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Total Synthesis of the Congested Propellane Alkaloid (−)‐Acutumine
Author(s) -
Castle Steven L.
Publication year - 2014
Publication title -
the chemical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.61
H-Index - 78
eISSN - 1528-0691
pISSN - 1527-8999
DOI - 10.1002/tcr.201400005
Subject(s) - chemistry , propellane , regioselectivity , enantioselective synthesis , ketone , radical cyclization , enol , reagent , diketone , total synthesis , enone , stereochemistry , organic chemistry , bicyclic molecule , catalysis
The enantioselective total synthesis of (−)‐acutumine is described. The synthetic strategy was inspired by the premise that the cyclohexenone ring could be derived from an aromatic precursor. After successful construction of a propellane model system, an initial attempt to prepare the spirocyclic subunit was thwarted by incorrect regioselectivity in a radical cyclization. A second‐generation approach involving a radical–polar crossover reaction was successful, and the chemistry developed in the aforementioned model system was then applied to synthesize the natural product. Key reactions included a phenolic oxidation, a diastereoselective ketone allylation utilizing Nakamura's chiral allylzinc reagent, an anionic oxy‐ C ope rearrangement, an acid‐promoted cyclization of a secondary amine onto an α,β‐unsaturated ketal, and a regioselective methyl enol etherification of a 1,3‐diketone.