Nucleophilic on carbonyl group

Attack of nucleophiles on carbonyl groups ch6, ch9, chl2, chl4 Attack of nucleophiles on double bonds conjugated with carbonyl groups chlO... 

Ring formations by reactions of a 7V-nucleophile on carbonyl groups or their equivalents are shown in Scheme 59, 60 and 61. The most familiar application, reductive amination, was used in the synthesis of azasugar derivative 147 from a diol precursor as shown in Scheme 59 <04TL5751>. 

Nucleophilic substitution on carbonyl groups carboxylic acid derivatives... 

NUCLEOPHILIC SUBSTITUTION ON CARBONYL GROUPS CARBOXYLIC ACID DERIVATIVES... 

Nucleophilic attack on carbonyl group 86 - 90 on phosphoryl and sulfuryl groups 89,90,260-266 on saturated carbon 90,91 Nucleophilic catalysis 61, 84, 85 examples with enzymes 45, 85, 100, 101,311... 

Pyridine is a reasonable nucleophile for carbonyl groups and is often used as a nucleophilic catalyst in acylation reactions. Esters are often made in pyridine solution from alcohols and acid chlorides (the full mechanism is on p. 000 of Chapter 12). 

The Z E ratio was found to vary considerably as the bulk of SiR3 group increased (Table 16) and this led to the development of an approach model to rationalize the relative energies of the transition states in the first steps or fc, 255,275. Attack of nucleophiles on carbonyl compounds occurs in the plane of the C-0 n bond with a... 

The important part of TPP is the five-membered ring, in which a carbon is found between a nitrogen and a sulfur. This carbon forms a carbanion and is extremely reactive, making it able to perform a nucleophilic attack on carbonyl groups, leading to decarboxylation of several compounds in different pathways. 

Nucleophilic attack on carbonyl groups leaving group Kinetics and mechanism chi 2... 

But just a moment—we ve overlooked an important point. We have sometimes used anions as nucleophiles (for example when we made acid anhydrides from acid chlorides plus car-boxylate salts, we used an anionic nucleophile RCO2) but on other occasions we have used neutral nucleophiles (for example when we made amides from acid chlorides plus amines, we used a neutral nucleophile NH3). Anions are better nucleophiles for carbonyl groups than are neutral compounds so we can choose our nucleophilic reagent accordingly. 

In Chapter 11 we showed you how acetals can be used as base-stable protective groups to prevent nucleophiles attacking carbonyl groups. The acetals we chose to use were cyclic compounds known as dioxoianes, for a very good reason cyclic acetals are more resistant to hydrolysis than their acyciic counterparts. They are also easier to make—they form quite readily, even from ketones. Again, we have entropic factors to thank for their stability. For the formation of an acyclic acetai (below on the left), three molecules go in and two come out, but for a cyclic one, a cyclic acetai, two molecules go in (ketone plus diol) and two molecules come out (acetal plus water), so the usually unfavourable AS factor is no longer against us. 

A proton is, of course, positively charged, so electrostatic attraction is the more important factor in nucleophilicity towards or The carbonyl group too has a substantial positive charge on the carbon atom, arising from the uneven distribution of electrons in the C=0 7t bond, and reactions of nucleophiles with carbonyl groups are also heavily influenced by electrostatic attraction, with HOMO—LUMO interactions playing a smaller role. 

This chapter is about deliberately getting nucleophilic attack by enols and enolates on carbonyl groups of aldehydes or ketones (the aldol reaction in the first half of the chapter) or on acylating agents (the second half of the chapter). 

There is some material of relevance in a review on chiral titanium complexes for the enantioselective addition of nucleophiles to carbonyl groups , in a short review on stereoselective transformations mediated by chiral CpM (M = Ti, Zr, Hf) complexes, and in a review on the preparation of organoaluminium and organomagnesium metallacycles from titanium and zirconium... 

The carbonyl unit carbonyl (C=0) is the functional group for aldehydes and ketones as well as esters (see Chapter 5, Section 5.9). All discussions in previous chapters focused on the carbonyl group and acyl addition or acyl substitution reactions with nucleophiles. The carbonyl group is electron withdrawing with respect to the attached carbon atoms in an aldehyde or ketone. Therefore, the carbonyl group will induce a dipole in the adjacent carbon (the a-carbon is 6-), which in turn leads to a dipole between that carbon and its attached hydrogen (the a-proton), as shown in 1. This so-called a-hydrogen or a-proton is 5f. 

Some reactions of thiamine, such as decarboxylation of a-oxocarboxylic acids, are features of primary metabolism (decarboxylation of pyruvic acid to acetaldehyde in glycolysis and transformation of pyruvic acid to acetyl-CoA prior to its entry into the citric acid cycle) that depend on thiamine diphosphate as a coenzyme. The thiamine ring has an acidic hydrogen and is thus capable of producing the carbanion that acts as a nucleophile towards carbonyl groups. Analogous reactions proceed non-enzymatically and can thus be included among the so-called... 

Note that the new Nu-C bond is made up entirely of the electron pair of the nucleophile. The transformation is reminiscent of an Sn2 reaction. In that process, a leaving group is displaced. Here, an electron pair is moved from a shared position between carbon and oxygen to one solely on the oxygen atom. Additions of strongly basic nucleophiles to carbonyl groups typically follow the nucleophilic addition-protonation pathway. 

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