Allylic sources

A procedure has been developed for the palladium-catalysed a-arylation of amides by aryl bromides using the zinc enolates of the amides. The reaction works well with bromoarenes carrying a variety of ring substituents and with bromopyridine. In addition, the reaction has been shown to be effective with morpholine amides to give products which are precursors for aldehydes and ketones.39 A new method has been reported for the allylation of aryl halides using homoallyl alcohols as the allyl source the palladium-catalysed reaction, which may be both stereo- and regio-sepecific, uses a retro-allylation reaction to form a a-allyl(aryl)palladium intermediate.40... 

Morken and Lavastre used the formation of a colored side product to identify catalysts for the allylation of /i-dicarbonyl compounds [8]. The researchers employed 1-naphthyl allyl carbonate 5 as an allyl source and the diazonium salt of fast red as an indicator. Formation of the active 7z>allyl complex furnishes C02 and 1-naphthoxide which deprotonates the 1,3-dicarbonyl compounds which can, in turn, react with the 71-allyl metal complex. 1-Naphthol is the only species in the reaction mixture that can react with the diazonium salt 6 to generate the bright red azo dye fast red. Thus the red color is indicative of successful formation of the active re-allyl complex (Figure 5.4.3). 

Catalytic asymmetric allylations of aldehydes or ketones are roughly classified into two methods, namely, those using chiral Lewis acid catalysts and those using chiral Lewis base catalysts. The former method uses less reactive allylsilanes or allylstannanes as the allyl source. The latter method requires allyltrichlorosi-lane or more reactive allylmetals. Both processes are applicable to the reactions with substituted allylmetal compounds or propargylation. 

The most widely used preparative method of allylindium(m) or propargylindium(lll) compounds is the oxidative addition of metallic indium or indium(l) halides to allylic or propargyl substrates.4 26 27 Allylic bromides and iodides serve as good allylic sources without any other activation. In the case of allylic chlorides, a proper additive such as lithium iodide is required to promote the oxidative addition. Allylic indium compounds prepared by oxidative addition of metallic indium are considered to exist as the sesquihalide structure (allyl jImXj), which has been... 

Allylic Sources Ambident Nucleophiles Better Donors Increase Reactivity Vinylogous Allylic Sources Allyiic Alkyne Sources... 

Resonance structures show us that either the double bond or the heteroatom can serve as an electron source. Because allylic sources can bite at two different sites they are called ambident nucleophiles. Usually the double bond is the attacking nucleophile the decision about which end of the allylic source attacks the electrophile will be discussed in Section 9.4. 

Which of the following, CH2=CH-0", CH2=CH-NR2, CH2=CH-C1, is the most reactive allylic source Which is the least ... 

Answer The best donor is the oxygen anion, so the best allylic source of the three is the enolate, CH2=CH-0 the next best is the enamine, CH2=CH-NR2. The least is the vinyl chloride, CH2=CH-C1, because chlorine is a very poor donor. 

Vinylogous allylic sources, Z-C=C-C=C or Z-C=C-C=0, commonly react at the center atom and therefore will be treated as a subset of this source. A few examples of these vinylogous allylic electron sources are, respectively, extended enolates, acetoacetates, and malonates. 

If we add a second pi bond perpendicular to an allylic system we create this rare electron source that should just be treated as a subset of the allylic sources. 

The pi bond is the electron source. For allylic sources, the electron pair donor stabilizes the resultant cation. The simple alkene reactivity trend reflects the stabilization of the resultant carbocation by alkyl substitution and delocalization with other double bonds. The ranking of simple double bonds as electron sources basically is the more substituted, the more reactive. 

Z Heteroatom lone pairs as nucleophiles RS- r CN- RO- Softer anions are more nucleophilic. If same atom, more basic, more Nu Substitutions Additions. Nucleophile vs. base decision See allylic sources... 

R-M Organo- metallics CHjLi CHaMgl (CH3)2Cu-Li+ The more ionic RM bond is more reactive Substitutions Additions. Deprotonates acidic H s See enolates (allylic sources)... 

C=C-Z Allylic sources Enolates C=C-0 Enamines C=C-NR2 Enol ethers C=C-OR The better donor on the pi bond is more reactive Substitutions Additions. Carbon vs. heteroatom decision Extended enolates. Allylic alkyne sources... 

Under equilibrium conditions (thermodynamic control), the allylic source adds to the polarized multiple bond (path AdN). However, the allylic source can also serve as a base and may deprotonate the sink, creating a mixture of sources and sinks and thus a messy statistical mixture of products. Clean products result if the source is just the deprotonated sink or if the sink has no acidic protons. With ketones, the equilibrium of the attack step favors the starting materials, and therefore the reaction goes to completion only if driven by a following elimination. In the next Adisj2 example, the source is the deprotonated sink. The product is an aldehyde-alcohol, or aldol, a name now used for the general process of an enol (acidic media) or enolate (basic) reacting with an aldehyde or ketone. 

Simple pi bonds are not good enough nucleophiles to react with nitriles. It is basically a case of little push and little pull, so no electron flow occurs. If the pi bond is made more nucleophilic by addition of a pi donor (making it an allylic source) then the... 

These deprotonations generate extended enoiates, which are vinylogous allylic sources. Deprotonation can also occur on the methyl next to the carbonyl in the following example. However, the extended enolate is more delocalized. Section 9.3 covers the regiochemistry and stereochemistry of enolate formation in more detail. 

Allylic Sources Reacting with L-C= Y Sinks, Acyiation... 

Allylic sources attack carboxyl derivatives such as esters almost exclusively on carbon by the path AdN, then Ep. As in Section 8.5.5, the enolate source should be the deprotonated sink or the sink should not be enolizable. A final proton transfer to give a resonance delocalized stable anion is frequently the driving force for the reaction. 

The carbon-carbon bond-forming step of the acid-catalyzed aldol reaction has an enol (allylic source) attacking a protonated carbonyl (which is just a lone-pair-stabilized carbocation). With those hints, give a mechanism for the acid-catalyzed aldol reaction. 

All allylic sources have the capability to act as a nucleophile on either 6- end of the source. Since the two ends of the allylic source commonly differ in electronegativity, the charge on each end differs. The two ends commonly differ in polarizability also. Therefore the Z end is usually much harder than the softer C end. For soft electrophiles, the soft-soft component is most important therefore the atom with the greatest polarizability will be the best nucleophile. For hard electrophiles, the hard-hard component is most important, therefore the atom with the largest partial minus will be the best nucleophile (charge control). Solvation is also a hard-hard interaction, and the tighter the solvation around the Z end, the more hindered and poorer the Z nucleophile is. 

With anionic allylic sources, highly polar aprotic solvents increase the amount of lone pair alkylation because poor solvent stabilization of the anion leaves the heteroatom end less hindered by solvent. Conversely, groups bound to the heteroatom increase the steric hindrance about it, and therefore decrease the tendency toward heteroatom alkylation. For example, enamines (R2N-C=C) tend to alkylate on carbon rather than nitrogen (as shown in Section 8.4.5). 

In the following list are the extremes for the alkylation reaction of allylic sources however, product mixtures occur rather often. 

The basic media exceptions can be easily understood if we invoke HSAB theory and realize that the kinetic and thermodynamic products are different. As L becomes a poorer donor, the partial plus on the acyl carbon increases, making it harder. Acylation on the heteroatom of the allylic source is fast for acyl halides and anhydrides where the acyl carbon is harder (greater partial plus) than the acyl carbon of esters. If the reaction is under kinetic control (allylic source added to an excess of acyl halide or anhydride), the Z-acylated product is formed however, if equilibration occurs (excess of allylic source), the product will be the C-acylated, thermodynamic product. 

In acidic media, the electron sink is most often the carbocation produced from protonating the acylating agent, and therefore the sink is very hard. Attack by the Z end (harder end) of the allylic source is very fast. For enols, the Z-acylated kinetic product can be isolated. Since the Z-acylated enol is itself an allylic source (but weaker), it can be forced by more vigorous conditions to equilibrate to the more stable C-acylated product. For enamines, the Z-acylated enamine is a good acylating agent any excess of enamine will attack it and equilibrate it to the more stable C-acylated product. 

We need to record only that which has changed from our original observations. We now have a new source, the delocalized anion just formed. This enolate anion is nucleophihc on carbon 2, just what is needed for our addition process. Resonance forms indicate the ambident nature of the enolate, an allylic source ... 

There are other paths that fit the medium, sources and sinks protonation of an anion, p.t., and addition to a polarized multiple bond by the oxygen of the enolate by AdgS or AdN2. There are two sites that can serve as a base or as a nucleophile on this ambident allylic source. We have three choices to evaluate proton transfer to oxygen,... 

Any of the three possible anionic atoms in the resonance forms above could serve as our source, but usually allylic sources attack on carbon because it is a softer, better nucleophile, and the product preserves the strong carbonyl double bond. 

The ester enolate is an allylic source that can serve as a base or a nucleophile. The original ester has acidic hydrogens within range of the enolate. The ester carbonyl is an electrophilic sink (a polarized multiple bond with attached leaving group). 

Note the preferential reaction at the anomeric hydroxyl. The method is also effective for the protection of primary and secondary alcohols. A modification of this approach which uses f-Bu0C02CH2CH=CH2as the allyl source selectivity monoalkylates a tertiary hydroxyl in the erythronolide derivative. 

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