[reaction: see text] By choosing the right substituents either highly functionalized unusual four-membered ring amino acids or the isomeric pipecolic acid derivatives are obtained in enantiomerically pure form. Starting material is a linear allene-containing amino acid that has been resolved via biocatalysis.

A variety of allylic O,O‐ and N,O‐acetals were synthesized using a mild palladium‐catalyzed coupling of an alcohol or sulfonamide with an alkyl or aryl 1,2‐propadienyl ether. The resulting linear acetals were used for the synthesis of unsaturated rings via ring‐closing metathesis, in which the acetal carbon–a precursor for oxycarbenium or N‐sulfonyliminium ions, respectively–served as a reactive center for further introduction of functional groups. The products–unsaturated oxygen and nitrogen heterocyclic scaffolds–offer multiple opportunities for derivatization as illustrated with the synthesis of substituted dihydropyrans, chromenes, enantiopure tetrahydropyridines and an enantiomerically pure quinolizidine amino acid.

No abstract

A set of both enantiomeric forms of non‐proteinogenic, unsaturated α‐H‐α‐amino acids was efficiently synthesized using a biocatalytic pathway. This route involved the straightforward synthesis of the required unsaturated amino acid amides, followed by resolution with an aminopeptidase present in Pseudomonas putida ATCC 12633 and/or a genetically modified organism, leading to the (S)‐acids and (R)‐amides. Undesired amino acid racemase activity was identified in the wild‐type strain, which was absent in the newly developed organism. The (R)‐amides were hydrolyzed under mild conditions using an amidase present in whole cells from Rhodococcus erythropolis NCIMB 11540 to the (R)‐acids. The viability of this procedure was demonstrated with the multi‐gram synthesis of a variety of unsaturated amino acids in excellent enantiopurity.

A combination of palladium-catalysed N,O-acetal formation, ruthenium-catalysed ring-closing metathesis and Nsulfonyliminium ion-mediated C-C bond formation constitutes an efficient and versatile route to a set of enantiomerically pure 2,6-disubstituted unsaturated pipecolic acid derivatives.