Atropisomeric anilides have received tremendous attention as a novel class of chiral compounds possessing restricted rotation around an N-aryl chiral axis. However, in sharp contrast to the well-studied synthesis of biaryl atropisomers, the catalytic asymmetric synthesis of chiral anilides remains a daunting challenge, largely due to the higher degree of rotational freedom compared to their biaryl counterparts. Here we describe a highly efficient catalytic asymmetric synthesis of atropisomeric anilides via Pd(II)-catalyzed atroposelective C−H olefination using readily available L-pyroglutamic acid as a chiral ligand. A broad range of atropisomeric anilides were prepared in high yields (up to 99% yield) and excellent stereoinduction (up to >99% ee) under mild conditions. Experimental studies indicated that the atropostability of those anilide atropisomers toward racemization relies on both steric and electronic effects. Experimental and computational studies were conducted to elucidate the reaction mechanism and rate-determining step. DFT calculations revealed that the amino acid ligand distortion is responsible for the enantioselectivity in the C−H bond activation step. The potent applications of the anilide atropisomers as a new type of chiral ligand in Rh(III)-catalyzed asymmetric conjugate addition and Lewis base catalysts in enantioselective allylation of aldehydes have been demonstrated. This strategy could provide a straightforward route to access atropisomeric anilides, one of the most challenging types of axially chiral compounds.
Herein, we describe an unprecedented cascade reaction to b-stereogenic g-lactams involving Pd(II)-catalyzed enantioselective aliphatic methylene C(sp 3) À H alkenylationaza-Wacker cyclization through syn-aminopalladation. Readily available 3,3'-substituted BINOLs are used as chiral ligands, providing the corresponding g-lactams with broad scope and high enantioselectivities (up to 98 % ee). Scheme 1. Synthesis of g-lactams through Pd(II)-catalyzed asymmetric methylene C(sp 3)ÀH alkenylation-aza-Wacker cyclization.
It is challenging to develop simple and low cost catalytic systems while maintaining high reactivity and selectivity. An iron-catalyzed intramolecular C−H amination of sulfamate esters using simple and cheap ligands is reported with general substrate scope (31 examples, up to 95% yield). The addition of second ligand, bipyridine, is able to accelerate the reaction and increase the yield. The ready availability of these iron catalysts provides a promising approach to selective introduction of nitrogen into hydrocarbon feedstock.
An
efficient strategy for N/O-(deutero)alkylation of indoles and
phenols with alkoxides/alcohols as the alkylation reagents is described.
The consecutive detosylation/alkylation transformations feature mild
reaction conditions, high ipso-selectivity, and good
functional group tolerance (>50 examples). A one-pot selective
N-alkylation
of unprotected indoles with alcohols and TsCl is also realized. The
application of this method is demonstrated by the introduction of
isotope-labeled (CD3 and 13CH3) groups
using the readily accessible labeled alcohols and the synthesis of
pharmaceuticals.
Nitrogen-containing organic compounds are ubiquitous in natural products, drug molecules and organic intermediates. Therefore, the introduction of nitrogenous functional groups into organic compounds is of great significance. Despite transition metalcatalyzed C-N coupling reaction provided an effcient strategy to access these ntrogen-containing compounds, extra steps are generally required to obtain the pre-functionalized starting materials. Recently, transi-tionmetalcatalyzed C-H amination has emerged as a more atom-and step-economical strategy to construct C-N bonds. Compared to the noble metals (e.g. palladium and rhodium), base metal catalysts, such as copper, cobalt and nickel, have attracted dramatic attentions, due to their earth abundance, cost effectiveness, and unique catalytic activities. Herein, the recent advances in copper-, cobalt-and nickel-catalyzed C-H amination reactions assisted by directing groups were summmarized according to the types of base metals, C-H bonds, and amination reagents with an emphasis on the discussion of various amination reagents and their application. Finally, the limitations and development trend of this research field are analyzed and prospected.
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