Rearrangements enolates, lithium diisopropylamide

S )-l-Mcthyl-2-propcnyl propanoate (90% ee) is rearranged438 according to the Ireland procedure by enolization with lithium diisopropylamide in either tetrahydrofuran or tetrahy-drofuran/23 vol % hcxamethylphosphoric triamide at — 85 °C followed by silylation with either chlorotrimelhylsilanc or /077-butylchloiodimcthylsilane at the same temperature. Rearrangement of the resulting silyl ketene acetals is performed at room temperature for one day followed by hydrolysis with an aqueous hydroxide solution. 

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. 

A further improvement is the ester enolate Carroll rearrangement of the dianion of allylic acetoacetates. generated by treatment with two equivalents of lithium diisopropylamide at — 78 C in tetrahydrofuran100. The dianions rearrange at 20 C to 65 C in 40-80% yield. For an example, see p 3320. 

When the preparation of alkali metal enolates derived from alkanoylphosphonates was attempted by treatment with strong anhydrous bases such as lithium diisopropylamide or sodium hydride, the formation of phosphate phosphonate-type products was observed. This was interpreted in terms of fragmentation of the enolate formed in the first step to ketene and dialkyl phosphite anion (equation 75), and addition of the latter to the carbonyl group of an unreacted acylphosphonate molecules to form a bisphosphonate. Such molecules are known to rearrange to phosphate phosphonates ... 

Astaxanthin (403) can be obtained from 380 by two routes, in both of which the bis-enolate 47 is produced by reaction with lithium diisopropylamide or sodium hexamethyl-disilazane. In the first method, 47 is converted into the bis-silyl enol ether (48) which, after oxidation with peroxyacids, rearrangement to give the astaxanthin bis-silyl ether and acid-catalysed cleavage of the silyl groups, yields free 403 [31]. Alternatively, 47 can be oxidized directly to 403 by reaction with l-phenylsulphonyl-2-phenyloxaziridine [32] (Scheme 10). 

The reaction of lithium diisopropylamide with propargyl acetate 3.559 followed by treatment of the enolate formed with trimethylchlorosilane at —78°C affords ketene acetal 3.561. After heating the reaction mixture to 40°C, the intermediate vinylpropargyl ether 3.560 undergoes the Claisen rearrangement to produce silyl ester 3.561, which after hydrolysis forms allenyl-acetic acid 3.562 with a 50% overall yield (Scheme 3.42) [281]. This reaction is of interest as a synthetic strategy for obtaining the benzoannelated enyne-allene that by radical cyclization forms polycyclic aromatic compounds with an embedded fluorene section [281]. (Scheme 3.43)... 

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