(/ f2 -alkyl)-0-(/ f2 -butyl)hydroxylamines, whereas lithium amides of primary alkylamines yield A/-alkylbenzamides and LiOO—due to nucleophilic attack on the carbonyl group (245). 

A related but distinct rhodium-catalyzed methyl acetate carbonylation to acetic anhydride (134) was commercialized by Eastman in 1983. Anhydrous conditions necessary to the Eastman acetic anhydride process require important modifications (24) to the process, including introduction of hydrogen to maintain the active [Rhl2(CO)2] catalyst and addition of lithium cation to activate the alkyl methyl group of methyl acetate toward nucleophilic attack by iodide. 

Acyl derivatives of azoles containing two different environments of nitrogen atoms can rearrange. For example, 1-acyl-1,2,3-triazoles are readily isomerized to the 2H-isomers in the presence of triethylamine or other bases the reaction is intermolecular and probably involves nucleophilic attack by N-2 of one triazole on the carbonyl group attached to another (74AHC(16)33). 

Nucleophilic attack on ring atoms of large heterocycles is largely confined to saturated systems, saturated parts of partially unsaturated systems, and to carbonyl functions and the like. These reactions are not fundamentally different from those of corresponding acyclic systems, except for transannular reactions. 

Anions of heterocyclics may attack heterocumulenes to set up systems which can incorporate new atom sequences into the ring by nucleophilic attack on a ring site (such as a carbonyl group). Scheme 32 gives an example (80AG(E)466). 

Ortho esters are among the few derivatives that can be prepared from acids and esters that protect the carbonyl against nucleophilic attack by hydroxide or other... 

The effect of conformation on reactivity is intimately associated with the details of the mechanism of a reaction. The examples of Scheme 3.2 illustrate some of the w s in which substituent orientation can affect reactivity. It has been shown that oxidation of cis-A-t-butylcyclohexanol is faster than oxidation of the trans isomer, but the rates of acetylation are in the opposite order. Let us consider the acetylation first. The rate of the reaction will depend on the fiee energy of activation for the rate-determining step. For acetylation, this step involves nucleophilic attack by the hydroxyl group on the acetic anhydride carbonyl... 

A) Protonation followed by nucleophilic attack on the protonated carbonyl group ... 

The stereoselectivity of organometallic additions with carbonyl compounds fits into the general pattern for nucleophilic attack discussed in Chapter 3. With 4-r-butylcyclohex-anone, there is a preference for equatorial approach but the selectivity is low. Enhanced steric factors promote stereoselective addition. 

Protecting groups are generally formed by nucleophilic attack on the carbonyl group and the rate of this process is determined by steric and electronic factors associated with the ketone. In steroid ketones steric effects are usually more important due to the rigid tetracychc skeleton. 

Polyfluoroalkyl- andperfluoroalkyl-substituted CO and CN multiple bonds as dipolarophiles. Dmzo alkanes are well known to react with carbonyl compounds, usually under very mild conditions, to give oxiranes and ketones The reaction has been interpreted as a nucleophilic attack of the diazo alkane on the carbonyl group to yield diazonium betaines or 1,2,3 oxadiazol 2 ines as reaction intermediates, which generally are too unstable to be isolated Aromatic diazo compounds react readily with partially fluorinated and perfluorinated ketones to give l,3,4-oxadiazol-3-ines m high yield At 25 °C and above, the aryloxa-diazolines lose nitrogen to give epoxides [111]... 

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