Desymmetrization of meso-bisphosphates using copper catalysis and alkylzirconocene nucleophiles.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30604753.
- Also identified by DOI 10.1038/s41467-018-07871-x and PMC identifier 6318275.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The desymmetrization of meso-compounds is a useful synthetic method, as illustrated by numerous applications of this strategy in natural product synthesis. Cu-catalyzed allylic desymmetrizations enable the enantioselective formation of carbon-carbon bonds, but these transformations are limited in substrate scope and by the use of highly reactive premade organometallic reagents at cryogenic temperatures. Here we show that diverse meso-bisphosphates in combination with alkylzirconium nucleophiles undergo highly regio-, diastereo- and enantio-selective Cu-catalyzed desymmetrization reactions. In addition, C<sub>2</sub>-symmetric chiral bisphosphates undergo stereospecific reactions and a racemic substrate undergoes a Cu-catalyzed kinetic resolution. The reaction tolerates functional groups incompatible with many common organometallic reagents and provides access to a broad range of functionalized carbo- and hetero-cyclic structures. The products bear up to three contiguous stereogenic centers, including quaternary centers and spirocyclic ring systems. We anticipate that the method will be a useful complement to existing catalytic enantioselective reactions.