The
intramolecular Pd(II)-catalyzed alkenylation of aryl homoallyl
ethers constitutes a mild, versatile, and efficient procedure for
the synthesis of highly and diversely substituted chromanes and 2H-chromenes. The use of p-TsOH as an additive
allows more efficient reactions that could be carried out a room temperature
in most cases. The procedure has a wide scope, allowing the synthesis
of alkylidenechromanes and 2H-chromenes substituted
at C-2 or C-3 of the chromene moiety, thus accessing relevant flavenes
and isoflavenes, and even coumarins, in high yields (59 to 91%, 32
examples).
Palladium-catalyzed dehydrogenative coupling is an efficient synthetic strategy for the construction of quinoline scaffolds, a privileged structure and prevalent motif in many natural and biologically active products, in particular in marine alkaloids. Thus, quinolines and 1,2-dihydroquinolines can be selectively obtained in moderate-to-good yields via intramolecular C–H alkenylation reactions, by choosing the reaction conditions. This methodology provides a direct method for the construction of this type of quinoline through an efficient and atom economical procedure, and constitutes significant advance over the existing procedures that require preactivated reaction partners.
Site-selective installation of C−Me bonds remains a powerful and sought-after tool to alter the chemical and pharmacological properties of a molecule. Direct C−H functionalization provides an attractive means of achieving this transformation. Such protocols, however, typically utilize harsh conditions and hazardous methylating agents with poor applicability toward late-stage functionalization. Furthermore, highly monoselective methylation protocols remain scarce. Herein, we report an efficient monoselective, directed ortho-methylation of arenes using N,N,N-trimethylanilinium salts as noncarcinogenic, bench-stable methylating agents. We extend this protocol to d 3 -methylation in addition to the late-stage functionalization of pharmaceutically active compounds. Detailed kinetic studies indicate the rate-limiting in situ formation of MeI is integral to the observed reactivity.
The
use of earth-abundant first-row transition metals, such as
cobalt, in C–H activation reactions for the construction and
functionalization of a wide variety of structures has become a central
topic in synthetic chemistry over the last few years. In this context,
the emergence of cobalt catalysts bearing pentamethylcyclopentadienyl
ligands (Cp*) has had a major impact on the development of synthetic
methodologies. Cp*Co(III) complexes have been proven to possess unique
reactivity compared, for example, to their Rh(III) counterparts, obtaining
improved chemo- or regioselectivities, as well as yielding new reactivities.
This perspective is focused on recent advances on the alkylation and
alkenylation reactions of (hetero)arenes with alkenes and alkynes
under Cp*Co(III) catalysis.
Six- and seven-membered ring-fused,
functionalized cyclopentadienes
can be obtained in moderate to excellent yields by a cascade process
entailing the Au(I)-catalyzed propargyl Claisen rearrangement/Nazarov
cyclization of propargyl vinyl ethers, the hetero-Diels–Alder
reaction with dialkylazodicarboxylates, and the spontaneous conversion
of cycloaddition products into cyclopentadienes by a highly regioselective
cleavage of a C–N bond. Depending on the treatment of the crude
reaction mixtures, two types of products can be obtained: cyclopentadienes
with pendant hydrazine and aldehyde moieties that intramolecularly
react to form hemiaminals are obtained in 43–52% overall yields
when the crude reaction mixtures are left over K2CO3 in a DCM solution. Instead, by reducing in situ the aldehyde group just after addition of the heterodienophile,
the regioselective C–N bond cleavage generates the corresponding
cyclopentadienes bearing a hydrazine and an alcohol appendage in excellent
yields (66–82%) over four steps, all in one pot. Two examples
from the latter class of compounds were also converted into ring-fused,
functionalized cyclopentadienes, bearing a protected amino group,
by the selective N–N cleavage of the hydrazine moiety.
The
first example of Cp*Co(III)-catalyzed intramolecular hydroarylation
of allyl aryl ethers using an amide directing group for the preparation
of 3,3-disubstituted dihydrobenzofurans in high yields is described.
The reaction of the unactivated alkene is completely selective for
the formation of the quaternary center, allowing different substitution
patterns on the aromatic ring and the alkene. The cyclization can
also be extended to the formation of six-membered rings and to N-homoallylindoles.
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