Enolates preparation by deprotonation

Enolate Preparation by Deprotonation of Iron-Acyl Complexes a-Deprotonation of Iron-Acyl Complexes... 

Most of the work in this area has concerned complexes racemic at iron. Section D.1.3.4.2.5.1.1. details methods for the preparation and resolution of enantiomerically pure iron acyl complexes. The details of alkylation reactions (see Section 1.1.1.3.4.1.3.) and aldol reactions (see Section 1.3.4.2.5.1.2.) of these and other iron acyl enolates are presented later with examples utilizing enantiomerically pure complexes indicated therein. Table 1 illustrates the scope of iron-acyl enolates prepared by deprotonation of complex 10 and its analogs. 

Enolates prepared by deprotonation of carboxylic acid derivatives can also undergo elimination to yield ketenes. This is rarely seen with amides, but esters, thiolesters, imides, or N-acylsulfonamides can readily decompose to ketenes if left to warm to room temperature (Scheme 5.58). At -78 °C, however, even aryl esters can be converted into enolates stoichiometrically without ketene formation [462, 463],... 

Iron-acyl enolates such as 1, 2, and 3 react readily with electrophiles such as alkyl halides and carbonyl compounds (see Houben-Weyl, Vol. 13/9a p418). The reactions of these enolatc species with alkyl halides and similar electrophiles are discussed in Section D.1.1.1.3.4.1.3. To date, only the simple enolates prepared by a-deprotonation of acetyl and propanoyl complexes have been reacted with ketones or aldehydes. 

An excellent synthetic method for asymmetric C—C-bond formation which gives consistently high enantioselectivity has been developed using azaenolates based on chiral hydrazones. (S)-or (/ )-2-(methoxymethyl)-1 -pyrrolidinamine (SAMP or RAMP) are chiral hydrazines, easily prepared from proline, which on reaction with various aldehydes and ketones yield optically active hydrazones. After the asymmetric 1,4-addition to a Michael acceptor, the chiral auxiliary is removed by ozonolysis to restore the ketone or aldehyde functionality. The enolates are normally prepared by deprotonation with lithium diisopropylamide. 

The /(-titanium enolate was prepared by deprotonation with TMP-MgBr, followed by reaction with (/-PrO)3TiCl in the presence of HMPA. The TS for addition is also dominated by a polar effect and gives and 2,2 -anti product. 

Bromide 280 (derived by bromination of silyl enol ether 270) undergoes both zinc- and cerium-mediated cleavage under mild and essentially neutral conditions, and was used to prepare the nucleoside-containing C-glycoside 282 (Scheme 73) [ 112,113], The aldehyde 281 used in this transformation was exceptionally sensitive to basic conditions which completely precluded use of a conventional enolate obtained by deprotonation of ketone 265 (Sect. 4.3.1). 

Lactols and their acetals can be transformed easily into their 2-arylsulfonyl derivatives 337 by reaction with a sulfinic acid under Lewis acid activation. The corresponding organolithiums are prepared by deprotonation with n-BuLi or LDA and, after reaction with electrophiles, a /(-elimination of sulfinic acid afforded a cyclic a-substituted enol ether514,547,548. 2-Lithio-2-(arylsulfonyl)tetrahydropyrans equilibrated to give mainly the anomer with the lithium atom at the equatorial position549. 

A /S-substituted enol ether bearing a typical protecting group, such as tetrahydropyranyl in compound 554, has been prepared by deprotonation with s-BuLi and trapped with Mel... 

Alkylation of fl-aryleyclopentanones. Addition of 10 mole% of CuCN to the lithium enolate prepared from /3-arylcyclopentanones and LDA increases the amount of the less stable product of alkylation. Polyalkylation is also suppressed. Similar results are obtained when methyl- or phenylcopper is added to the enolate prepared by alkyUithium cleavage of trimethylsilyl enol ethers. The mechanism by which Cu(I) influences these alkylations is not as yet understood. The regiospecificity of enolate formation in the example Illustrated in equation (I) has been attributed to a directing efiect of the proximate phenyl group. This effect is also observed in the deprotonation of -arylcyclohexanones. Quantitative, but not qualitative, differences exist between five- and six-membered rings, probably because of conformational differences. ... 

Scheme 2 shows the results of two studies on the methylation of the lithium enolate of cyclopentanone (10), which was prepared by deprotonation of the ketone with trityllithium in DME or by cleavage of the 1-trimethylsiloxycyclopentene with methyllithium in THF. A signiEcant quantity of over-alkylation occurred when the enolate was treated with methyl iodide, particularly when DME was employed as the solvent at room temperature. Also, as indicated in Scheme 2, Noyori and coworkers showed that by adding 3 equiv. of HMPA to the enolate (10) and reducing the temperature at which the reaction was conducted, the yield of 2-methylcyclopentanone was greatly improved.

In general, the thermodynamically stable extended dienolates (M) have been prepared by deprotonation of enones (62) with sodium or potassium alkoxides in protic solvents or with sodium or potassium hydride in aprotic solvents.Kinetically formed cross-conjugated lithium enolates may be converted into the corresponding extended systems in the presence of excess ketone but in certain cases equilibration is quite slow. Presumably, because the Tr-electron density is higher at the a-carbon than the y-carbon, extended dienolates normally react with alkylating agents to produce a-alkyl-f3,y-unsaturated ketones. 

As shown, Mn-enolates are easily and quantitatively obtained from Li-enolates by transmetalation. b.d.e They can also be prepared by deprotonation of ketones with Mn-amides.4a.c... 

Another general method of enol triflate synthesis is by conversion of a ketone into its enolate ion followed by trapping. For example, the enolate ion prepared by deprotonation of 4-tm-butylcyclohexanone with lithium diisopropylamide (LDA) was trapped by N-phenyltriflimide, but not by triflic anhydride, to give the corresponding enol triflate in 82% yield8,77 (equation 51). 

The most useful method is reaction of ketone (and ester) hthium enolates, usually prepared by deprotonation of ketones with LDA, with either Ce H5 SeBr or Ce Hs SeCl. Enol acetates can be converted into a-phenylseleno ketones by reaction with phenylselenenyl trifluoroacetate, prepared in situ by treatment of CeHsSeCl or CeHsSeBr with silver trifluoroacetate or by conversion to the lithium enolate and reaction with CeHsSeBr. It is sometimes possible to obtain isomeric a-phenylseleno ketones by use of these two methods (equations 1 and II). 

A related enolate complex [Na Pr 2PC(H)=C(0)Ph ]4 has been prepared by deprotonation of the ketone Pr PCH2C(0)Ph with NaN (SiMes)2 170). In the solid state this complex adopts a cubane-type structure with a Na404 core. Each ligand bridges opposite edges of the cube, forming a five-membered chelate ring at each sodium. The Na-P distance in this complex of 2.852(2) A is short in comparison to other similar contacts. 

Enolate alkylation can be difficult to carry out with simple aldehydes and ketones. It is not always possible to limit the reaction to monoalkylation, and aldol condensation competes with alkylation, especially with aldehydes. The formation of regioisomeric alkylation products is an issue with unsymmetrical ketones but can be minimized by selecting reaction conditions that favor either kinetic or thermodynamic control of enolate formation. The kinetic enolate of 2-methylcyclohexanone, for example, was prepared by deprotonation with lithium diisopropylamide then treated with benzyl bromide to give predominantly 2-benzyl-6-methylcyclohexanone,... 

Modified Amine Base. The regioselectivity of ketone deprotonation was improved by the use of lithium t-butyldimethylsilyl-amide as base. The base was prepared by deprotonation of isopropylamine with n-BuLi in THF (eq 22). The resulting anion was quenched with TBDMSCl to give the amine in 70% yield after distillation. Deprotonation of various ketones using this amide base was found to be equally or more selective than LDA. For example, the TBDMS-modified base gave a 62 38 ratio of kinetic to thermodynamic enolate, whereas LDA gave a 34 66 ratio with phenyl acetone. 

C-Silylation. 2-Silyloxazoles can be prepared by deprotonation and quenching the resulting ambident oxazole anion (isocyano enolate) chemoselectively with trialkylsilyl triflates (eq 46). Trialkylsilyl chlorides generally give the product of O-silylation. ... 

Transition Metal-Catalyzed Allylie Alkylation. Chelated amino acid ester enolates were found to be suitable nucleophiles for palladium-catalyzed allylie alkylations (eq 25). They were conveniently prepared by deprotonation of a glycine derivative with LHMDS followed by transmetallation with zinc chloride. The palladium-catalyzed allylie alkylation then takes place in the presence of allyl carbonates to produce the desired anti amino acid derivative. ... 

The nitrogen analogs of enolate ions, referred to as metalloenamineSy can be prepared by deprotonation of imines ... 

---