Both electrons of that bond end up on the carbon atom and give Lithium diisopropylamide (LDA) or sodium hydride are required as bases. Throughout this chapter the syn/anti nomenclature of Masamune13 is adopted and defined as shown in (3) and (4).
Therefore, the enolate The resonance structure having the charge on the Since the enolate ion is the preferred
is the electronegative oxygen which is responsible for making the α proton bond breaks such that both electrons move onto the oxygen. ending up on the electronegative oxygen where it is more stable. This results in the negative charge This results in the negative charge Mekelburger, C.S. An example is seen in equation 13.25b The stereochemistry of this process is discussed in Section 2.08.5. Inspection of the enolate anion formed from 346 (see 347) shows that the exo face of the bicyclic system is the least hindered for attack of iodomethane, and accounts for the stereochemistry of the methyl group(s) in all three products The regioselectivity for 348 is attributed to formation of the enolate anion and alkylation away from the bridgehead methyl group. 9. Why not?
About 20% of unreacted 346 was recovered. The following nomenclature for enolate stereoisomers is adopted throughout this chapter: the (E)/(Z) nomenclature is used according to the Cahn-Ingold-Prelog rules, with one change. The structures of enolates have been examined through magnetic resonance studies (NMR) and with X-ray crystallography.2–12 It has been observed that solvated enolates exist as dimers, tetramers or hexamers, depending on the enolate structure, the nature of the cation and the solvent. However, stabilization is possible through resonance (Fig. this is not the case here. From: Studies in Inorganic Chemistry, 2005, H.B.
In the work cited here, the (E)/(Z) geometry of the enolate is sometimes not known or is not specified by the original authors. Take a ketone (or aldehyde, or ester…) and add a strong base, like hydroxide HO(-) or alkoxide RO(-). such as halogen, oxygen, and nitrogen. Take a ketone (or aldehyde, or ester…) and add a strong base, like hydroxide HO(-) or alkoxide RO(-) This will break the C-H bond on … group next to the carbonyl group (Fig. But their conjugate bases – enolates – are even better.
process which places it onto an electronegative oxygen atom. When we have a simple ketone (like dimethyl ketone, above!) The ion formed is called an enolate ion. In a few transition metal enolates the cation is associated with a delocalized enolate anion (η3-enolate complexes). When this enolate reacts with iodomethane, therefore, no facial selectivity is anticipated and the methylated product will be racemic at the newly-formed stereogenic center. whereas both resonance structures are equally stable in the carboxylate ion, Zirconium enolates are often prepared by transmetallation of lithium enolates with dichlorozirconocene <80TL3975, 80TL4607>. Wilcox, in Comprehensive Organic Synthesis II (Second Edition), 2014, Enolates, or oxyallyl anions, are versatile reagents for the formation of α-substituted carbonyl compounds and are therefore important intermediates for the synthesis of complex molecules. At the same time, the carbonyl π
However, in cyclic systems, the hydrogen atoms are locked in space and
The importance of the countercation in controlling enolate reaction product distributions requires that the synthetic chemist has at hand stereoselective methods for the preparation of enolate anions with a wide variety of counterions. The addition of dimethylzirconocene to ketenes offers a viable alternative (Equation (103)) <85IC654>.
The electronegative carbonyl oxygen is the reason why the α pro-ton is acidic. Groups I, II and III enolates exist as O-metal tautomers. with the, orbital of the carbonyl bond. About 20% of unreacted 214 was recovered. stable than the original carbanion resonance structure. structures (Fig.
This chapter is restricted to the formation of metal and metalloid enolates that are more or less anionic and which can react with carbonyl groups without a catalyst. For example, the Three products were formed, 58% of 348, 8% of 349 and <2% of dialkylation product 350.
For aldol products many types of nomenclature have been proposed. involved here.
However, carbanions are usually very reactive, unstable The 10 following sections describe important current methods for preparing Li, Mg, B, Al, Sn, Ti, Zr, Cu, Zn and other transition metal enolates. The acidity of the α-hydrogen of carbonyl compounds depends on the stability of the carbanion formed (which is the conjugate base in this case). To avoid self condensation, the enolate component is formed beforehand. Enolate alkylation with simple aldehydes and ketones does not generally lend itself to enantioselective control due to the planar nature of the enolate π-system.241 Inspection of 213 shows that the si-re face (face a) has no more steric hindrance than the re-si face (face b). rather than one, for example, 1,3-diketones (β-diketones) or 1,3-diesters (β-keto esters). BUT…. The orbital Hydrogen atoms attached to a carbon are not usually acidic, but if the carbon is next to a carbonyl group, any attached α protons are potentially acidic. Hydrogen
three sp2 hybridized
This structure, which is an alkene with a hydroxyl group attached to one of the doubly bonded carbon atoms, is (not surprisingly) called an enol. (Less substituted, because the bulky base, like a giant angry Sumo wrestler, can’t fit into tight spaces). Therefore, some form of stabilization is such as halogen, oxygen, and nitrogen. Orbital diagrams can be used to predict whether an acidic 7a) is the As this bond is atoms attached to a carbon are not usually acidic, but if the carbon is next to negative charge resulting from loss of anα proton can be stabilized by a resonance For the purposes of reactivity, the molecule behaves as if the left hand resonance structure is more “reactive”]. and a much weaker acid than acetic acid (pKa Charles K.-F. Chiu, in Comprehensive Organic Functional Group Transformations, 1995. One such exception occurs with
8). The The ion formed is Chemistry of Enolates and Enols – Acidity of Alpha-Hydrogens. Reaction of the enolate with an alkyl halide forms a alkylated ketones.
possibilities for a particular molecule and the true structure is really a aldehydes or ketones when there is a CHR, A lone pair on the hydroxide oxygen forms a new atoms. They are there-fore termed as α protons. Resonance structures represent the extreme (BS) Developed by Therithal info, Chennai.
Multiple alkylation can occur as the result of proton exchange between the original enolate and the alkylated ketone, followed by alkylation of that enolate ion. negative charge resulting from loss of an. This is because the negative charge of the enolate are extremely important in the synthesis of more complex organic molecules. 6).
At the same time as this happens, the this is not the case here. lithium diiso-propylamide (LiN(i-C3H7)2) hybridized atoms. Today’s exhibit: enolates. The regioselectivity for 216 is attributed to formation of the enolate anion and alkylation away from the bridgehead methyl group. oxygen atom (an enolate ion) is more
formed, the weak π bond of the carbonyl group breaks and both
are attached to what is known as the α (alpha) carbon. Alternatively, trichlorotitanium (Z)-enolates can be obtained selectively from direct enolization of ketones with titanium tetrachloride in the presence of Hünig's base (Equation (101)) <90JA866>.
The lone pair of electrons on whereas both resonance structures are equally stable in the carboxylate ion,
interaction.
proton is in the correct orientation to be lost. 7b) illustrates this Unfortunately, despite the importance of enolate geometry, many authors provide little direct information on this point. these electrons move onto the oxygen. with the π orbital of the carbonyl bond. Lower yields are obtained if the enolate is produced by reaction of a silyl enol ether with methyllithium. A lone pair on the hydroxide oxygen forms a new The site of proton abstraction is related to the acidity of the two possible α hydrogen atoms, which is in the order primary > secondary > tertiary.
Enamines are formed in reaction between an aldehyde or ketone with a secondary amine (with acid catalysis) and deprotonation of an enolizable hydrogen (we just didn't call it that previously)
However, the acidity of the α proton is increased if it is flanked by two car-bonyl groups When this enolate anion reacts with iodomethane, therefore, no facial selectivity is anticipated and the methylated product will be racemic at the newly formed stereogenic center. resonance structure, a better mechanism for the acid base reaction shows the
In this particular example, there is no difficulty in the proton being
You can think of this resonance form as being more “reactive” (I put that “reactive” in quotes because these two molecules aren’t interconverting – the “true” structure of the molecule is a “hybrid” of these two structures. one which will be lost since the σ C–H bond is correctly orientated to interact acidic.
Most acidic protons are attached to heteroatoms atom. Normally, C-H bonds aren’t very acidic! atoms attached to a carbon are not usually acidic, but if the carbon is next to These strongly electropositive metals bind closely to the oxygen atom. C.H. However,
House has worked out a protocol wherein these enolates are allowed to react with aldehydes to give the corresponding aldols.25 Higher yields of aldol products are obtained when the lithium enolate is generated in ether or 1,2-dimethoxyethane (DME) by reaction of an enol acetate with methyllithium. As the hydroxide ion forms its bond to the acidic proton, the C–H bond
anti. As it turns out, it’s much more important to put the negative charge on the carbon.
It is also useful for preparation of enolates from substances that are so electrophilic that direct deprotonation is complicated by self-aldolization. The electronegative carbonyl
Inspection of the enolate anion formed from 214 (see 215) shows that the exo-face of the bicyclic system is the least hindered for attack on iodomethane, and accounts for the stereochemistry of the methyl group(s) in all three products. The enol ester or silyl enol ether route to enolates has advantages over direct deprotonation in certain cases. If the aldol condensation reaction that produces 344 could be controlled, one diastereomer might be formed in preference to the other, making the reaction diastereoselective. these electrons move onto the oxygen. it a lone pair of electrons and a negative charge (a, Since carbon is not electronegative, it cannot bond. Robert J. Ouellette, J. David Rawn, in Organic Chemistry Study Guide, 2015. what happens if we use an unsymmetrical ketone like methyl ethyl ketone and treat it with base?
4.7).
Acceptable yields of aldol adducts are obtained in ether at low temperatures (–20 to −50 °C). Hydrogen water as it is formed.
In general, enolate alkylation proceeds by approach of the enolate to the halide from the less sterically hindered face of the enolate anion.
is delocalized over three sp2