Asymmetric Organocatalytic Direct C(sp2)?H/C(sp3)?H Oxidative Cross‐Coupling by Chiral Iodine Reagents

An asymmetric organocatalytic direct C H/C H oxidative coupling reaction of N¹,N³‐diphenylmalonamides has been well established by using chiral organoiodine compounds as catalysts, wherein four C H bonds were stereoselectively functionalized to give structurally diverse spirooxindoles with high levels of enantioselectivity. More importantly, the findings indicated that chiral hypervalent organoiodine reagents can serve as alternative catalysts for the creation of enantioselective functionalization of inactive C H bonds.     

The Liebeskind–Srogl C?C Cross‐Coupling Reaction

New kid on the block : The cross‐coupling of thioorganic compounds with boronic acids under neutral conditions in the presence of catalytic palladium(0) and a stoichiometric amount of a copper(I) oxygenate has emerged as a very useful method for the construction of C C bonds (see scheme). This intriguing and mechanistically unprecedented base‐free coupling has distinct advantages, in particular when traditional Pd⁰‐catalyzed cross‐coupling is not possible.

     

Tandem Catalytic C(sp3)?H Amination/Sila‐Sonogashira–Hagihara Coupling Reactions with Iodine Reagents

A new tandem C N and C C bond‐forming reaction has been achieved through Rh^II/Pd⁰ catalysis. The sequence first involves an iodine(III) oxidant, then the in situ generated iodine(I) by‐product is used as a coupling partner. The overall process demonstrates the synthetic value of iodoarenes produced in trivalent iodine reagent mediated oxidations.     

Site‐Differentiated Polyboron Arenes Prepared by Direct C?H Borylation and Their Highly Selective Suzuki–Miyaura Cross‐Coupling Reactions

Di‐ and polyboron (hetero)arenes, site‐differentiated with MIDA boronyl (MIDA=N‐methyliminodiacetic acid) and pinacolato boronyl (Bpin), were prepared by an iridium‐catalyzed direct C H borylation of readily available (hetero)aryl MIDA boronates. The excellent synthetic uses of these multisite nucleophiles were demonstrated by the high‐yield production of a variety of multifunctionalized poly(hetero)arenes with the highly chemoselective Suzuki–Miyaura coupling (SMC) of the Bpin moiety being an essential step.     

Copper‐Catalyzed Intramolecular C(sp3)?H and C(sp2)?H Amidation by Oxidative Cyclization

The first copper‐catalyzed intramolecular C(sp³) H and C(sp²) H oxidative amidation has been developed. Using a Cu(OAc)₂ catalyst and an Ag₂CO₃ oxidant in dichloroethane solvent, C(sp³) H amidation proceeded at a terminal methyl group, as well as at the internal benzylic position of an alkyl chain. This reaction has a broad substrate scope, and various β‐lactams were obtained in excellent yield, even on gram scale. Use of CuCl₂ and Ag₂CO₃ under an O₂ atmosphere in dimethyl sulfoxide, however, leads to 2‐indolinone selectively by C(sp²) H amidation. Kinetic isotope effect (KIE) studies indicated that C H bond activation is the rate‐determining step. The 5‐methoxyquinolyl directing group could be removed by oxidation.     

Site‐Differentiated Polyboron Arenes Prepared by Direct C?H Borylation and Their Highly Selective Suzuki–Miyaura Cross‐Coupling Reactions

Di‐ and polyboron (hetero)arenes, site‐differentiated with MIDA boronyl (MIDA=N‐methyliminodiacetic acid) and pinacolato boronyl (Bpin), were prepared by an iridium‐catalyzed direct C H borylation of readily available (hetero)aryl MIDA boronates. The excellent synthetic uses of these multisite nucleophiles were demonstrated by the high‐yield production of a variety of multifunctionalized poly(hetero)arenes with the highly chemoselective Suzuki–Miyaura coupling (SMC) of the Bpin moiety being an essential step.     

Copper‐Catalyzed Radical/Radical C?H/P?H Cross‐Coupling: α‐Phosphorylation of Aryl Ketone O‐Acetyloximes

The selective radical/radical cross‐coupling of two different organic radicals is a great challenge due to the inherent activity of radicals. In this paper, a copper‐catalyzed radical/radical C H/P H cross‐coupling has been developed. It provides a radical/radical cross‐coupling in a selective manner. This work offers a simple way toward β‐ketophosphonates by oxidative coupling of aryl ketone o‐acetyloximes with phosphine oxides using CuCl as catalyst and PCy₃ as ligand in dioxane under N₂ atmosphere at 130 °C for 5 h, and yields ranging from 47 % to 86 %. The preliminary mechanistic studies by electron paramagnetic resonance (EPR) showed that, 1) the reduction of ketone o‐acetyloximes generates iminium radicals, which could isomerize to α‐sp³‐carbon radical species; 2) phosphorus radicals were generated from the oxidation of phosphine oxides. Various aryl ketone o‐acetyloximes and phosphine oxides were suitable for this transformation.     

Enantioselective ortho‐C?H Cross‐Coupling of Diarylmethylamines with Organoborons

The commonly used para‐nitrobenzenesulfonyl (nosyl) protecting group is employed to direct the C H activation of amines for the first time. An enantioselective ortho‐C H cross‐coupling between nosyl‐protected diarylmethylamines and arylboronic acid pinacol esters has been achieved utilizing chiral mono‐N‐protected amino acid (MPAA) ligands as a promoter.     

Ligand‐Promoted Borylation of C(sp3)?H Bonds with Palladium(II) Catalysts

A quinoline‐based ligand effectively promotes the palladium‐catalyzed borylation of C(sp³) H bonds. Primary β‐C(sp³) H bonds in carboxylic acid derivatives as well as secondary C(sp³) H bonds in a variety of carbocyclic rings, including cyclopropanes, cyclobutanes, cyclopentanes, cyclohexanes, and cycloheptanes, can thus be borylated. This directed borylation method complements existing iridium(I)‐ and rhodium(I)‐catalyzed C H borylation reactions in terms of scope and operational conditions.     

Chemo‐ and Regioselective C(sp3)?H Arylation of Unactivated Allylarenes by Deprotonative Cross‐Coupling

The combination of aryl bromides, allylbenzene, base and a palladium catalyst usually results in a Heck reaction. Herein we combine these same reagents, but override the Heck pathway by employing a strong base. In the presence of LiN(SiMe₃)₂, allylbenzene derivatives undergo reversible deprotonation. Transmetalation of the resulting allyllithium intermediate to LPdAr(Br) and reductive elimination provide the 1,1‐diarylprop‐2‐enes, which are not accessible by the Heck reaction. The regioselectivity in this deprotonative cross‐coupling process is catalyst‐controlled and very high.     

Catalytic Functionalization of C(sp2)?H and C(sp3)?H Bonds by Using Bidentate Directing Groups

C? H bonds are ubiquitous in organic compounds. It would, therefore, appear that direct functionalization of substrates by activation of C? H bonds would eliminate the multiple steps and limitations associated with the preparation of functionalized starting materials. Regioselectivity is an important issue because organic molecules can contain a wide variety of C? H bonds. The use of a directing group can largely overcome the issue of regiocontrol by allowing the catalyst to come into proximity with the targeted C? H bonds. A wide variety of functional groups have been evaluated for use as directing groups in the transformation of C? H bonds. In 2005, Daugulis reported the arylation of unactivated C(sp³)? H bonds by using 8‐aminoquinoline and picolinamide as bidentate directing groups, with Pd(OAc)₂ as the catalyst. Encouraged by these promising results, a number of transformations of C? H bonds have since been developed by using systems based on bidentate directing groups. In this Review, recent advances in this area are discussed.     

Stereodivergent Synthesis of Arylcyclopropylamines by Sequential C?H Borylation and Suzuki–Miyaura Coupling

A step‐economical and stereodivergent synthesis of privileged 2‐arylcyclopropylamines (ACPAs) through a C(sp³) H borylation and Suzuki–Miyaura coupling sequence has been developed. The iridium‐catalyzed C H borylation of N‐cyclopropylpivalamide proceeds with cis selectivity. The subsequent B‐cyclopropyl Suzuki–Miyaura coupling catalyzed by [PdCl₂(dppf)]/Ag₂O proceeds with retention of configuration at the carbon center bearing the Bpin group, while epimerization at the nitrogen‐bound carbon atoms of both the starting materials and products is observed under the reaction conditions. This epimerization is, however, suppressed in the presence of O₂. The present new ACPA synthesis results in not only a significant reduction in the steps required for making ACPA derivatives, but also the ability to access either isomer (cis or trans) by simply changing the atmosphere (N₂ or O₂) in the coupling stage.     

Redox‐Neutral Rhodium‐Catalyzed C?H Functionalization of Arylamine N‐Oxides with Diazo Compounds: Primary C(sp3)?H/C(sp2)?H Activation and Oxygen‐Atom Transfer

An unprecedented rhodium(III)‐catalyzed regioselective redox‐neutral annulation reaction of 1‐naphthylamine N‐oxides with diazo compounds was developed to afford various biologically important 1H‐benzo[g]indolines. This coupling reaction proceeds under mild reaction conditions and does not require external oxidants. The only by‐products are dinitrogen and water. More significantly, this reaction represents the first example of dual functiaonalization of unactivated a primary C(sp³) H bond and C(sp²) H bond with diazocarbonyl compounds. DFT calculations revealed that an intermediate iminium is most likely involved in the catalytic cycle. Moreover, a rhodium(III)‐catalyzed coupling of readily available tertiary aniline N‐oxides with α‐diazomalonates was also developed under external oxidant‐free conditions to access various aminomandelic acid derivatives by an O‐atom‐transfer reaction.