The transformation of a readily available molecule to a medicinally relevant functionality is the heart of organic synthesis which literally unfolds new direction in the field of drug discovery and development. Accordingly, synthetic chemistry fraternity is constantly striving to introduce a range of avant-garde techniques to construct an incredibly important fundamental entity like “amide bonds” which connect the amino acids in proteins and exist as a prevalent structural motif in biomolecules. In this context, we want to introduce the concept of cross-electrophile coupling by merging the photoredox and transition metal catalysis to construct carbamides from superabundant (hetero)aryl chlorides or bromides along with commercially feasible carbamoyl chlorides. However, there is barely any report on direct activation of carbamoyl chloride so far. To circumvent the challenge, we employ the intrinsic affinity of silyl radical species towards halogen atom to harness the carbamoyl radical directly from carbamoyl chlorides which is seemingly the first of its kind. The success of this protocol relies on the prior formation of ‘aryl halides to Ni-catalyst’ oxidative addition intermediate that assists in generation of the vital carbamoyl radical. The breadth of application of this technique is significantly demonstrated by the synthesis of a plethora of (hetero)aryl carbamides with diverse functionalities. As stated earlier, we outline the direct utility of this protocol by the late-stage amidation of halide containing drug molecules and pharmacophores.
Practical nickel catalysis for efficient cross-coupling of O,N-chelated diarylborinates with aryl chlorides and mesylates based on air-stable yet readily activated organonickel precursor, trans-NiCl(Ph)(PPh3)2, and sterically unsymmetrical N-heterocyclic carbene in situ generated from imidazolium precursor with trihydrate potassium phosphate in toluene.
AbstractPhenols are important components of pharmaceuticals, biologically active natural products, and materials. Here, we briefly discuss recent advances in catalytic hydroxylation reactions for the synthesis of phenols, with particular attention to our recent work. H2O is proved to be an efficient hydroxide reagent in converting (hetero)aryl halides into the corresponding phenols under synergistic organophotoredox and nickel catalysis. Aryl bromides as well as less reactive aryl chlorides show high reactivity in this catalytic system. This methodology can be applied to the efficient synthesis of diverse phenols and allows the hydroxylation of multifunctional pharmaceutically relevant aryl halides.1 Introduction2 Representative Methods for Transition-Metal-Catalyzed Hydroxylation of (Hetero)Aryl Halides3 Organophotoredox/Ni Dual Catalytic Hydroxylation of Aryl Halides with Water4 Summary and Outlook
A convenient and efficient chiral CuFe2O4@SiO2-Mn(III) Ch.salen nanocatalyst has been
developed for the C-N cross-coupling reactions of aryl halides/ phenylboronic acid with N-heterocyclic
compounds in water and/or DMSO under mild conditions. The catalyst could be applied for the
N-arylation of a variety of nitrogen-containing heterocycles with aryl chlorides, bromides, iodides and
phenylboronic acid under mild conditions. Moderate to good yields were achieved for all substrates.
The structure of catalyst was characterized using various techniques including FT-IR, FE-SEM, EDX,
XRD, TEM and TGA. The catalyst can be simply recovered and reused for several times without significant
loss of activity.
AbstractDevelopment of practical deuteration reactions is highly valuable for organic synthesis, analytic chemistry and pharmaceutic chemistry. Deuterodehalogenation of organic chlorides tends to be an attractive strategy but remains a challenging task. We here develop a photocatalytic system consisting of an aryl-amine photocatalyst and a disulfide co-catalyst in the presence of sodium formate as an electron and hydrogen donor. Accordingly, many aryl chlorides, alkyl chlorides, and other halides are converted to deuterated products at room temperature in air (>90 examples, up to 99% D-incorporation). The mechanistic studies reveal that the aryl amine serves as reducing photoredox catalyst to initiate cleavage of the C-Cl bond, at the same time as energy transfer catalyst to induce homolysis of the disulfide for consequent deuterium transfer process. This economic and environmentally-friendly method can be used for site-selective D-labeling of a number of bioactive molecules and direct H/D exchange of some drug molecules.
Photosensitized Nickel Catalysis Enabled Silyl Radical Mediated Direct Activation of Carbamoyl Chlorides to Access (Hetero)aryl Carbamides
