Ester enolates acyclic

The use of nonstabilized carbon nucleophiles in this reaction has been rare. Recently, however, it was shown that lithium ester enolates participate in Pd-cata-lyzed 1,4-additions to cyclic and acyclic vinyloxiranes, affording the corresponding 6-hydroxy-4-enoates in good yields and with complete regioselectivity [117, 118]. 

The geometry of the ester enolate dictates the configuration of the cxtracyclic asymmetric center an (ii)-enolate gives mainly an anti-adduct and a (Z)-cnolate gives a wn-adduct. This is in accordance with the stereochemical results with tram-acyclic esters bearing in mind the fact that in this case a cw-unsaturated ester is present in the cyclic Michael acceptor. 

Davis et al.111 developed another method for reagent-controlled asymmetric oxidation of enolates to a-hydroxy carbonyl compounds using (+)-camphor-sulfonyl oxaziridine (147) as the oxidant. This method afforded synthetically useful ee (60-95%) for most carbonyl compounds such as acyclic keto esters, amides, and a-oxo ester enolates (Table 4-20). 

Jorgensen s group44a carried out the reaction using the anhydrous form of chiral bis(oxazoline) coordinated copper complex. Complex 106 containing 83 as the chiral ligand was found to be the most effective. As shown in Scheme 5-32, the asymmetric hetero Diels-Alder reaction of //.y-unsaturated a-keto esters with acyclic enol ethers results in products with excellent yield and enantioselectivity. 

Diastereoselectivity in the aldol and the conjugate additions of 2 -hydroxy-1,T-binaphthyl ester enolates with a variety of carbonyl electrophiles has also been explored the tendency of the ester enolates, generated by BuLi, to react with aldehydes to give threo products preferentially with high diastereoselectivity has been interpreted in terms of an acyclic transition state of chelated lithium enolate involving the aldehyde carbonyl and the 2 -hydroxy group. 

Enantioselective condensation of aldehydes and enol silyl ethers is promoted by addition of chiral Lewis acids. Through coordination of aldehyde oxygen to the Lewis acids containing an Al, Eu, or Rh atom (286), the prochiral substrates are endowed with high electrophilicity and chiral environments. Although the optical yields in the early works remained poor to moderate, the use of a chiral (acyloxy)borane complex as catalyst allowed the erythro-selective condensation with high enan-tioselectivity (Scheme 119) (287). This aldol-type reaction may proceed via an extended acyclic transition state rather than a six-membered pericyclic structure (288). Not only ketone enolates but ester enolates... 

Among several chiral cyclic and acyclic diamines, (R,R)-cyclohexane-l,2-diamine-derived salen ligand (which can adopt the gauche conformation) was most effective in providing high enantioselectivity [38]. Further, the introduction of substituents at the 3,4, 5 and 6 positions on the aromatic ring of catalyst 39c was not advantageous, and resulted in low enantioselectivity [32,37,39]. The metal ions from first-row transition metals - particularly copper(II) and cobalt(II) - that could form square-planar complexes, produced catalytically active complexes for the asymmetric alkylation of amino ester enolates [38]. 

The reaction of these lithium enolates with alkyl halides is one of the most important C-C bondforming reactions in chemistry. Alkylation of lithium enolates Works with both acyclic and cyclic ketones as well as with acyclic and cyclic esters (lactones). The general mechanism is shown below, alkylation of an ester enolate alkylation of a ketone enolate... 

Highly enantioselective alkylations a to acyclic diene complexes have been developed. Deprotonation of (91) with LDA to form an ester enolate, followed by reaction with iodomethane, gives the alkylated prodnct (92) in excellent yield with 82% ee (Scheme 153). Stereospecific remote alkylation was used in a synthesis toward macrolactin A (Scheme 154). In the synthetic seqnence, the primary... 

Fleming and coworkers and McGarvey and Williams have shown that acyclic ester enolates, e.g. (124), containing relatively strong electron donor groups such as dimethylphenylsilyl and tri-n-butylstan-... 

A quantitative 1,4-chirality transfer is observed in the construction of the acyclic segment C-l to C-ll 11 of the antibiotic ionophore A-23187 (12, calcimycin)441. Both the wanted and unwanted stereoisomer 9 and 10, obtained from the alcohol 8 by pyridinium chlorochromate oxidation followed by Grignard reaction with vinylmagnesium bromide, can be rearranged by the ester enolate procedure simply by changing the reaction conditions to give the stereoisomer 11 with the correct configuration at C-10. 

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. 

An efficient method for the synthesis of 5- and 6-membered cyclic enol ethers from unsaturated esters is first to convert the esters into acyclic olefinic enol ethers, which are then transformed to the desired products by RCM, catalyzed by 8 (Fujimura 1994). Further examples will be found in Table 8.5. 

With these substrates, achiral 1-24 is strongly favoured with Pd catalysts (for other metals, the situation is different) except in special cases. Diazaphos-pholidine-oxazoline 20 shows moderate performance in the alkylation of butenyl acetate compared to the exceptionally good results with SiocPhox phosphonamidate ligands for alkyl- and aryl-substituted substrates. The same type of ligands have also been applied to the alkylation of other challenging substrates such as polyenyl esters and acyclic ketone enolates. ... 

Because of the good results obtained with acyclic substrates, the chelate ester enolate rearrangement was also applied by Kazmaier et al. [80] to the rearrangement of cycloalkenyl glycinates 144 (Scheme 5.2.45). The influence of the ring size as well as the metal salt used for chelation of the ester enolate was investigated and the results are listed in Table 5.2.16. The crude amino acids, obtained by... 

The intramolecular thioacylation of an ester enolate was used for the synthesis of 2-alkylthiopenem carboxylic acid derivatives. Sequential acylations have led to the synthesis of zwitterionic pyrazole-5-thiones from acyclic precursors, whereas 2-ethoxyoxazolidines react with the reagent to afford the products of AAacylation. ... 

With cyclopentenone derivatives, 1,4-addition is observed for the ester enolates of methyl and f-butyl trimethylsilylacetate, although 1,2-addition occurs with acyclic conjugated enals. With a steroidal cyclopentenone substrate, both 1,2- and 1,4-addition were observed. Conjugate addition is observed for the methyl ester with chiral vinyl sulfoxides. High enantioselectivity can be attained (eq 7). ... 

Scheme 2.11 Stereochemistry in the formation of ester enolates Ireland s cyclic model (top) and Heathcock s acyclic model. The latter was originally formulated with HMPA that has been replaced here by DMPU which is known to a similar effect.

The stereoselectivity of the methylation of ketone enolates is determined by the structure of the substrate. Stereoselective methylation of cyclic ketone enolates has been examined in detail and current models reliably predict the stereochemical outcome (eqs 9-11). Diastereoselective methylation of acyclic ketone and ester enolates has been accomplished employing a variety of chiral auxiliaries (eq 12). Efficient catalytic enantioselective methylation of 6,7-dichloro-5-methoxy-l-indanone has been accomplished via a chiral phase-transfer catalyst (eq 13). An enantiomeric excess of 92% was observed when employing Chloromethane as the methylating agent, whereas... 

The coupling reaction between lithium dimethylcuprate and acyclic enol phosphates must be carried out between -47 and -98 C for stereoselective formation of g-methyl-a,g-unsaturated esters. 

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