Structure amide enolates

The 1,4-conjugate addition of ester enolates to a, 3-enones was first reported by Kohler in 1910,138a c as an anomalous Reformatsky reaction, but chemoselectivity was dependent on the structure of the a,(3-enone and restricted to bromozinc enolates obtained from either a-bromoisobutyrate or bromomalonate esters (Scheme 66).138d,e Further evaluation, with lithio ester enolates and lithio amide enolate additions, has resulted in identification of four factors that affect the chemoselectivity and diastereoselectivity of additions to a, 3-enones.139 These factors are (a) enolate geometry, (b) acceptor geometry, (c) steric bulk of the -substituent on the acceptor enone and (d) reaction conditions. In general, under kinetic reaction conditions (-78 °C), ( )-ester enolates afford preferential 1,2-addition products while (Z)-ester enolates afford substantial amounts of 1,4-addition products however, 1,2 to 1,4 equilibration occurs at 25 C in the presence of HMPA. The stereostructure of the 1,4-adducts is dependent on the initial enolate structure for example, with ( )-enones, (Z)-ester enolates afford anti adducts, while (E)-ester enolates afford syn adducts (Scheme 54). In contrast, amide enolates show a modest preference for anti diastereomer formation. 

The intramolecular Heck reaction is a powerful method for the synthesis of constrained tertiary and quaternary carbon centers and has been applied as a key step in the synthesis of a number of pyridine alkaloids. Mann et al. have accessed the bicyclononane core structure of huperzine A 150 in moderate yield by intramolecular Heck reaction of bromopyridine 151 (Equation 117). Another notable application of this methodology is the intramolecular a-arylation of the amide enolate generated from 152 to give the carbon skeleton of cytosine <20040BC1825> (Equation 118). 

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... 

A recent report on the first structurally characterized organozinc amide enolate has appeared, and the observations are consistent with ours. Hlavinka, M.L. Hagadom, J.R. Organometallics 2005,24,4116. Although drawn as monovalent in Equation 20.2 for clarity, it is assumed that lithium is tetracoordinate, and 12-crown-4 is displacing other hgands hound to lithium, such as THE. 

For amide enolates, the situation is similar in that, when R3 and Y are large, the transition structures of paths a and c are favored [158]. However, recall that acyclic amides invariably form Z(0j-enolates, so amide COj-enolates are only possible when R2 and Y are joined i.e., in a lactam. In contrast to ketone and ester enolates, however, the transition structures of paths b and d appear to be intrinsically favored when Y and R3 are small. This latter trend is (at least partly) contrary to what would be expected based on the simple analysis of Figure 5.9, but can be rationalized as follows. For the lactams, the R2 and Y substituents present a rather flat profile, so that interaction with R3 in path d is minimal. Additionally, the R2-Y ring eclipses the P-hydrogen of the enone in c, destabilizing this structure. For amide Z(0)-enolates and acceptors with an R3 substituent such as a phenyl, there may actually be an attractive interaction between Y and R3, favoring path b. 

These four examples do not seem to comply with a consistent mechanistic model. The dilithioprolinol amide enolate in Scheme 5.31a is attacked on the enolate Si face, in accord with the sense of asymmetric induction observed in alkylations of this enolate [166,167]. On the other hand, the structurally similar dilithiovalinol amide enolate, while being attacked on the same face (as expected), reverses top-icity. Furthermore, the S,S-pyrrolidine enolate in Scheme 5.31c is attacked from the Si face by Michael acceptors, but from the Re face by alkyl halides [168] and acid chlorides [169]. The titanium imide enolate in Scheme 5.31d adds Michael acceptors from the Si face, consistent with the precedent of aldol additions of titanium enolates (c/. Table 5.4, entry 2, [88]). An intramolecular addition (Scheme 5.3le) seems to follow a clear mechanistic path [165] the Si face is attacked by the electrophile, and the cis geometry of the product implicates intramolecular complexation of the acceptor carbonyl. This coordination of the acceptor carbonyl is probably a function of the metal recall the lithium ester enolates illustrated in Scheme 5.30c and d, but also metal chelation in titanium aldol additions (Table 5.4, entry 2). 

Scheme 6.14. Possible transition structures for the [2,3]-Wittig rearrangement of the R-allylic ester enolates shown in Scheme 6.13. For amide enolates, see Scheme 6.22.

The work of Myers et al. [6] illustrates the synthetic potential of the use of metal salts (instead of HMPA ) in alkylation reactions of enolates, employing easily accessible amide, enolates of the chiral auxiliary pseudoephed-rine. It is not surprising that the mechanism of chiral induction is not yet fully understood further investigations are necessary. Nonetheless, unanswered questions in enolate chemistry remain even for tailor-made, well-established auxiliaries, whose asymmetric induction can be explained convincingly by working models on monomer enolate structures, considering chelation control and steric factors. 

It was suggested on the basis of theoretical calculations that the transient intermediates with infrared bands at 1676—1680 cm observed for reaction of substituted phenylketenes with diethylamine in acetonitrile were amide enols rather than the zwitterions. Rate constants for conversion of the amide enol intermediates to the amides were interpreted as showing significant delocalization of negative charge into the aromatic Tt-system in the j8-phenylenolate structure formed by proton removal. ... 

Cp2Zr(Me)Cl, respectively. Their NMR spectra clearly reveal that the O-bond character of the enolate, indicated by the carbon-carbon double bond, is maintained in solution (Scheme 3.8) [53]. Crystal structures were also obtained for O-bound zirconium acetophenone enolate 21 [55], titanium ketone enolate 22, derived from/) r -methylacetophenone, and amide enolate 23 [56]. Whereas the latter readily added to benzaldehyde, the ketone enolate 22 (X = Ph) failed to undergo an aldol addition. This difference in reactivity was explained - based on a computational study - by a higher electron density at the methylene carbon atom in the amide compared to the ketone enolate [56]. 

UV spectra of a variety of 1 -alkyl-1 //-1-benzazepines,20,21 3//-l-benzazepines,20 l-acyl-l//-l-benzazepines,1 3,22,23 3-acyl-3//-3-benzazepines,22-23 3-alkyl-37/-3-benzazepines and their cations in concentrated sulfuric acid,24,25 and 3-mesyl-3//-3-bcnzazepine,2ft have been recorded. A comparison of the UV spectra of 3-alkyl-l, 5-dihydroxy-3//-3-benzazepinc-2,4-dicarboxylates and their bis-O-methyl ethers supports an enol rather than an amide structure for these derivatives.14... 

Show how resonance can occur in the following organic ions (a) acetate ion, CH,CO, (b) enolate ion, CH,COCH5, which has one resonance structure with a C=C double bond and an —O group on the central carbon atom (c) allyl cation, CH,CHCH,+ (d) amidate ion, CH,CONH (the O and the N atoms are both bonded to the second C atom). 

Similar effects were observed in the structures of the lithium salts of ester enolates [43] studied by Seebach et al. (1985). Here too systematic differences in angles are observed compared with amide and ketone enolates, and there is a correlation between the bond angles and the difference in the two C-O bond lengths at the reaction centre for three compounds [43], consistent with incipient elimination of t-butoxide to give the ketene [44] (Ferretti et al., 1991). 

Schulenberg (117) describes the material 55a, which is obtained from the amide 55c on reaction with a deficiency of sodium methoxide the white prisms of the product melt at 110 to 122°C (variable). These crystals give fairly stable solutions, enabling measurement of the NMR spectrum and observation that the material gives a positive FeCl3 reaction, in accord with the enol structure. After recrystallization a mixture of crystals of 55a and pale yellow prisms melting at... 

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