Reversibility enolate geometry

In isolated cases diastereoselectivity is reversed 2S>. Either acyclic transition states are transversed, or the usual pericycles are involved, having chair or boat conformations depending upon the enolate geometry, the substituents and the nature of the aldehyde 25>. These possibilities have also been discussed in irregularities reported for other enolates 48 109-m). For example, dicyclopentadienylchlorozirconium-109>, triphenyltin u0> and tris(dialkylamino)-sulfoniumnl> (TAS) enolates also favor... 

Hydrogen transfer represents a non-reversible reaction with a quantum yield dose to 100%, i.e., there is no return to the enol geometry after the fast formation of the keto product. Calculations of wavepacket propagation in the Sj state, assuming harmonic potentials for the modes contributing to... 

While more plentiful, alcohol-based chiral auxiliaries have been limited in their ability to direct the diastereoselective hydroxylation for the preparation of tertiary a-hydroxy acids. Among these, the best results in this series were obtained when oxidation of the enolate of chiral ester substrate 24 with (+)-5 yielded (5)-25.ub The use of (-)-S as the hydroxylating agent, provided a reversal in stereoselectivity, providing (i )-25. Interestingly, when substoichiometric amounts (0.5 equiv) of (+)-5 were used, stereoselectivity improves (94% de), a fact attributed to the matching of the enolate geometry to the oxidant. This speculation is credible, as evidenced by the fact that oxidation with 0.50 equivalent of (-)-5 produces (5)-25 in only 37% de in a stereochemically mismatched case. 

Thus, a reversal of the diastereoseleetivity of the reaetion was observed if the enolate was prepared in the presenee of a lithiated base. The different behaviour of the base could be attributable to the geometry of the enolate. It was assumed that the use of KOH as a base would give predominantly the E enolate, whereas the Z enolate would be formed with a lithiated base such as LiN(TMS)2- This methodology was applied to the asymmetric synthesis of quaternary a-amino acids starting from an imino alaninate compound. 

The use of a heteroatom a to the ester carbonyl group allows for the formation of a chelate with the metal counterion hence, the geometry of the ester enolate can be assured.336-338358359 This approach was used in the rearrangement of the glycine allylic esters 13 to y,8-unsaturated amino acids in good yields and excellent diastereoselectivity (Scheme 26.13).358 The enantioselectivity could be reversed by using quinidine instead of quinine. 

The aldol reaction is often used to make enones by dehydration of the aldol itself, a reaction which often occurs under equilibrating aldol conditions, but has to be induced in a separate step when lithium enolates or silyl enol ethers are used. In general one has to accept whatever enone geometry results from the dehydration, and this is usually controlled by thermodynamics, particularly if enone formation is reversible. Simple enones such as 46 normally form as the E isomer but the Z isomer is difficult to prepare. When the double bond is exo to a ring, e.g. 47, the E isomer is again favoured, but other trisubstituted double bonds have less certain configurations. 

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). 

As Scheme 7 shows, our results seem to indicate that the preferred attack by base is off line, pushing the electrons of the C-H bond not simply towards the carbon but towards the carbon and in a direction required by the developing p orbital that is, in a direction towards the carbonyl group. This can also be visualized by considering the reverse reaction, ketonization of the enol. By microscopic reversibility, ketonization must follow the enolization pafliway but in the reverse direction. As Scheme 8 shows, we propose that the BH+ puts the proton on the enol at the side of the carbon p orbital, so the proton will end up in its final position in the re-formed methyl group. If the p orbital electrons displace the B from BH+ by an in-line displacement, as they should, then the geometry is as we have deduced. This is a reasonable geometry for proton removal in the course of enolization (or its reverse) W is the first evidence for it. 

Diastereomeric phosphoramides have been employed to catalyse the asymmetric aldol addition of trichlorosilyl enolates to benzaldehyde. Good anti/syn product ratios were achieved, but these were reversed on employing a more hindered catalyst, and the ratios were also affected by the catalyst concentration. A mechanistic switchover is proposed one transition-state geometry involves a 1 1 complex (cat-alyst enolate) favoured by a hindered catalyst in low concentration, while the other route involves a 2 1 stoichiometry. 

Base-catalyzed methylation of the ketal-ketone (29) gave preponderantly the 5j3-methyl product (30), whereas in the enol ether ketone (31) derived from (29) by pyrolysis the change in molecular geometry caused by the presence of the 2,3-double bond reversed the steric course of the alkylation to lead primarily to the 5a-methyl pruduct, (32) [122]. 

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