The routine application of Csp3-hybridized nucleophiles in cross-coupling reactions remains an unsolved challenge in organic chemistry. The sluggish transmetalation rates observed for the preferred organoboron reagents in such transformations are a consequence of the two-electron mechanism underlying the standard catalytic approach. We describe a mechanistically distinct single-electron transfer-based strategy for the activation of organoboron reagents toward transmetalation that exhibits complementary reactivity patterns. Application of an iridium photoredox catalyst in tandem with a nickel catalyst effects the cross-coupling of potassium alkoxyalkyl- and benzyltrifluoroborates with an array of aryl bromides under exceptionally mild conditions (visible light, ambient temperature, no strong base). The transformation has been extended to the asymmetric and stereoconvergent cross-coupling of a secondary benzyltrifluoroborate.
The cross-coupling of sp3-hybridized organoboron
reagents via photoredox/nickel dual catalysis represents a
new paradigm of reactivity for engaging alkylmetallic reagents
in transition-metal-catalyzed processes. Reported here is an investigation
into the mechanistic details of this important transformation using
density functional theory. Calculations bring to light a new reaction
pathway involving an alkylnickel(I) complex generated by addition
of an alkyl radical to Ni(0) that is likely to operate simultaneously
with the previously proposed mechanism. Analysis of the enantioselective
variant of the transformation reveals an unexpected manifold for stereoinduction
involving dynamic kinetic resolution (DKR) of a Ni(III) intermediate
wherein the stereodetermining step is reductive elimination. Furthermore, calculations suggest that the DKR-based stereoinduction
manifold may be responsible for stereoselectivity observed in
numerous other stereoconvergent Ni-catalyzed cross-couplings
and reductive couplings.
Organotrifluoroborates represent an alternative to boronic acids, boronate esters, and organoboranes for use in Suzuki-Miyaura and other transition-metal-catalyzed cross-coupling reactions. The trifluoroborate moiety is stable toward numerous reagents that are often problematic for other boron species. Consequently, remote functional groups within the organotrifluoroborates can be manipulated, while retaining the valuable carbon-boron bond.
An
iridium photocatalyst and visible light facilitate a room temperature,
nickel-catalyzed coupling of (hetero)aryl bromides with activated
α-heterosubstituted or benzylic C(sp3)–H bonds.
Mechanistic investigations on this unprecedented transformation have
uncovered the possibility of an unexpected mechanism hypothesized
to involve a Ni–Br homolysis event from an excited-state nickel
complex. The resultant bromine radical is thought to abstract weak
C(sp3)–H bonds to generate reactive alkyl radicals
that can be engaged in Ni-catalyzed arylation. Evidence suggests that
the iridium photocatalyst facilitates nickel excitation and bromine
radical generation via triplet–triplet energy transfer.
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