Asymmetric synthesis of (1S,2R)-2-aminocyclooctanecarboxylic acid

A highly efficient asymmetric synthesis of (1S,2R)-2-aminocyclooctanecarboxylic acid has been completed. This asymmetric synthesis using cycloocta-1,5-diene as the starting material is achieved in 77% yield via a four-step sequence from tert-butyl cycloocta-1,7-dienecarboxylate 10 where the extra double bond adjacent to the unsaturated ester is essential to improve the yield. Furthermore, the Michael adduct intermediate (1S,2R,αR)-14 could be used towards the synthesis of the natural product tashiromine.

Graphical abstractThe enantioselective synthesis of cis-2-aminocyclooctanecarboxylic acid from cycloocta-1,5-diene is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide

tert-Butyl (1S,2R,αR)-2-N-benzyl-N-α-methylbenzylaminocyclooct-5-enecarboxylateC28H37NO2Ee, de: >95% (NMR)[α]D26=+98.0 (c 1.2, CHCl3)Source of chirality: asymmetric synthesis by addition of chiral lithium amideAbsolute configuration: (1S,2R,αR)

tert-Butyl (1S,2R,αR)-2-N-benzyl-N-α-methylbenzylaminocyclooct-7-enecarboxylateC28H37NO2Ee, de: >95% (NMR)[α]D26=-4.7 (c 0.96, CHCl3)Source of chirality: asymmetric synthesis by addition of chiral lithium amideAbsolute configuration: (1S,2R,αR)

tert-Butyl (1S,2R,αR)-2-N-benzyl-N-α-methylbenzylaminocyclooctanecarboxylateC28H39NO2Ee, de: >95% (NMR)[α]D26=+109 (c 1.0, CHCl3)Source of chirality: asymmetric synthesis by addition of chiral lithium amideAbsolute configuration: (1S,2R,αR)

tert-Butyl (1S,2R)-2-aminocyclooctanecarboxylateC13H25NO2Ee, de: >95% (NMR)[α]D26=-11.2 (c 1.2, CHCl3)Source of chirality: asymmetric synthesis by addition of chiral lithium amideAbsolute configuration: (1S,2R)

(1S,2R)-2-Aminocyclooctanecarboxylic acidC9H17NO2Ee, de: >95% (NMR)[α]D26=-16.5 (c 0.7, H2O)Source of chirality: asymmetric synthesis by addition of chiral lithium amideAbsolute configuration: (1S,2R)