Amide lithium enolate structure

Detailed investigations indicate that the enolization process (LDA, THF) affords enolates 37 and 38 with at/east 97% (Z)-stereoselection. Related observations have recently been reported on the stereoselective enolization of dialkylthioamides (38). In this latter study, the Ireland-Claisen strategy (34) was employed to assign enolate geometry. Table 10 summarizes the enolization stereo selection that has been observed for both esters and amides with LDA. Complementary kinetic enolization ratios for ketonic substrates are included in Table 7. Recent studies on the role of base structure and solvent are now beginning to appear in the literature (39,40), and the Ireland enolization model for lithium amide bases has been widely accepted, A tabular survey of the influence of the ester moiety (ORj) on a range of aldol condensations via the lithium enolates is provided in Table 11 (eq. [24]). Enolate ratios for some of the condensations illustrated may be found in Table 10. It is apparent from these data that ( )-enolates derived from alkyl propionates (Rj = CH3, t-C4H9) exhibit low aldol stereoselectivity. In contrast, the enolates derived from alkoxyalkyl esters (Rj = CHjOR ) exhibit 10 1 threo diastereo-... 

Be this as it may, lithium attempts to bind to several bonding partners the structural consequences for the enolates of a ketone, an ester, and an amide are shown in Figure 13.2 In contrast to the usual notation, these enolates are not monomers at all The heteroatom that carries the negative charge in the enolate resonance form is an excellent bonding partner such that several of these heteroatoms are connected to every lithium atom. Lithium enolates often result in tetramers if they are crystallized in the absence of other lithium salts and in the absence of other suitable neutral donors. The lithium enolate of fert-butyl methyl ketone, for example, crystallizes from THF in the form shown in Figure 13.3. 

This volume, which complements the earlier one, contains 9 chapters written by experts from 7 countries. These include a chapter on the dynamic behavior of organolithium compounds, written by one of the pioneers in the field, and a specific chapter on the structure and dynamics of chiral lithium amides in particular. The use of such amides in asymmetric synthesis is covered in another chapter, and other synthetic aspects are covered in chapters on acyllithium derivatives, on the carbolithiation reaction and on organolithi-ums as synthetic intermediates for tandem reactions. Other topics include the chemistry of ketone dilithio compounds, the chemistry of lithium enolates and homoenolates, and polycyclic and fullerene lithium carbanions. 

Generally, ester enolates of structure (202 R = M, R = Oalkyl) rearrange via a 3,3-shift, whereas the corresponding amide enolates (202 R = M, R = N(alkyl)2) and acid dianions (202 R = M, R = OM) prefer the 2,3-pathway (equation 20). Both pathways have been observed with ketone enolates (202 R = M, R = alkyl). With substrate (179), Koreeda and Luengo observed only traces of Wittig rearrangement product (205), except for the lithium enolate, where (205) accounted for up to 20% of the reaction mixture (equation 21). ° Thomas and Dubini, however, reported predominant formation of 2,3 Wittig products (207) and (209) under base treatment of ketones (206) and (208) (equation 22). ... 

The least highly substituted amide enolate whose structure is known is the lithium enolate of N -di-methylpropionamide (170). This enolate is obtained as a dimer solvated by TriMEDA, i.e. (171). The alkene geometry in (171) is opposite that found in the ester enolates from (163) and (165). Thus in the... 

Scheme 5.29. Proposed chelated transition structures (and topicities) for Michael additions of lithium enolates of ketones, esters, and amides to enones [157,158]. Only one enantiomeric transition structure and product is shown for each topicity (Si face of the acceptor).

As indicated by Entry 5 in Table 6.2, the lithium enolates of pyrrolidine amides show excellent simple diastereoselectivity, and rearrange in excellent yields [69]. These amides also show a slight dependence of selectivity on the structure of the amide base used [69]. Monosubstituted pyrrolidine amides were poor auxiliaries for this reaction (<76% ds) [69], but C2-symmetric pyrrolidines are highly selective, as shown in Scheme 6.22 [90]. The Si facial selectivity of the lithium enolate and the illustrated zirconium enolate were comparable, but only the zirconium enolate also showed a high preference for the ul topicity illustrated. The two views of the transition structure rationalize both the topicity and the absolute configuration of the product. The enolate Si face is favored because the closer of the two pyrrolidine stereocenters blocks the Re face. The ul topicity is favored because when the enolate moiety is on the concave face of the cyclopentane envelope, a severe interaction between a pseudoaxial hydrogen and a cyclopentadiene is avoided cf. Scheme 6.14 a for another illustration). 

Similarly, selectivity was observed in Weinreb s efforts toward the synthesis of the microbial immunosuppressive agent FR901483.24 In this case, axial addition was favored by reaction of the lithium enolate of amide 35 with racemic 1 to produce 36. An interesting reversal of stereoselectivity was observed when, on slight alteration of the synthetic sequence, the Boc-protected amide was subjected to similar conditions. For reasons not fully understood, equatorial alcohol 37 was produced in a 53% yield, the structure of which was confirmed by X-ray crystal analysis. 

Lithium enolates of ketones exist as aggregates in solution.29-3l,34d,35 Mixed aggregates between the enolate anion and the amide base are also possible. In 1981, Seebach and co-workers confirmed by X-ray crystallography that the lithium enolates of pinacolone and cyclopentanone form a tetrameric aggregate in the solid state, and it was assumed that a similar species exited in solution. A THF solvated tetramer of lithium pinacolonate is shown (see 33), as it was reported by Seebach. Williard et al. reported the X-ray structure of... 

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