11 research outputs found
Conversion of Amides into Esters by the Nickel-Catalyzed Activation of Amide C-N Bonds
The amide function is ubiquitous in natural compounds as
well as in man-made molecules and materials. It is generally
very stable and poorly reactive owing to its resonance-stabilized
C–N group that imparts a planar geometry to amides.
In contrast, carboxylic esters are generally reactive under a
variety of mild conditions; therefore, it is not surprising that
a number of direct methods are available to the chemist for
converting esters into amides (amino-de-alkoxylation reaction)
but very few for achieving the opposite transformation.
Recently, Professors Neil Garg and Ken Houk from the University
of California, Los Angeles (UCLA, USA) reported in Nature
a groundbreaking method for converting amides into esters
with a high degree of efficiency
Total syntheses of indolactam alkaloids (−)-indolactam V, (−)-pendolmycin, (−)-lyngbyatoxin A, and (−)-teleocidin A-2
Cine Substitution of Arenes Using the Aryl Carbamate as a Removable Directing Group
An efficient and controlled means to achieve a rare cine substitution of arenes is reported. The methodology relies on the strategic use of aryl <i>O</i>-carbamates as readily removable directing groups for arene functionalization. The removal of aryl carbamates is achieved by employing an air-stable Ni(II) precatalyst, along with an inexpensive reducing agent, to give synthetically useful yields across a range of substrates. The net cine substitution process offers a new strategy for analogue synthesis, which complements the well-established logic for achieving arene functionalization by ipso substitution
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Nickel-Catalyzed Amination of Aryl Chlorides and Sulfamates in 2-Methyl-THF.
The nickel-catalyzed amination of aryl O-sulfamates and chlorides using the green solvent 2-methyl-THF is reported. This methodology employs the commercially available and air-stable precatalyst NiCl2(DME), is broad in scope, and provides access to aryl amines in synthetically useful yields. The utility of this methodology is underscored by examples of gram-scale couplings conducted with catalyst loadings as low as 1 mol % nickel. Moreover, the nickel-catalyzed amination described is tolerant of heterocycles and should prove useful in the synthesis of pharmaceutical candidates and other heteroatom-containing compounds
Total syntheses of indolactam alkaloids (−)-indolactam V, (−)-pendolmycin, (−)-lyngbyatoxin A, and (−)-teleocidin A-2
We report the total syntheses of (-)-indolactam V and the C7-substituted indolactam alkaloids (-)-pendolmycin, (-)-lyngbyatoxin A, and (-)-teleocidin A-2. The strategy for preparing indolactam V relies on a distortion-controlled indolyne functionalization reaction to establish the C4-N linkage, in addition to an intramolecular conjugate addition to build the conformationally-flexible nine-membered ring. The total synthesis of indolactam V then sets the stage for the divergent synthesis of the other targeted alkaloids. Specifically, late-stage sp2-sp3 cross-couplings on an indolactam V derivative are used to introduce the key C7 substituents and the necessary quaternary carbons. These challenging couplings, in addition to other delicate manipulations, all proceed in the presence of a basic tertiary amine, an unprotected secondary amide, and an unprotected indole. Thus, our approach not only enables the enantiospecific total syntheses of four indolactam alkaloids, but also serves as a platform for probing complexity-generating and chemoselective transformations in the context of alkaloid total synthesis
Quantification of the Electrophilicity of Benzyne and Related Intermediates
The determination
of reactivity parameters for short-lived intermediates
provides an indispensable tool for synthetic design. Despite that
electrophilicity parameters have now been established for more than
250 reactive species, the corresponding parameters for benzyne and
related intermediates have not been uncovered. We report a study that
has allowed for the quantification of benzyne’s electrophilicity
parameter. Our approach relies on the strategic use of the diffusion-clock
method and also provides electrophilicity parameters <i>E</i> for other substituted arynes
Nickel‐Catalyzed Activation of Acyl C−O Bonds of Methyl Esters
We report the first catalytic method for activating the acyl C–O bonds of methyl esters through an oxidative addition process. The oxidative addition adducts, formed using nickel catalysis, undergo in situ trapping to provide anilide products. DFT calculations are used to support the proposed reaction mechanism, understand why decarbonylation does not occur competitively, and to elucidate the beneficial role of the substrate structure and Al(OtBu)(3) additive on the kinetics and thermodynamics of the reaction
Nickel-Catalyzed Amination of Aryl Chlorides and Sulfamates in 2‑Methyl-THF
The
nickel-catalyzed amination of aryl <i>O</i>-sulfamates
and chlorides using the green solvent 2-methyl-THF is reported. This
methodology employs the commercially available and air-stable precatalyst
NiCl<sub>2</sub>(DME), is broad in scope, and provides access to aryl
amines in synthetically useful yields. The utility of this methodology
is underscored by examples of gram-scale couplings conducted with
catalyst loadings as low as 1 mol % nickel. Moreover, the nickel-catalyzed
amination described is tolerant of heterocycles and should prove useful
in the synthesis of pharmaceutical candidates and other heteroatom-containing
compounds
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Conversion of amides to esters by the nickel-catalysed activation of amide C-N bonds.
Amides are common functional groups that have been studied for more than a century. They are the key building blocks of proteins and are present in a broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to the resonance stability of the amide bond. Although amides can readily be cleaved by enzymes such as proteases, it is difficult to selectively break the carbon-nitrogen bond of an amide using synthetic chemistry. Here we demonstrate that amide carbon-nitrogen bonds can be activated and cleaved using nickel catalysts. We use this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory calculations provide insight into the thermodynamics and catalytic cycle of the amide-to-ester transformation. Our results provide a way to harness amide functional groups as synthetic building blocks and are expected to lead to the further use of amides in the construction of carbon-heteroatom or carbon-carbon bonds using non-precious-metal catalysis