Crystal lithium aldolate

The successive replacement of the enolate by aldolate moieties en route from an enolate tetramer to an aldolate tetramer might involve severe reconstruction of the skeleton. Thus, a mixture of pinacolone, its lithium aldolate with pivalaldehyde, and the enolized aldolate dianion was recently reported to cocrystallize in a 1 1 3 ratio as a heptalithium cage compound missing any cube-shaped unit [15]. Rather complex crystal structures aldolate-enolate aggregates were also found for calcium enolates [8b]. 

The Michael reaction with enamines is exemplified in this procedure. In a second (spontaneous) step of the reaction, an aldol-type condensation occurs resulting in cyclization. Finally, the morpholine enamine of the product forms and is hydrolized by the addition of water to yield a mixture of octalones, which is separated by fractional crystallization. J -Octalone-2 can be reduced by lithium in anhydrous ammonia to the saturated tra/i5-2-decalone (Chapter 3, Section III). 

More recently, Enders group has described the X-ray crystal structure of the chiral hydrazone anion (19). This internally chelated chiral hydrazone crystallizes as the bis(tetrahydrofuran) monomeric adduct. The lithium in this structure is 17° out of the C—C— N plane and is predominantly associated with the anionic nitrogen (and the chelating methoxy group). Interactions with the =CH2 carbon are minimal. Earlier studies by Bauer and Seebach had examined the association behavior of (19). They found that in THF this azaallyllithium reagent was monomeric. While there is no or ri -interaction with the azaallyl anion, the lithium in this structure is tetracoordinate and prochiral. Preferential coordination of lithium to an electrophile such as a carbonyl oxygen with selective replacement of one THF moiety could be involved in some of the asymmetric aldol reactions discussed below. 

Asymmetric aldol reactions. The chiral N-propionyloxazolidinone (1), prepared in several steps from (lR)-(—)-camphorquinone, undergoes highly diastereoselective aldol reactions with the additional advantage of high crystallinity for improving the optical purities of crude aldols. Either the lithium enolate or the titanium enolate, prepared by transmetalation with ClTi(0-(-Pr)3, reacts with aldehydes to form syn-adducts with diastereomeric purities of 98-99% after one crystallization. The observed facial selectivity is consistent with metal chelation of intermediate (Z)-enolates (supported by an X-ray crystal structure of the trapped silyl enol ether). The lithium enolate also exhibits... 

Another early solution to the acetate aldol problem came from the so-called Davies-Liebeskind enolates already mentioned in the context of enolate alkylation. As elaborated independently by the groups of Davies [138] and Liebeskind [139], the deprotonation of the chiral acetyl iron complex 124b, transmetallation of the lithium enolate, and addition to aldehydes lead to the predominant formation of diastereomers 279, as proved by a crystal structure analysis. The diastereoselectivity strongly depends on the transmetallation, the best results being obtained with diethylaluminum chloride. With other additives, the topicity is reversed, and the diastereomer 280 is obtained as the major product. The decomplexation of the adducts leads to P-hydroxycarboxylic acids (Scheme 4.64). 

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