Catalytic Enantioselective Boryl and Silyl Substitution with Trifluoromethyl Alkenes: Scope, Utility, and Mechanistic Nuances of Cu–F β‑Elimination

Catalytic enantioselective methods are introduced that
allow access
to a variety of allyl boronates and silanes that contain a difluoroalkene
unit; the resulting products may be used for the preparation of organofluorine
compounds in high enantiomeric purity. Furthermore, a number of key
mechanistic aspects of the transformations have been investigated
and analyzed. Thus, first, an NHC–Cu-catalyzed method for boryl
substitution with F3C-substituted alkenes is introduced.
These processes, unlike the previously reported strategies, are applicable
to alkyl as well as aryl substituted substrates, afford allyl boronates
bearing a difluoroalkene moiety (up to 98% yield and 95:5 er). Second,
the corresponding silyl substitutions, the first reported cases of
their kind, are presented (up to 94% yield and 97:3 er). Third, experimental
and computational (DFT) investigations are described that shed light
on key mechanistic aspects of the catalytic processes. Evidence (X-ray
structures of Cu–alkyl intermediates and kinetic studies) is
put forth illustrating that the initial Cu–boryl and Cu–silyl
addition is significantly faster than the ensuing Cu–F elimination,
and that the latter step can be facilitated by either a mild Lewis
acid (e.g., a Li or Na cation) or a nucleophilic promoter (e.g., an
alkoxide). These findings together with DFT studies demonstrate that
Cu–F β-elimination probably proceeds with anti-stereochemistry.
Representative cases of ways through which the new mechanistic understanding
may be used to rationalize previously disclosed findings, significantly
improve a transformation, or develop new diastereo- and enantioselective
catalytic methods are provided. For example, an explanation is provided
regarding why bisphosphine–Cu complexes do not efficiently
promote boryl substitutions with aryl-substituted substrates, but
the corresponding silyl substitutions are facile, and how the size
of a ligand can impact regioselectivity and efficiency.