Ester enolates Claisen rearrangement

Asymmetric Ireland-Claisen Rearrangements. Chiral enolates derived from the boron complex (5) and allyl esters rearrange with excellent selectivity upon warming to —20 °C for a period of 1-2 weeks (eqs 9 and 10). As discussed above, the geometry of the intermediate enolate can be controlled by appropriate choice of base and solvent, thus allowing access to either syn or anti configuration in the product The reaction can be completed in 2-4 days with little erosion in selectivity when run at 4 °C. 

Claisen rearrangement. The enolate Claisen rearrangement of allyl esters of dipeptides is under chelation control by the addition of MnClj. 

Ireland-Claisen Rearrangement. Silyl enol ethers of allyl esters undergo highly stereoselective Ireland-Claisen rearrangement to afford 4-pentenoic acids. The structure of the ester and the reaction conditions dictate the stereoselectivity. It has seen wide synthetic application, e.g. the construction of unnatural (—)-trichodiene (eq 30). ... 

This effect is the basis of the synthetic importance of ester enolate Claisen rearrangements in which enolates or silyl enol ethers of allylic esters are rearranged into 4-pentenoate esters. 

When ethyl trifluoroacetylacetate is treated with an allylic alkoxide, tran-sesterification is followed by ester enolate Claisen rearrangement m a process that on decarboxylation yields stereospecifically the tnfluoromethyl ketone product [22] (equation 19)... 

CHCI3, reflux (Ireland ester enolate Claisen rearrangement)... 

It is possible to treat ketones with allyl alcohol and an acid catalyst to give y,5-unsaturated ketones directly, presumably by initial formation of the vinylic ethers, and then Claisen rearrangement.In an analogous procedure, the enolates (126) of allylic esters [formed by treatment of the esters with lithium isopropylcyclohex-... 

The stereoselectivity of silyl ketene acetal Claisen rearrangements can also be controlled by specific intramolecular interactions.246 The enolates of a-alkoxy esters adopt the Z-configuration because of chelation by the alkoxy substituent. 

Enolates of allyl esters of a-amino acids are also subject to chelation-controlled Claisen rearrangement.249... 

The ester 7-1 gives alternative stereoisomers when subjected to Claisen rearrangement as the lithium enolate or as the silyl ketene acetal. Analyze the respective transition structures and develop a rationale to explain these results. 

The synthesis in Scheme 13.44 is also based on a carbohydrate-derived starting material. It controlled the stereochemistry at C(2) by means of the stereoselectivity of the Ireland-Claisen rearrangement in Step A (see Section 6.4.2.3). The ester enolate was formed under conditions in which the T -enolate is expected to predominate. Heating the resulting silyl enol ether gave a 9 1 preference for the expected stereoisomer. The... 

Claisen-type rearrangements of ester enolates, ketene acetals, and silyl ketene acetals... 

The C-H functionalization protocol is not limited to the development of surrogate chemistry to enolate transformations. The C-H activation at allylic C-H bonds readily generates 7,6-unsaturated esters, the products of the classic Claisen rearrangement (Figure 6). 

Scheme 2.44 Chelate-controlled Claisen rearrangement of zinc ester enolates 136. Cbz = benzyloxycarbonyl Boc = tert-butoxycarbonyl.

Several applications of this methodology are known. For the determination of the relative configuration of the stereocenter and the axial chiral unit of 71, the product of a diastereoselective ester enolate Claisen rearrangement of 70, with AgBF4 a cycli-zation to 72 was initiated. Then the carboxylic acid was reduced to alcohol 73 and the position of the substituents was investigated by NMR and by the use of NMR shift-reagents (Scheme 15.16) [32], Control experiments ensured the stereospecifi-city of the cyclization and the reduction step. There are further examples of this strategy [33]. 

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

The Claisen rearrangement of O.S-ketal 49 under neutral conditions (refluxing toluene or xylene) leads to the intermediate 50 which undergoes a rearrangement to the diene ester 52 through enolization and a subsequent 1,5-hydrogen shift within intermediate 51 that carries the hydroxy group at the double bond end (equation 16)30. 

Selective protection of the primary alcohol gave 138 (P=TBDMS), which was then esterified with ( )-3-hexenoic acid to produce the key intermediate 139 for cyclization. Ireland ester-enolate Claisen rearrangement and hydrolysis produced a protected hydroxyacid, which, after reduction of the acid and deprotection of the alcohol, yielded meso diol 128 more quickly and efficiently than in the previous synthesis. The meso diol was then converted to the racemate of the lactol pheromone 130 as previously described. 

In one final improvement to the synthesis of the racemate, after it had been shown that even the unnatural enantiomer of the pheromone attracted bugs, the Z-isomer of diene ester 139 was used in the ester-enolate Claisen rearrangement, resulting in a slightly higher yield, and avoiding the use of HMPA as a solvent in that step [113]. 

Only limited precedent exists for the stereoselective enolization and subsequent condensation of a-heteroatom-substituted esters 48a and 48b (eq. [29]). Ireland has examined the enolization process for a-amino ester derivatives where the Claisen rearrangement (chair-preferred transition states) was employed to ascertain enolate geometry (Scheme 10) (43). These results imply that 48a [X = N(CH2Ph)2 ] exhibits only modest selectivity for ( )-enoIate formation under the... 

It has been shown that the Claisen rearrangement of lithium enolates of amino acid enynol esters allows the synthesis of very sensitive y, 5-unsaturated amino acids with conjugated enyne side chains.The chelate-enolate Claisen rearrangement has also been applied to the synthesis of unsaturated polyhydroxylated amino acids, polyhydroxylated piperidines, and unsaturated peptides. ... 

Rearrangement of allyl trimethylsilyl ketene acetal, prepared by reaction of allylic ester enolates with trimethylsilyl chloride, to yield Y,5-unsaturated carboxylic a-cids. The Ireland-Claisen rearrangement seems to be advantageous to the other variants of the Claisen rearrangement in terms of E/Z geometry control and mild conditions. 

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