4 research outputs found
Palladium-Catalyzed C(sp<sup>3</sup>)–H Arylation of Diarylmethanes at Room Temperature: Synthesis of Triarylmethanes via Deprotonative-Cross-Coupling Processes
Although metal-catalyzed direct arylation reactions of
non- or
weakly acidic C–H bonds have recently received much attention,
chemists have relied heavily on substrates with appropriately placed
directing groups to steer reactivity. To date, examples of intermolecular
arylation of unactivated CÂ(sp<sup>3</sup>)–H bonds in the absence
of a directing group remain scarce. We report herein the first general,
high-yielding, and scalable method for palladium-catalyzed CÂ(sp<sup>3</sup>)–H arylation of simple diarylmethane derivatives with
aryl bromides at room temperature. This method facilitates access
to a variety of sterically and electronically diverse hetero- and
nonheteroaryl-containing triarylmethanes, a class of compounds with
various applications and interesting biological activity. Key to the
success of this approach is an in situ metalation of the substrate
via C–H deprotonation under catalytic cross-coupling conditions,
which is referred to as a deprotonative-cross-coupling process (DCCP).
Base and catalyst identification were performed by high-throughput
experimentation (HTE) and led to a unique base/catalyst combination
[KNÂ(SiMe<sub>3</sub>)<sub>2</sub>/Pd–NiXantphos] that proved
to efficiently promote the room-temperature DCCP of diarylmethanes.
Additionally, the DCCP exhibits remarkable chemoselectivity in the
presence of substrates that are known to undergo O-, N-, enolate-,
and CÂ(sp<sup>2</sup>)–H arylation
Palladium-Catalyzed Direct C–H Arylation of 3‑(Methylsulfinyl)thiophenes
A palladium-catalyzed
direct arylation of (3-thiophene)ÂSÂ(O)ÂMe derivatives
has been developed. This protocol is effective for the selective synthesis
of 2-arylated and 2,5-diarylated sulfinylthiophene derivatives with
as low as 0.5 mol % catalyst loading. Various functional groups are
well tolerated. A method to install two different aryl groups on 3-(methylsulfinyl)Âthiophenes
is also introduced
Positional Selectivity in C–H Functionalizations of 2‑Benzylfurans with Bimetallic Catalysts
Metal-catalyzed
carbon–carbon bond-forming reactions are
a mainstay in the synthesis of pharmaceutical agents. A long-standing
problem plaguing the field of transition metal catalyzed C–H
functionalization chemistry is control of selectivity among inequivalent
C–H bonds in organic reactants. Herein we advance an approach
to direct site selectivity in the arylation of 2-benzylfurans founded
on the idea that modulation of cooperativity in bimetallic catalysts
can enable navigation of selectivity. The bimetallic catalysts introduced
herein exert a high degree of control, leading to divergent site-selective
arylation reactions of both sp<sup>2</sup> and sp<sup>3</sup> C–H
bonds of 2-benzylfurans. It is proposed that the selectivity is governed
by cation−π interactions, which can be modulated by choice
of base and accompanying additives [MNÂ(SiMe<sub>3</sub>)<sub>2</sub>, M = K or Li·12-crown-4]
NiXantphos: A Deprotonatable Ligand for Room-Temperature Palladium-Catalyzed Cross-Couplings of Aryl Chlorides
Although
the past 15 years have witnessed the development of sterically bulky
and electron-rich alkylphosphine ligands for palladium-catalyzed cross-couplings
with aryl chlorides, examples of palladium catalysts based on either <i>triarylphosphine</i> or <i>bidentate phosphine</i> ligands for efficient <i>room temperature</i> cross-coupling
reactions with unactivated aryl chlorides are rare. Herein we report
a palladium catalyst based on NiXantphos, a <i>deprotonatable
chelating aryldiphosphine</i> ligand, to oxidatively add unactivated
aryl chlorides at room temperature. Surprisingly, comparison of an
extensive array of ligands revealed that under the basic reaction
conditions the resultant heterobimetallic Pd–NiXantphos catalyst
system outperformed all the other mono- and bidentate ligands in a
deprotonative cross-coupling process (DCCP) with aryl chlorides. The
DCCP with aryl chlorides affords a variety of triarylmethane products,
a class of compounds with various applications and interesting biological
activity. Additionally, the DCCP exhibits remarkable chemoselectivity
in the presence of aryl chloride substrates bearing heteroaryl groups
and sensitive functional groups that are known to undergo 1,2-addition,
aldol reaction, and <i>O</i>-, <i>N</i>-, enolate-α-,
and CÂ(sp<sup>2</sup>)–H arylations. The advantages and importance
of the Pd–NiXantphos catalyst system outlined herein make it
a valuable contribution for applications in Pd-catalyzed arylation
reactions with aryl chlorides