A pentamethylcyclopentadienylrhodium(III)‐catalyzed regioselective synthesis of indole‐2‐carboxamides is described employing N‐pyrimidylindoles and isocyanates as coupling partners via C H functionalization. A wide variety of indole‐2‐carboxamides can be synthesized via this method under relatively mild conditions with broad functional group tolerance. The effect of various directing group on this transformation was also studied, unveiling the pyrimidyl group as an easily installable and removable directing group.
α‐Substituted β‐acetyl amides could undergo C C bond cleavage to form α‐keto amides when treated with copper(II) chloride (CuCl2) and boron trifluoride diethyl etherate (BF3⋅OEt2) under an oxygen atmosphere. The yield can be increased by the addition of tert‐butyl hydroperoxide which alone can also effect the reaction. The reaction provides a new protocol for the synthesis of α‐keto amides.
A nickel‐catalyzed facile synthesis of structurally diverse five‐membered lactams from aliphatic amides and terminal acetylenes with the assistance of an 8‐aminoquinolyl auxiliary has been achieved. A broad range of terminal acetylenes and aliphatic amides proved to be the efficient coupling partners, furnishing the corresponding lactams in moderate to good yields. The transformation is proven to undergo an oxidative alkynylation followed by the intramolecular annulation process. The methodology can be extended to aromatic amides and acrylamides, which provides an efficient and straightforward protocol for the construction of a variety of isoindolinone and pyrrolidinone derivatives.
An unprecedented palladium(II)‐catalyzed biomimetic aliphatic acyl (‐COR) group transfer was observed from acyl‐α‐peroxycoumarins to the ortho C H sites of directing arenes. Here, the C H activation is associated with a concomitant acyl group transfer via a Pd(II)‐catalyzed, redox‐neutral process. While methods for ortho aroylation (‐COAr) are well documented ortho acylation (‐COR) processes are scarce, hence the present redox‐neutral method is most ideal for o‐acylation of directing substrates.
The copper(I) bromide‐catalyzed intermolecular dehydrogenative amidation of arenes via C H bond activation assisted by a 2‐pyridyl or 1‐pyrazolyl chelating group using air as the terminal oxidant has been achieved at 140 °C. N‐Aryl amides, N‐alkyl amides, benzamide derivatives, imides, and lactams all are good coupling partners to obtain moderate to excellent yields. The amount of solvent is critical for the transformation: both increasing and decreasing the amount of solvent decreased the yield. Notably, the amidation of bimolecular 2‐phenylpyridine with the dual N H bonds of a primary amide proceeded smoothly in one‐pot to afford a good yield under the same conditions. The amidation can be performed with a good yield at the gram scale.
Sequential copper‐catalyzed [3+2] cycloaddition, rhodium‐catalyzed O H insertion, intramolecular 1,8‐addition, and rearrangement starting from 1‐alkynes, N‐sulfonyl azides, and tropolones is demonstrated for the synthesis of the 2‐functionalized aminotropones in one pot. These results indicate that sequential functionalization of O H and C(sp2) O bonds smoothly occurs in the C(sp2) O H bonds of tropolone
A novel and efficient oxidative annulation of 2‐aminobenzamides with nitromethane has been developed for the chemoselective synthesis of N‐substituted 1,2,3‐benzotriazine‐4(3H)‐ones in moderate to excellent yields under transition metal‐free conditions. Two N N bonds were constructed in one pot via C N cleavage of nitromethane, which was selectively employed as the nitrogen synthon. The preliminary mechanistic studies revealed that this protocol proceeded under hypoiodite catalysis generated in situ.
Compared with the well‐known palladium‐catalyzed oxidative dehydrogenation coupling reactions, similar transforms initiated by copper/oxygen have attracted more and more attention. We have investigated a novel construction of heteroaromatic imidazo[1,2‐a]pyridines through copper(I) iodide/boron trifluoride etherate/oxygen‐mediated dehydrogenative reactions of aryl alkyl or alkyl alkyl ketones with 2‐aminopyridines. Four hydrogen atoms are removed and two new C N bonds are formed in one step via the imine formation and oxidative C(sp3) H functionalization.
An efficient rhodium(III)‐catalyzed direct C7 alkynylation of indoline C H bonds with the alkynylated hypervalent iodine reagents has been developed. This reaction proceeds smoothly under mild conditions over a wide structural scope with high site‐selectivity and excellent functional‐group tolerance. N‐Acetyl as well as other N‐acyls served as effective directing groups (DG). This procedure allows for the synthesis of a variety of 7‐alkynyl‐substituted indolines in good to excellent yield. More significantly, C7‐alkynylated indoles through further transformations have been successfully accessed.
In this work an efficient tandem process transforming N‐substituted amidines into secondary amides has been described. The process involves N‐acylurea formation by reaction of the substrate with bis(acyloxy)(phenyl)‐λ3‐iodane followed by isocyanate elimination. The periodinane reagents are obtained from the commercially available phenyliodine(III) diacetate [PhI(OAc)2, (PIDA)] by ligand exchange with carboxylic acids. The N‐substituted amidine substrates are easily synthesized from readily available nitriles. The method is applicable for secondary amide synthesis, based on both aliphatic and (hetero)aromatic amines, including challenging amides consisting of sterically hindered acids and amines. Moreover, the protocol allows one to combine steric bulk with electron deficiency in the target amides (aniline based). Such compounds are difficult to synthesize efficiently based on classical condensation reactions involving carboxylic acids and amines. Overall, the synthetic protocol transforms a nitrile into a secondary amide in both aliphatic and (hetero)aromatic systems.
Rhodium‐catalyzed tandem annulation reactions via olefination and subsequent intramolecular C‐Michael‐type cyclization represent an efficient approach for the direct construction of C C bonds. The simple and atom‐economic strategy produces various alkylation derivatives of 7‐azaindole with a quaternary carbon center from 7‐azaindoles and olefins.
An efficient, green and first catalytic process has been developed for the direct synthesis of amides from readily available petroleum by‐products (methylarenes) and amines using an iron catalyst. In this new catalytic reaction, the methyl group of the methylarene is oxidized to the corresponding aldehyde through non‐directed C H oxidation followed by its oxidative amidation with N‐chloroamine, yielding the carboxylic amide. Oxidation with an iron catalyst, tert‐butyl hydroperoxide (TBHP) as sole oxidant, the synthesis of amides under mild reaction conditions and the utilization of methylarenes as starting material make this methodology novel and environmentally benign.
An efficient phosphaannulation via palladium(II)‐catalyzed C H activation/oxidative cyclization by the 6‐endo mode is reported for the synthesis of 3‐substituted phosphaisocoumarins from the reaction of arylphosphonic acids with unactivated alkenes under aerobic conditions. Also, α,α‐disubstituted benzylphosphonic acids were phosphaannulated with unactivated alkenes, producing phosphaisochromanones having (Z)‐alkylidenyl groups via anti‐phosphoryloxypalladation by the 6‐exo mode.
A general protocol for the chemoselectivity‐controlled C C and C S coupling reactions of di(hetero)aryl disulfides with Grignard reagents catalyzed by ferrocene and palladium acetate has been developed. Ferrocene favored the formation of C S coupled products at low temperature, whereas C C bond couplings were favored when palladium acetate was used. All the reactions proceeded with excellent chemoselectivity and in good yields under mild conditions, and a library of molecules with pyridine and pyrimidine scaffolds was produced.
A direct annulation reaction of N‐(2‐formylaryl)indoles has been developed, which can provide a new entry to biologically and medicinally important indole‐indolone scaffolds via a silver‐catalyzed direct oxidative coupling between aldehyde C H and sp2 C H bonds for the first time. Remarkably, this strategy displayed excellent functional group compatibilities, thereby suggesting its wide potential for applications in developing and synthesizing new drug‐like compounds containing indole‐indolone frameworks.
Dirhodium(II) acetate‐catalyzed reactions of N‐tosylhydrazones with dihydroquinazolinones bearing different types of N H bonds that give N3‐benzyl/alkyl‐2‐arylquinazolin‐4(3H)‐ones through Csp3 N bond formation by oxidative dehydrogenation and insertion of rhodium‐carbenoid into amide N H bond are reported for the first time. This method features good to excellent yields, good functional group tolerance, high regioselectivity and readily available starting materials.
A simple hydrido‐cobalt complex efficiently catalyses the highly regio‐ and stereoselective dimerisation of various terminal arylacetylenes under mild conditions. The corresponding (E)‐1,4‐enynes are obtained as sole isomers with good to excellent yields. DFT calculations revealed that the reaction proceeds via a C H activation/hydrocobaltation pathway.
An efficient method for the synthesis of indole derivatives from readily available pyrimidyl‐substituted anilines and diazo compounds via rhodium(III)‐catalyzed C H bond activation has been developed. This cyclization reaction displays excellent functional group compatibility and regioselectivity, which overcomes some drawbacks of the classical indole synthetic methods and provides a facile approach for the construction of multi‐substituted indole derivatives. The redox‐neutral intermolecular annulation procedure comprises tandem C H bond activation, cyclization, and condensation steps, releasing water and nitrogen as by‐products.
A highly efficient head‐to‐tail dimerization of a styrene was developed using a cationic palladium(II)‐catalyzed selective C C bond forming reaction. The complex [AllylPd(PPh3)]+OTf−, which is believed to generate ‘palladium hydride’ (Pd H), catalyzed the dimerization of various styrenes in excellent yields as single isomers. This Pd(II)‐catalyzed reaction provides a new economical C C bond forming method.
A new copper‐mediated synthesis of α‐sulfonylethanone oximes from styrenes, sodium arylsulfinates and tert‐butyl nitrite (t‐BuONO; TBN) is presented. This intermolecular three‐component method enables the one‐step formation of C N and C S bonds under mild conditions, and represents a new, straightforward approach to α‐sulfonylethanone oximes.
