Rearrangement chelation-controlled Ireland

Several applications of the chelation-controlled Ireland-Claisen rearrangement in natural product syntheses were reported by Burke et al. The syntheses of a series of bicyclic bilactone natural products such as ethisoUde and related structures started with an epimeric mixture ofj8-hydroxy-a-methylene lactone 57 (Scheme 5.2.18) [31]. 

Very recently, Hong et al. [48] used the chelation-controlled Ireland-Claisen rearrangement of 89 in their synthesis of carbovir analogues 91. Herein, again the ring was closed via ring-closing metathesis. 

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. 

Addition of lithium enolate (56) to trifluorocrotonate (55) proceeded smoothly in almost quantitative yields with excellent stereoselectivity. The intramolecular chelation in 57 retards the retro-aldol reaction. On the other hand, nonfluorinated crotonate (59) provided 60 in a poor yield because of the faster retro-aldol reaction [26]. The stereochemistry of the chelated intermediate (57) was proven by trapping 57 as its ketenesilylacetal (61). Pd-catalyzed Ireland-Claisen rearrangement of 61 proceeded stereospecifically to give a single stereoisomer (62), suggesting a rigid control of the three consecutive stereocenters (Scheme 3.12) [27]. 

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