TMEDA enolates

Several ester enolates have also been examined by X-ray crystallography. The enolates of /-butyl propionate and /-butyl 3-methylpropionate were obtained as TMEDA solvates of enolate dimers. The enolate of methyl 3,3-dimethylbutanoate was obtained as a THF-solvated tetramer. 

Fig. 1.1. Crystal structure of lithium enolate of methyl -butyl ketone in a structure containing four Li+, two enolates, and one HMDA anions, one bromide ion, and two TMEDA ligands. Reproduced from Angew. Chem. Int. Ed. Engl., 35, 1322 (1996), by permission of Wiley-VCH.

In order to gain more insight into this proposed mechanism, Montgomery and co-workers tried to isolate the intermediate metallacycle. This effort has also led to the development of a new [2 + 2 + 2]-reaction.226 It has been found that the presence of bipyridine (bpy) or tetramethylethylenediamine (TMEDA) makes the isolation of the desired metallacycles possible, and these metallacycles are characterized by X-ray analysis (Scheme 56).227 Besides important mechanistic implications for enyne isomerizations or intramolecular [4 + 2]-cycloadditions,228 the TMEDA-stabilized seven-membered nickel enolates 224 have been further trapped in aldol reactions, opening an access to complex polycyclic compounds and notably triquinanes. Thus, up to three rings can be generated in the intramolecular version of the reaction, for example, spirocycle 223 was obtained in 49% yield as a single diastereomer from dialdehyde 222 (Scheme 56).229... 

Alkynyl enals cyclize on treatment with a stoichiometric amount of Ni(COD)2/TMEDA complex to give nickel enolates such as 193,436>436a These metallacycles react with electrophiles including methyl iodide and benzaldehyde to yield cyclopentenol derivatives (Scheme 91). 

Addition of RCu to enones silyt enol ethersThe known ability of ClSi(CH3)3 to facilitate addition of cuprates to enones has been extended to addition of alkylcoppers to enones. Indeed silyl enol ethers can be obtained readily by addition of RCu to enones in the presence of ClSi(CH3)3 and TMEDA. A further advantage is that the RCu can be obtained by reaction of RLi with commercial Cul directly. 

Use of TMSCl in combination with HMPA, DMAP, or TMEDA all favored 1,2-addition over 1,4-addition. Sequential a-alkoxyalkylcuprate conjugate addition, enolate trapping with TMSCl, and silyl enol ether alkylation provides a one-pot synthesis of tetrahydrofurans (Scheme 3.35) [129]. Cyclic enones afford as-fused tetrahydrofurans, while acyclic systems give complex mixtures of diastereomers. a-Alkoxyalkylcopper reagents also participate in allylic substitution reactions with ammonium salts [127]. 

These compounds derived from 3-acetylthiazolidine-2-thione are very versatile chiral materials, capable of being transformed into various synthetic intermediates as previously demonstrated (30). Furthermore, in the stannous enolate mediated aldol-type reactions of 3-(2-benzyloxyacetyl)thiazolidine-2-thione, the stereochemical course of the reaction is dramatically altered by the addition of TMEDA as a ligand. High asymmetric induction is also achieved by the addition of a chiral diamine derived from (S)-proline (31). 

In comparison to other vinylic compounds , the vinyl proton in 1-alkenyl carbamates, deprotonation has a very high kinetic acidity . After protection of the 4-hydroxy group in the homoaldol products by silylation, deprotonation (w-BuLi, TMEDA, diethyl ether or THF) of enol carbamate 384 is complete at —78 °C (equation 103), and the resulting vinyUithium 385 can be kept at this temperature without decomposition for several hours. Stannylation , silylation , methoxycarbonylation (with methyl chloroformate) ... 

Notably, the lithium enolates have the planar methylenecyclopropane-type structure56, but give C-alkylation products49"52. X-ray structure analysis of the lithium enolate56 and bicyclobutyllithium57 TMEDA complexes revealed that both crystallize as lithium bridging dimers. 

In the reaction of allyl acetate 217 with ketene silyl acetal 218 of methyl acetate, using a Pd catalyst coordinated to DPPP, cyclopropane 220 is formed in addition to the expected allylacetate 219 [104], The cyclopropanation becomes main reaction when TMEDA, as a ligand, and thallium acetate are added [105]. The cyclopropanation can be understood by the attack of the enolate ion at the central carbon of 7r-allylpalladium to form the palladacyclobutane 221, followed by reductive elimination. 

The yields from aldehyde alkylidenation is somewhat lower due to the reductive dimerization of aldehydes with low-valent Ti. Alkylidenation of esters is possible by the reaction of 1,1 -dibromoalkane. TiCU and Zn in the presence of TMEDA to give (Z) vinyl ethers [60], Cyclic vinyl ethers are prepared from unsaturated esters in two steps. The first step is formation of the acyclic enol ethers using a stoichiometric amount of the Ti reagent, and the second step is ring-closing alkene metathesis catalysed by Mo complex 19. Thus the benzofiiran moiety of sophora compound I (199, R = H) was synthesized by the carbonyl alkenation of ester in 197 with the Ti reagent prepared in situ, and the subsequent catalytic RCM of the resulting enol ether 198 catalysed by 19 [61]. 

Silyl ketene acetals from esters.1 Ireland has examined various factors in the enolization and silylation of ethyl propionate (1) as a model system. As expected from previous work (6, 276-277), use of LDA (1 equiv.) in THF at —78 -+ 25° results mainly in (E)-2, formed from the (Z)-enolate. The stereoselectivity is markedly affected by the solvent. Addition of TMEDA results in a 60 40 ratio of (Z)- and (E)-2 and lowers the yield significantly. Use of THF/23% HMPA provides (Z)- and (E)-2 in the ratio of 85 15 with no decrease in yield. This system has been widely used for (E)-selective lithium enolate formation from esters and ketones. Highest stereoselectivity is observed by addition of DMPU, recently introduced as a noncar-... 

Equation 76) <1993OM3019>, which react as ester and ketone enolate equivalents, respectively. The latter reaction requires the use of fluoride ion activation (tetrabutylammonium fluoride, TBAF) to actuate the addition. Central carbon alkylation is less common for allylpalladium reactions despite this, nucleophilic alkylation of TMEDA-stabilized 1,3-diphenylallyl palladium complexes proceeds selectively to the central carbon (Equation 77) <1995AGE100>. 

Figure 13.2 shows structures that contain two lithium enolates each. But again, these structures are not pure dimers. Both lithium atoms employ two of their coordination sites to bind to an N atom of the bidentate ligand TMEDA (see Figure 13.2 for name and structure). 

Fig. 13.2. X-ray single crystal structures of lithium enolates. TMEDA, tetramethylethylenedi-amine.

The synthesis of complex polycyclic molecules has been achieved by Montgomery et al. by cascade cyclization processes involving nickel enolates [40]. Up to three cycles could be generated in the intramolecular version of the reaction. Alkynyl enal or enone were first converted into their corresponding seven-membered cyclic enolates in the presence of Ni(cod)2/TMEDA [41 ]. These species could be trapped by electrophiles such as aldehydes. For example, upon treatment with the nickel catalyst, dialdehyde 32 afforded spiro-cycle 35 in 49% yield as a single diastereomer (Scheme 17). 

Allenyl trialkylsilyl ethers 771 can be a-deprotonated with f-BuLi in THF at — 78 °C to give the allenyllithiums 77210901091. They underwent reverse Brook rearrangement to afford the silaacrolein enolates 773, which react with aldehydes and ketones to yield the a,/9-unsaturated acyl silanes 774 (Scheme 200). For enolizable aldehydes transmetallation with ZnCl2-TMEDA, and MgBr2 for ketones, provided better yields. 

The structure of mixed aggregates involving ester enolates is also of major interest to macromolecular chemists, since ionic additives are often introduced in the polymerization medium. The more stable arrangement between lithium 2-methoxyethoxide and MIB lithium enolate was thus calculated (at the DFT level) to be a 5 1 hexagonal complex with similar O—Li lateral coordinations212. The same team has recently extended this study to complexes formed between the same enolate in THF and a-ligands such as TMEDA, DME, 12-crown-4 and cryptand-2,1,1213. Only in the case of the latter ligand could a separate ion pair [(MIB-Li-MIB),2 THF]-, Li(2,l,l)+ be found as stable, still at the DFT level, as the THF solvated dimer [(MIB-Li)2,4 THF]. 

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