Magnesium ester enolates

The addition of lithium or magnesium ester enolates to nitrones in THF at 78°C or in Et20 at — 20°C, constitutes a direct synthesis of /V-hydroxy- 3-amino acid esters (Scheme 2.180) (645). 

C. Reactions of Magnesium Ester Enolates and Magnesium Lactone Enolates with Electrophiles... 

It is useful to note that Hiyama and Kobayashi have reported successful reactions of nitriles with a magnesium ester enolate (Scheme 23), whereas the corresponding lithium ester enolate failed to react. 

VinylpyridineS. The stereochemistry of anionic polymerization of 2-vinylpyridine is predominantly isotactic for most polymerization conditions as shown by the data in Table 14 (166). The coordination of the penultimate psrridyl nitrogen with the magnesium ester enolate at the chain end has been invoked to... 

Acyl imidazolides are more reactive than esters but not as reactive as acyl halides. Entry 7 is an example of formation of a (3-ketoesters by reaction of magnesium enolate monoalkyl malonate ester by an imidazolide. Acyl imidazolides also are used for acylation of ester enolates and nitromethane anion, as illustrated by Entries 8, 9, and 10. (V-Methoxy-lV-methylamides are also useful for acylation of ester enolates. 

Asymmetric synthesis in aldol-type reaction involving magnesium ester or lactone enolates has also been reported. Enolate of (—)-menthyl or (-l-)-bornyl acetate reacts with substituted benzophenones or a-naphtophenones to yield, upon hydrolysis of the resulting esters, optically active /3-hydroxyacids. Although these results are interpreted in terms of a steric factor. Prelog s rules are not applicable to these reactions (equation 88). 

A reaction similar to the above involves the acylation of malonic ester through its magnesium enolate. Thus, the reaction of propionyl chloride with the ester enolate leads to diethyl propionylmalonate. Thermal decomposition of this compound with /3-naphthalenesulfonic acid yields ethyl propionylacetate (57%). This modification appears to be general in that it has been extended to the use of aliphatic, aromatic, and car-balkoxy acyl chlorides. ... 

Aldol-Type Addition. Aldol-type addition of the magnesium enolate of (R)-(+)-7-butyl 2-(p-tolylsulfinyl)acetate, prepared with 7-butylmagnesium bromide, with aldehydes and ketones afforded, after desulfurization with Aluminum Amalgam, p-hydroxy esters in very high diastereoselectivity (eq Two chiral centers are created in the first step with very high diastereoselectivity (mainly one diastereomer is formed). A model M based on the structure of the sulfinyl ester enolate (determined by C NMR) and on electrophilic assistance of magnesium to the carbonyl approach, was proposed to explain and predict the absolute configuration of the two created chiral centers. ... 

A series of Grignard reagents were reacted with aliphatic esters, and enolization occurred selectively at the less-hindered position. Interestingly, the ester enolate eliminates magnesium alkoxide, forming a ketene intermediate that reacts with a second equivalent of Grignard reagent to form keto-enolates [17 Eq. (13)]. 

The condensation reaction of ester enolates with nitriles are an important general source of alkenyl-P-amino acids. In a simple example, the reaction of t-bulyl acetate with magnesium diisopropylamide and then propanenitrile led to /-butyl 3-amino-hex-2-enoate, 4.81. In addition, /-butyl 3-aminobut-2-enoate (66%), 3-amino-4-methylpent-2-enoate (74%), 3-amino-4,4-dimethylpent-2-enoate (43%), 3-amino-4-phenyIpent-2-enoate (25%) and other 4-aryl and 2-alkyl- ubstituted alkenylamino... 

At a glance, the descriptors Z and E might seem to be appropriate for O - metal-bound enolates like 6. Indeed, E/Z nomenclature causes no problems when the configuration of preformed enolates derived from aldehydes, ketones, and amides has to be assigned, because the O-metal residue at the enolate double bond has the higher priority. However, application of the E/Z descriptors to ester enolates leads to the dilemma that enolates with different metals but otherwise identical structures will be classified by opposite descriptors, as illustrated by lithium and magnesium enolates 9 and 10, respectively the former would have to be termed Z, and the latter E (Scheme 1.4). 

The big difference between the extent of asymmetric induction on the addition to a prostereogenic carbonyl group of simple carbanions a to a chiral sulfoxide on the one hand and enolates of sulfinyl esters on the other, can be attributed to the capacity of the ester function to chelate magnesium in the transition states and intermediates. The results already described for the addition of chiral thioacetal monosulfoxide to aldehydes (see Section 1.3.6.5.) underscore the importance of other functions, e.g., sulfide, for the extent of asymmetric induction. 

Tin(Il) shows considerable affinity towards nitrogen, therefore is expected to activate the imino group. The diastereoselective addition of tin(II) enolates derived from thioesters 1 to x-imino-esters 2 is reported12. This reaction proceeds smoothly to afford. vi w-/j-amino acid derivatives 3 (d.r. 95 5) in good yields. Lithium, magnesium, and zinc enolates do not react while titanium enolates give the adducts in low yield with preferential formation of the anti-isomer. 

The enolate geometry can be controlled, in the case of esters, by the addition of HMPA without HMPA the enolate has predominantly the. E-geometry, while with HMPA mainly Z-geometry is observed. Similar additions with magnesium and zinc enolates are observed24"32 373 374. 

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