Claisen rearrangement of esters

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. 

Alkylidene cyclohexenes were synthesized stereoselectively from bis-allyl silylketene acetals derived from cyclohexenones93. As shown in equation 66, Ireland Claisen rearrangement of ester 133 gave only E-diene 136. Reaction of 133 with potassium... 

Ester enolate Claisen rearrangement (4, 307- K)8 6, 276-277 7, 209-210). Lithium hexamethyldisilazide is comparable to LDA in combination with HMPT for stereoselective Claisen rearrangement of ester cnolates. ... 

The 1,2-shift of the alkene inherent in the Claisen rearrangement can alter the reactivity of adjacent functional groups. Panek et al. have made extensive use of the Claisen rearrangement of esters of vinyl silanes to afford aUyl silane products which were used in subsequent S reactions (Scheme 4.81) (cf Scheme 4.21) [24]. 

Tab. 5.2.5 Auxiliary-controlled Ireland-Claisen rearrangements of esters 20.

Tab. 5.2.7 Claisen rearrangement of ester 80. 5.2 Chelate Enolate Claisen Rearrangement ... 

Whitesell and Helbling [49] reported on a conversion of allylic alcohols into jS,y-unsaturated esters based on a Claisen rearrangement/oxidative degradation (Scheme 5.2.25). Thus, Claisen rearrangement of ester 92 as the lithium enolate or as the silylenolether afforded a-methoxycarboxylate 93 as a diastereomeric mixture. Degradation by one carbon was effected by the sequence of Wasserman [50] wherein the dianion 94 formed, by subsequent deprotonation with additional LDA, was oxidized with molecular oxygen. 

Scheme 10.5 Claisen rearrangements of ester-substituted allyl vinyl ethers.

Ester Enolate Claisen Rearrangement. LHMDS is comparable to LDA for the stereoselective Ireland-Claisen rearrangement of ester enolates (eq 10). ... 

The Claisen rearrangement of ester enolates continues to provide interesting syntheses of unsaturated acids. Rearrangement of the ester (32) leads to the allyl silane (33) in 61 and 53% yield for two examples protiodesilylation then provides the Se-unsaturated acids (34) in quantitative and 85 % yield, with a ratio of >8 1 of the diastereoisomers when = H and R = Me (Scheme 17). ... 

Details of a closely related study, leading to carbocyclic esters, have also appeared. Reasonable yields and selectivities are obtained in the Claisen rearrangement of ester enolates of derivatives of lactic acid. The ester (38) (Scheme 19) is readily prepared, in optically active form, from menthone, and it undergoes a Claisen rearrangement to give the acid (39) and its C-2 epimer. ... 

Synthetic routes to derivatives of a,p-dehydrotryptophan and to (S)-3,4-dehydroproline are reported. Studies on the Claisen rearrangement of ester enolates of derivatives of a-amino-acids have been described. The amino-ester (288) is converted into the unsaturated amino-acids (289) and (290), in 60—65 % yield, with a ratio of 9 1 respectively (Scheme 142). 

Cartxjxylalion and subsequent allylation of alkyl heterocycles (via Claisen rearrangement of allyl esters)... 

A synthetically valuable reaction sequence is the chlorodifluoroacetylation of various substituted allylic alcohols and the subsequent Reformatskii-Claisen rearrangement of the ester thus formed to interesting 2,2-difluoropentenoic acid derivatives [25] (equation H) Comparable sequences have been reported for ally monofluoroacetates [26] and allyl 3,3,3-trifiuoropropanoates [27] (equations 15 and 16). 

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

Morken et al. developed a reductive Claisen rearrangement of substituted allyl acrylates. The reaction of ( )-hex-2-enyl acrylate 175 was catalyzed by [Rh(COD)Cl]2 (0.25 mol %) and Me-DuPhos (0.5 mol %) with C MeSiH in benzene at 22 °C to give y,8-unsaturated ester 176 with high diastereoselect-ivity, 11 1 (Scheme 46) [80]. The reaction was carried out on a 10 g scale to provide a 70% yield of 176. This reaction was applied to allylic ester 177 to provide 178, which is a key intermediate in the total synthesis of inos-tamycin [24],... 

Claisen rearrangement of glycolates. Two laboratories 2 have reported that allylic glycolate esters undergo Claisen-Ireland rearrangement (6, 276-277) with useful diastereoselectivity. This rearrangement was used in a synthesis of 1, the aggregation pheromone of the European elm bark beetle.1... 

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]. 

The first syntheses of a-allenic a-amino acids [131,133] took advantage of Steg-lich s [134] protocol for the oxazole-Claisen rearrangement of unsaturated N-ben-zoylamino acid esters (Scheme 18.46). Thus, treatment of the propargylic ester 143 with triphenylphosphine and tetrachlormethane furnished the allenic oxazolone 144, which was converted into the amino acid derivative 145 by methanolysis. Stepwise deprotection finally led to the allenic DOPA analog 146, which shows a much higher decarboxylase-inhibiting activity than a-vinyl- and a-ethynyl-DOPA [133],... 

Sattelkau and Eilbracht90 have exploited the Claisen rearrangement of allyl vinyl ethers in their synthesis of several spiro compounds. As shown below in equation 62, 7,9-dimethyl-l,4-dioxa-spiro[4,5]decan-8-one, 118, was converted to a ,/J-unsaturated ester 119 which was reduced to allyl alcohol 120906. Allyl vinyl ether 121 underwent a rhodium-catalyzed Claisen rearrangement to afford 7r,13r-dimethyl-l,4-dioxa-(8rC9)-dispiro[4.2.4.2]tetradecan-10-one (122) in 36% yield. 

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. 

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. ... 

The Claisen rearrangement of allyl vinyl ethers is a classic method for the stereoselective synthesis of y,J-unsaturated esters. The allylic C-H activation is an alternative way of generating the same products [135]. Reactions with silyl-substituted cyclohexenes 197 demonstrate how the diastereoselectivity in the formation of 198 improves (40% to 88% de) for the C-H insertion reactions as the size of the silyl group increases (TMS to TBDPS) (Tab. 14.14). Indeed, in cases where there is good size differentiation between the two substituents at a methylene site, high diastereo- and enantioselectivity is possible in the C-H activation. 

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