Enolate enamines

Difunctional target molecules are generally easily disconnected in a re/ro-Michael type transform. As an example we have chosen a simple symmetrical molecule, namely 4-(4-methoxyphenyl)-2,6-heptanedione. Only p-anisaldehyde and two acetone equivalents are needed as starting materials. The antithesis scheme given helow is self-explanatory. The aldol condensation product must be synthesized first and then be reacted under controlled conditions with a second enolate (e.g. a silyl enolate plus TiCl4 or a lithium enolate), enamine (M. Pfau, 1979), or best with acetoacetic ester anion as acetone equivalents. 

As shown in Scheme 2, two heteroatom-carbon bonds are constructed in such a way that one component provides both heteroatoms for the resultant heterocycle. By variation of X and Z entry is readily obtained into thiazoles, oxazoles, imidazoles, etc. and by the use of the appropriate oxidation level in the carbonyl-containing component, further oxidized derivatives of these ring systems result. These processes are analogous to those utilized in the formation of five-membered heterocycles containing one heteroatom, involving cyclocondensation utilizing enols, enamines, etc. 

The Nitrogen Analogs of Enols and Enolates Enamines and Imine Anions... 

Silyl enolates, enamines, or vinyl sulfides can serve as trapping agents. 

Allylic Substitutions with Nonstabilized Enolates, Enamines and Organozinc Compounds... 

SECTION 1.9. THE NITROGEN ANALOGS OF ENOLS AND ENOLATES— ENAMINES AND IMINE ANIONS... 

Nu = NaBH3CN, RLi, RMgX (R = alkyl, aryl, vinylic, alkynyl), ketone enolate, enamine, malonate... 

This section describes the additions of stabilized carbon nucleophiles, such as cyanide, malonate, ketone enolates, enamines, etc., to alkenic ir-systems. These reactions are highly useful in organic synthesis since they are all carbon-carbon bond-forming reactions, and therefore have been used extensively in organic chemistry. 

In origin, the Mannich reaction is a three-component reaction between an eno-lizable CH-acidic carbonyl compound, an amine, and an aldehyde producing / -aminocarbonyl compounds. Such direct Mannich reactions can encompass severe selectivity problems since both the aldehyde and the CH-acidic substrate can often act as either nucleophile or electrophile. Aldol addition and condensation reactions can be additional competing processes. Therefore preformed electrophiles (imines, iminium salts, hydrazones) or nucleophiles (enolates, enamines, enol ethers), or both, are often used, which allows the assignment of a specific role to each car-... 

A second important reaction of silyl enol ethers is their reaction with Enolates, enamines, and silyl enol strong electrophiles, which is depicted schematically in Figure Si3.3. ethers all exhibit similar reactivity... 

Q Show how enols, enamines, and enolate ions act as nucleophiles. Give mecha- Problems 22-60, 61, and 65... 

Alkylations of enolates, enamines, and silyl enol ethers of cyclohexanone usually show substantial preference for axial attack. The enamine of 4-f-butylcyclohexanone, which has a fixed conformation because of the i-butyl group, gives 90% axial alkylation and only 10% equatorial alkylation with n-Prl. 

In the gas phase the free energy of protonation of A,N-dimethylvinylamine (equation 48) is — 220.0 kcal mol-1 64. As discussed in Section II.A.4, protonation occurs at Cp, as shown506 112,113. The free energies of protonation of methyl vinyl ether and methyl vinyl sulfide are —198.8 and —198.6 kcal mol-1, respectively these substances also are protonated at C/14. Far more basic than any of these is the enolate of acetaldehyde (vinyloxide-) for which C-protonation is accompanied by AG°(g) = —359 kcal mol-1 115. Thus, the gas-phase reactivity order is enolates > enamines en-olethers enols vinyl sulfides. (For the present purpose, we ignore the real, but smaller, differences in reactivity between enols, their ethers and vinyl sulfides.)... 

Common error alert A nucleophilic alkene always reacts with an electrophile such that the C less able to be electron-deficient makes the new bond. In alkenes directly substituted with lone-pair-bearing heteroatoms (enolates, enamines, enols, enol ethers), the /3-carbon (not attached to heteroatom) is nucleophilic, and the a-carbon (attached to heteroatom) is not. In alkenes substituted only with alkyl groups,... 

Enolate Enamine Enol ether Vinyl halide... 

General discussion ofenols and enolates Formation of specific enol equivalents Lithium enolates, enamines and silyl enol ethers Enamines Silyl enol ethers... 

Lithium enolates, enamines and silyl enol ethers... 

We shall discuss further aspects of the aldol reaction in the next two chapters where we shall see how to control the enolisation of unsymmetrical ketones, and how to control the stereochemistry of aldol products such as 121. We shall return to a more comprehensive survey of specific enol equivalents in chapter 10. In this chapter we are concerned to establish that chemoselective enolisation of esters, acids, aldehydes, and symmetrical ketones can be accomplished with lithium enolates, enamines, or silyl enol ethers, and we shall be using all these intermediates extensively in the rest of the book. 

Keywords Allyl alcohol, Allylamine, Aza-allyl, Azomethine, BINAP, BIPHEMP, Citronellal, Cobalt, DIOP, Enol, Enamine, Imine, Isomerization, Kinetic resolution. Nitrogen-triggered, Rhodium, Ruthenium... 

Some statistics the series, now in its 35th year, has covered so far more than 50 functional groups, both simple and complex (e.g. enols, enamines) in one-hundred main volumes and eight update volumes which contain 83 500 pages. More than 1500 authors from many countries in five continents have contributed 1314 review chapters, which cover an extensive part of organic chemistry. 

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