Enantioselective Synthesis of Tertiary Allylic Fluorides by Iridium‐Catalyzed Allylic Fluoroalkylation

Few allylic electrophiles containing two different substituents at a single allyl terminus and none in which one of the two substituents is a heteroatom, have been shown previously to react with iridium catalysts to form substitution products. We report that iridium‐catalysts are uniquely suited to...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2018-10, Vol.57 (40), p.13125-13129
Main Authors: Butcher, Trevor W., Hartwig, John F.
Format: Article
Language:English
Subjects:
allylic fluorides
allylic substitution
Catalysis
Catalysts
Chemical synthesis
Computer applications
Enantiomers
Esters
Fluorides
Fluorine
Intermediates
Iridium
Nucleophiles
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Summary:Few allylic electrophiles containing two different substituents at a single allyl terminus and none in which one of the two substituents is a heteroatom, have been shown previously to react with iridium catalysts to form substitution products. We report that iridium‐catalysts are uniquely suited to form tertiary allylic fluorides enantioselectively by the addition of a diverse range of carbon‐centered nucleophiles at the fluorine‐containing terminus of 3‐fluoro‐substituted allylic esters. The products contain tertiary stereogenic centers bearing a single fluorine, which are isosteric with common tertiary stereocenters containing a single hydrogen. Computational studies reveal the principal steric interactions influencing the stability of endo and exo π‐allyl intermediates formed from 3,3‐disubstituted allylic electrophiles. Fluorine in a tight spot: Highly congested tertiary allylic fluorides were prepared by the allylic substitution of γ‐fluoro allylic electrophiles. Iridium catalysis enabled the branched‐selective and enantioselective allylic fluoroalkylation of hindered, soft nucleophiles, providing access to fluorinated molecules which would be challenging to prepare by other methods.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201807474