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Regiodivergent enantioselective C–H functionalization of Boc-1,3-oxazinanes and application to the synthesis of β2 and β3-amino acids
- Source :
- Nature catalysis
- Publication Year :
- 2019
-
Abstract
- β2- and β3-Amino acids are important chiral building blocks for the design of new pharmaceuticals and peptidomimetics. Here we report a straightforward regio- and enantiodivergent access to these compounds using a one-pot reaction composed of sparteine-mediated enantioselective lithiation of a Boc-1,3-oxazinane, transmetallation to zinc and direct or migratory Negishi coupling with an organic electrophile. The regioselectivity of the Negishi coupling was highly ligand-controlled and switchable to obtain the C4- or the C5-functionalized product exclusively. High enantioselectivities were achieved on a broad range of examples, and a catalytic version in chiral diamine was developed using the (+)-sparteine surrogate. Selected C4- and C5-functionalized Boc-1,3-oxazinanes were subsequently converted to highly enantio-enriched β2- and β3-amino acids with the (R) or (S) configuration, depending on the sparteine enantiomer employed in the lithiation step.
- Subjects :
- Article
Subjects
Details
- Language :
- English
- ISSN :
- 25201158
- Volume :
- 2
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Nature catalysis
- Accession number :
- edsair.pmid..........a9179657f642e8e071fa723ee1c79552