Amino acid allylic esters rearrangement

Deprotonation of N-protected amino acid allylic esters such as 123 with LDA at -78 °C, and subsequent addition of a metal salt (MX ), presumably results in the formation of a chelated metal enolate 123, which undergoes Qaisen rearrangement upon warming to room temperature, giving rise to unsaturated amino acid 124 (Scheme 5.2.36) [66]. 

Kazmaier, U. Synthesis of y,5-unsaturated amino acids via ester enolate Claisen rearrangement of chelated allylic esters. Amino Acids... 

In contrast to the a-oxy- or a-amino-substituted allylic esters, not many examples for a-thio substituted substrates and their application in Claisen rearrangements are described so far (Scheme 5.2.63). Lythegoe et al. applied the Ireland-Claisen rearrangement to the synthesis of a-mercapto acids such as 199 starting from allylic esters 198 [116]. 199 was oxidized and further converted into a,j8-unsaturat-ed esters or subjected to an oxidative degradation. Jones et al. used the Ireland-Claisen rearrangement of 200 in their syntheses of thietan oxides [117]. 

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

The use of a heteroatom a to the ester carbonyl group allows for the formation of a chelate with the metal counterion hence, the geometry of the ester enolate can be assured.336-338358359 This approach was used in the rearrangement of the glycine allylic esters 13 to y,8-unsaturated amino acids in good yields and excellent diastereoselectivity (Scheme 26.13).358 The enantioselectivity could be reversed by using quinidine instead of quinine. 

A related problem is elimination in ester enolates with leaving groups in the -position. Knight and coworkers observed virtually no a-allyl- -amino acid product in the Ireland silyl ester enolate rearrangement of phthalate (213 Scheme 41). Rearrangement of the -methoxycarbonyl analog (214), however, provided methyl ester (215) in a 79 21 mixture of stereoisomers after treatment with etheral diazomethane. 

Allylic esters of A-acyl-a-amino acids can be converted to y,5-unsaturated a-amino acids in moderate to good yields and diastereoselectivities. Thus, the rearrangement of ( )-2-butenyl N-(tcrt-butoxycarbony])glyeinale affords syn- and anh-a-amino acids 1 in 60-65% yield and 90% ds502. 

Claisen rearrangement. The ester enolate Claisen rearrangement of allyl esters of protected amino acids proceeds after replacing the lithium ion with Zn. 

Towards the synthesis of fluorinated amino acids, Konno et al. investigated allylic esters such as 115 (Scheme 5.2.33) [60]. In view of the findings of Bardett et al. [57] that the Ireland-Claisen rearrangement of non-fluorinated allyl esters proceeds stereoselectively, it was very surprising, that the products 116a and 116b were obtained as a diasteromeric rruxture in a ratio of 62 38 (Table 5.2.11, entry 1). 

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