Enolates tetramethylethylenediamine

Stereodivergent aldol addition is also possible when (.S,)-5,5-dimethyl-4-trimethylsiloxy-3-hexanonc (16) is chosen as the enolate precursor. Thus, the lithium enolate generated from 16 by treatment with lithium diisopropylamide and tetramethylethylenediamine leads predomi-... 

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... 

The partial reduction of the triple bond of lithium ynoiates 173 by activated LiH provides the lithium ii-enolates 174 derived from aldehydes (equation 70) °. This is a useful reaction, since these enoiates of aldehydes are not easily prepared by the usual base treatment of aldehydes. Activated LiH is prepared in situ from cyclohexa-1,3-diene and lithium tetramethylpiperazide or from cyclohexa-1,3-diene and BuLi. The superactive LiH, prepared from hydrogen with BuLi-tetramethylethylenediamine, can also be used. ... 

In an extension of this methodology, it has been demonstrated that in some cases the enantioselective alkylation of lithium enolates can be achieved by means of a catalytic amount of 1. As in the stoichiometric version (vide supra), the reaction conditions play a crucial role in determining the yield and % ee. One fundamental modification in the catalytic version is the addition of two equiv of an achiral bidentate amine [e.g. tetramethylethylenediamine (TMEDA) or Al,lV,7V, A -tetramethy-Ipropylene diamine (TMPDA)] to trap the large excess of lithium bromide present at the beginning of the reaction. This catalytic asymmetric variant is illustrated by the reaction of the lithium enolate of 1-tetralone with a variety of electrophiles (eq 7). In this example, the optimal reaction conditions were determined to be 0.05 equiv of 1,2.0 equiv of TMPDA, and 10.0 equiv of the alkyl halide. 

Here again, the reaction involved an intramolecular displacement of the iodide by an ester enolate (Scheme 10). Preparation of stable azapalladacycle ( )-93 commenced with treatment of sulfonamide 90, accessible via A -alkylation of A -trifluoromethanesulfonyl-2-iodoaniline with palladium(O) (Pd2(DBA)3 DBA = dibenzylideneacetone) and tetramethylethylenediamine (TMEDA) to afford palladium(ll) complex 91. An easy ring closure of complex 91 provided palladacycle ( )-92 in 92% yield via addition of /-BuOK (IM in solution in THE, 1.2equiv) at room temperature. Displacement of tetramethylethylenediamine with triphenyl-phosphine delivered palladacycle ( )-93 in quantitative yield. 

Protection or reductive deoxygenation of alcohols and ketones. Ireland et al.2 have found that N,N,N, N -tetramethylphosphoroiiamidates (TMPDA derivatives) of alcohols and of ketone enolates are reduced in high yield by lithium-ethylamine. They are readily prepared by phosphorylation of alcoholate or enolate anions. The complete sequence is as follows. The alcoholate anion is simply prepared by treatment of an alcohol with a slight molar excess of n-butyllitliium. The enolate anions of saturated ketones are prepared by treatment with lithium diisopropylamide. In the case of a,/J-unsaturated ketones, lithium-ammonia reduction or conjugate organometallic addition is suitable. For phosphorylation of the Jnion a fivefold excess of N,N,N, N -tetramethyldiamidophosphorochloridate in 4 ] dimethoxyethane (or THF)-N,N,-N. N -tetramethylethylenediamine (TMEDA) is used. The reaction is complete after... 

After this chapter had been completed, there appeared a paper describing the first determination of the thermochemistry of an aldol reaction of a preformed enolate (E. M. Arnett, F. J. Fisher, M. A. Nichols and A. A. Ribeiro, J. Am. Chem. Soc., 1989, 111, 748). The enthalpy of reaction of the hexameric lithium enolate of pinacolone with pivalaldehyde in hexane at 25 C is -30.19 0.76 kcal mol. With one equivalent of various added ligands, enthalpies of reaction are -17.94 0.36 kcal mol in tetrahydrofu-ran (THF) -20.85 0.72 kcal mol in tetramethylethylenediamine (TMEDA) and -19.05 0.44 kcal mol in dimethoxyethane (DME). The product is believed to be a tetrameric lithium aldolate in each case. In view of the discussion given in this section, these reactions are surprisingly exothermic. Note, however, that one equivalent of THF makes the reaction about 10 kcal mol less exothermic. The enthalpy of reaction in pure THF has yet to be determined experimentally. 

Interestingly, CO has a positive effect on the yield of the reaction, although it is not incorporated [112]. It is observed, that the combination TMEDA/CO (tetramethylethylenediamine) is superior to HMPA/NEtj under the same reaction conditions. Under these modified conditions, not only sterically hindered ester enolates, but also deprotonated amides, lactams, ketones, sulfones, and the Evans enolates can be transformed [113]. Tertiary anions give the best results. 

The tin(II) enolate prepared from (1), tin(II) trifluoromethane-sulfonate, and 1-ethylpiperidine reacts with aldehydes in the presence of A(, fY,fV -tetramethylethylenediamine (TMEDA) to afford the anti aldol adducts in good yields with good selectivities (eq 1). Interestingly, syn selective reactions proceed in the absence of TMEDA. Optically active antf aldol adducts can be obtained in the presence of chiral diamine (2) instead of TMEDA. 

Deoxo-l,2-dihydro-6-episantonin treated at 5° with excess triphenylmethyl-lithium in dimethoxyethane in the presence of tetramethylethylenediamine, and the resulting enolate quendied with 1,2-dibromoethane at the same temp. -> a-bromolactone (Y ca. 50%) refluxed 1 hr. with excess diazabicyclononene in toluene (-)-frullanolide (Y 80%). F. e. s. A. E. Greene, J.-C. Muller, and G. Ourisson, Tetrah. Let. 1972, 2489 f. method, also endocyclic a,j -ethylene-y-lactones, cf. ibid. 1972, 3375. 

The lithium enolate of t-amyl acetate exists as a doubly chelated dimer in the presence of TMEDA (A,A,A, At -tetramethylethylenediamine). Reaction with a simple aldimine such as pflra-F-C6H4-CH=N-Ph gives an iV-lithiated -amino ester as a monomer, observed by Li- and i N-NMR. Kinetic studies by i F-NMR give a reaction order consistent with a TS of stoichiometry [(ROLi)2(TMEDA)2(imine)], supported by DPT calculations. That such aza-aldol condensations involve dimeric mechanistic routes runs counter to many claims that monomers are more reactive. 

Ketones such as acetone and cyclohexanone have been converted into their a,a -dianions by treatment of the corresponding potassium enolates with n-butyl-lithium and tetramethylethylenediamine [equation (42)]. Such dianions are strongly nucleophilic towards alkyl halides and carbonyl compounds. Dialkylation is not a significant side reaction owing to the great difference in reactivity between the dianion and the enolate. 

The use of hexamethylphosphoric triamide and triethylamine as ligands in place of the usual phosphines in the addition of ester enolates to 1 results in the formation of cyclopropanes via the unusual initial attack at the central carhon atom (eq 6). The process is very limited with respect to nucleophile, however, as only branched ester enolates produce a cyclopropane. N,NJ 1, N -tetramethylethylenediamine and carbon monoxide as hgands also promote central carbon attack by ester enolates. ... 

Sometimes enolate reactivity can be enhanced by adding a reagent to the medium which can bind alkali metal cations strongly by chelation. One popular choice for this purpose is tetramethylethylenediamine (TMEDA), which... 

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