Rhodium‐Catalyzed Enantioselective Intramolecular CH Silylation for the Syntheses of Planar‐Chiral Metallocene Siloles

Reported herein is the rhodium‐catalyzed enantioselective C? H bond silylation of the cyclopentadiene rings in Fe and Ru metallocenes. Thus, in the presence of (S)‐TMS‐Segphos, the reactions took place under very mild conditions to afford metallocene‐fused siloles in good to excellent yields and with ee values of up to 97 %. During this study it was observed that the steric hindrance of chiral ligands had a profound influence on the reactivity and enantioselectivity of the reaction, and might hold the key to accomplishing conventionally challenging asymmetric C? H silylations.     

Iridium‐Catalyzed Silylation of Five‐Membered Heteroarenes: High Sterically Derived Selectivity from a Pyridyl‐Imidazoline Ligand

The steric effects of substituents on five‐membered rings are less pronounced than those on six‐membered rings because of the difference in bond angles. Thus, the regioselectivities of reactions of five‐membered heteroarenes that occur with selectivities dictated by steric effects, such as the borylation of C?H bonds, have been poor in many cases. We report that the silylation of five‐membered‐ring heteroarenes occurs with high sterically derived regioselectivity when catalyzed by the combination of [Ir(cod)(OMe)]₂ (cod=1,5‐cyclooctadiene) and a phenanthroline ligand or a new pyridyl‐imidazoline ligand that further increases the regioselectivity. The silylation reactions with these catalysts produce high yields of heteroarylsilanes from functionalization at the most sterically accessible C?H bonds of these rings under conditions that the borylation of C?H bonds with previously reported catalysts formed mixtures of products or products that are unstable. The heteroarylsilane products undergo cross‐coupling reactions and substitution reactions with ipso selectivity to generate heteroarenes that bear halogen, aryl, and perfluoroalkyl substituents.     

Iridium‐Catalyzed Regioselective Silylation of Aromatic and Benzylic CH Bonds Directed by a Secondary Amine

Reported herein is an iridium‐catalyzed, regioselective silylation of the aromatic C? H bonds of benzylamines and the benzylic C? H bonds of 2,N‐dialkylanilines. In this process, (hydrido)silyl amines, generated in situ by dehydrogenative coupling of benzylamine or aniline with diethylsilane, undergo selective silylation at the C? H bond γ to the amino group. The products of this silylation are suitable for subsequent oxidation, halogenation, and cross‐coupling reactions to deliver benzylamine and arylamine derivatives.     

Hydrogen Bonding of Fluorinated Saccharides in Solution: F Acting as H‐Bond Acceptor in a Bifurcated H‐Bond of 4‐Fluorinated Levoglucosans

4‐Fluorinated levoglucosans were synthesised to test if OH???F H‐bonds are feasible even when the O???F distance is increased. The fluorinated 1,6‐anhydro‐β‐D ‐glucopyranoses were synthesised from 1,6 : 3,4‐dianhydro‐β‐D ‐galactopyranose ( 8 ). Treatment of 8 with KHF₂ and KF gave 43% of 4‐deoxy‐4‐fluorolevoglucosan ( 9 ), which was transformed into the 3‐O‐protected derivatives 13 by silylation and 15 by silylation, acetylation, and desilylation. 4‐Deoxy‐4‐methyllevoglucosan ( 19 ) and 4‐deoxylevoglucosan ( 21 ) were prepared as reference compounds that can only form a bivalent H‐bond from HO? C(2) to O? C(5). They were synthesised from the ⁱPr₃Si‐protected derivative of 8 . Intramolecular bifurcated H‐bonds from HO? C(2) to F? C(4) and O? C(5) of the 4‐fluorinated levoglucosans in CDCl₃ solution are evidenced by the ¹H‐NMR scalar couplings ^h1J(F,OH) and ³J(H,OH). The OH???F H‐bond over an O???F distance of ca. 3.0 Å is thus formed in apolar solvents, at least when favoured by the simultaneous formation of an OH???O H‐bond.     

Rhodium‐Catalyzed Enantioselective Intramolecular C?H Silylation for the Syntheses of Planar‐Chiral Metallocene Siloles

Reported herein is the rhodium‐catalyzed enantioselective C H bond silylation of the cyclopentadiene rings in Fe and Ru metallocenes. Thus, in the presence of (S)‐TMS‐Segphos, the reactions took place under very mild conditions to afford metallocene‐fused siloles in good to excellent yields and with ee values of up to 97 %. During this study it was observed that the steric hindrance of chiral ligands had a profound influence on the reactivity and enantioselectivity of the reaction, and might hold the key to accomplishing conventionally challenging asymmetric C H silylations.     

Rhodium‐Catalyzed Enantioselective Oxidative [3+2] Annulation of Arenes and Azabicyclic Olefins through Twofold C−H Activation

C?H bond activation is mostly limited to ortho selectivity. Activation of both ortho and meta C?H bonds constitutes a particularly important strategy for annulation, but has rarely been studied in enantioselective systems. Reported herein is rhodium(III)‐catalyzed asymmetric [3+2] transannulation of arenes with 7‐azabenzonorbornadienes. Two distinct classes of arenes have been identified as substrates, and the coupling proceeded with high enantioselectivity and excellent diastereoselectivity through sequential activation of ortho and meta C?H bonds.     

Rhodium‐Catalyzed PIII‐Directed ortho‐C−H Borylation of Arylphosphines

Transition‐metal‐mediated metalation of an aromatic C?H bond that is adjacent to a tertiary phosphine group in arylphosphines via a four‐membered chelate ring was first discovered in 1968. Herein, we overcome a long‐standing problem with the ortho‐C?H activation of arylphosphines in a catalytic fashion. In particular, we developed a rhodium‐catalyzed ortho‐selective C?H borylation of various commercially available arylphosphines with B₂pin₂ through P^III‐chelation‐assisted C?H activation. This discovery is suggestive of a generic platform that could enable the late‐stage modification of readily accessible arylphosphines.     

[RhIII(Cp*)]‐Catalyzed ortho‐Selective Direct C(sp2)H Bond Amidation/Amination of Benzoic Acids by N‐Chlorocarbamates and N‐Chloromorpholines. A Versatile Synthesis of Functionalized Anthranilic Acids

A Rh^III‐catalyzed direct ortho‐C?H amidation/amination of benzoic acids with N‐chlorocarbamates/N‐chloromorpholines was achieved, giving anthranilic acids in up to 85 % yields with excellent ortho‐selectivity and functional‐group tolerance. Successful benzoic acid aminations were achieved with carbamates bearing various amide groups including NHCO₂Me, NHCbz, and NHTroc (Cbz=carbobenzyloxy; Troc=trichloroethylchloroformate), as well as secondary amines, such as morpholines, piperizines, and piperidines, furnishing highly functionalized anthranilic acids. A stoichiometric reaction of a cyclometallated rhodium(III) complex of benzo[h]quinoline with a silver salt of N‐chlorocarbamate afforded an amido–rhodium(III) complex, which was isolated and structurally characterized by X‐ray crystallography. This finding confirmed that the C?N bond formation results from the cross‐coupling of N‐chlorocarbamate with the aryl–rhodium(III) complex. Yet, the mechanistic details regarding the C?N bond formation remain unclear; pathways involving 1,2‐aryl migration and rhodium(V)– nitrene are plausible.     

Rhodium‐Catalyzed Regioselective C7‐Functionalization of N‐Pivaloylindoles

An efficient rhodium‐catalyzed method for direct C? H functionalization at the C7 position of a wide range of indoles has been developed. Good to excellent yields of alkenylation products were observed with acrylates, styrenes, and vinyl phenyl sulfones, whereas the saturated alkylation products were obtained in good yield with α,β‐unsaturated ketones. Both the N‐pivaloyl directing group and the rhodium catalyst proved to be crucial for high regioselectivity and conversion.     

A [4+1] Cyclative Capture Approach to 3H‐Indole‐N‐oxides at Room Temperature by Rhodium(III)‐Catalyzed CH Activation

The rhodium(III)‐catalyzed [3+2] C? H cyclization of aniline derivatives and internal alkynes represents a useful contribution to straightforward synthesis of indoles. However, there is no report on the more challenging synthesis of pharmaceutically important N‐hydroxyindoles and 3H‐indole‐N‐oxides. Reported herein is the first rhodium(III)‐catalyzed [4+1] C? H oxidative cyclization of nitrones with diazo compounds to access 3H‐indole‐N‐oxides. More significantly, this reaction proceeds at room temperature and has been extended to the synthesis of N‐hydroxyindoles and N‐hydroxyindolines.     

Revealing Silylation of C(sp2)/C(sp3)–H Bonds in Arylphosphines by Ruthenium Catalysis

The first aromatic C?H silylation between arylphosphines and hydrosilanes enabled by a ruthenium complex has been developed. The excellent ortho‐selectivity results from a four‐membered metallacyclic intermediate involving phosphorus chelation. The developed system can be extended to the benzylic C?H silylation of arylphosphines. Diverse silylated arylphosphines are produced, exhibiting broad functional group compatibility. Further functionalization of the products under mild conditions renders the formed compounds useful building blocks.     

Catalytic Electrophilic CH Silylation of Pyridines Enabled by Temporary Dearomatization

A C? H silylation of pyridines that seemingly proceeds through electrophilic aromatic substitution (S_EAr) is reported. Reactions of 2‐ and 3‐substituted pyridines with hydrosilanes in the presence of a catalyst that splits the Si? H bond into a hydride and a silicon electrophile yield the corresponding 5‐silylated pyridines. This formal silylation of an aromatic C? H bond is the result of a three‐step sequence, consisting of a pyridine hydrosilylation, a dehydrogenative C? H silylation of the intermediate enamine, and a 1,4‐dihydropyridine retro‐hydrosilylation. The key intermediates were detected by ¹H NMR spectroscopy and prepared through the individual steps. This complex interplay of electrophilic silylation, hydride transfer, and proton abstraction is promoted by a single catalyst.     

Rhodium(III)‐Catalyzed Alkenylation–Annulation of closo‐Dodecaborate Anions through Double B−H Activation at Room Temperature

1,2,3‐Trisubstituted closo‐dodecaborates with B?O, B?N, and B?C bonds as well as a fused borane oxazole ring have been synthesized by rhodium‐catalyzed direct cage B?H alkenylation and annulation of ureido boranes in the first reported example of regioselective B?H bond functionalization of the [B₁₂H₁₂]^2? cage by transition‐metal catalysis. This reaction proceeded at room temperature under ambient conditions and exhibited excellent selectivity for efficient monoalkenylation with good functional‐group tolerance. The urea moiety enabled B?H activation by acting as a directing group, was incorporated in the oxazole ring in situ, and also avoided multiple alkenylation. A possible mechanism is proposed on the basis of the isolation of a rhodium agostic intermediate and control experiments.     

Nitrone Directing Groups in Rhodium(III)‐Catalyzed C−H Activation of Arenes: 1,3‐Dipoles versus Traceless Directing Groups

Functionalizable directing groups (DGs) are highly desirable in C?H activation chemistry. The nitrone DGs are explored in rhodium(III)‐catalyzed C?H activation of arenes and couplings with cyclopropenones. N‐tert‐butyl nitrones bearing a small ortho substituent coupled to afford 1‐naphthols, where the nitrone acts as a traceless DG. In contrast, coupling of N‐tert‐butyl nitrones bearing a bulky ortho group follows a C?H acylation/[3+2] dipolar addition pathway to give bicyclics. The coupling of N‐arylnitrones follows the same acylation/[3+2] addition process but delivers different bicyclics.     

Rhodium(III)‐Catalyzed Selective ortho‐Olefinations of N‐Acyl and N‐Aroyl Sulfoximines by CH Bond Activation

Two new rhodium‐catalyzed oxidative couplings between sulfoximine derivatives and alkenes by regioselective C?H activation, affording ortho‐olefinated (Heck‐type) products, are reported. A synthetic application of the ortho‐alkenylated products into the corresponding cyclic derivatives has been demonstrated, and a mechanistic rational for the rhodium catalysis is presented.     

One‐Pot Synthesis of Highly Substituted Polyheteroaromatic Compounds by Rhodium(III)‐Catalyzed Multiple CH Activation and Annulation

A new method for the synthesis of highly substituted naphthyridine‐based polyheteroaromatic compounds in high yields proceeds through rhodium(III)‐catalyzed multiple C? H bond cleavage and C? C and C? N bond formation in a one‐pot process. Such highly substituted polyheteroaromatic compounds have attracted much attention because of their unique π‐conjugation, which make them suitable materials for organic semiconductors and luminescent materials. Furthermore, a possible mechanism, which involves multiple chelation‐assisted ortho C? H activation, alkyne insertion, and reductive elimination, is proposed for this transformation.     

Rhodium(III)‐Catalyzed Tandem [2+2+2] Annulation–Lactamization of Anilides with Two Alkynoates via Cleavage of Two Adjacent C−H or C−H/C−O bonds

An electron‐deficient Cp^E rhodium(III) complex bearing a cyclopentadienyl ligand with two ethyl ester substituents catalyzes the tandem [2+2+2] annulation–lactamization of acetanilides with two alkynoates via cleavage of adjacent two C?H bonds to give densely substituted benzo[cd]indolones. The reactions of meta‐methoxy‐substituted acetanilides with two alkynoates also provided benzo[cd]indolones via cleavage of adjacent C?H/C?O bonds. Furthermore, 3,5‐dimethoxyacetanilides reacted with two alkynoates to give dearomatized spiro compounds.     

Cobalt‐Catalyzed Tandem C−H Activation/C−C Cleavage/C−H Cyclization of Aromatic Amides with Alkylidenecyclopropanes

A cobalt‐catalyzed chelation‐assisted tandem C?H activation/C?C cleavage/C?H cyclization of aromatic amides with alkylidenecyclopropanes is reported. This process allows the sequential formation of two C?C bonds, which is in sharp contrast to previous reports on using rhodium catalysts for the formation of C?N bonds. Here the inexpensive catalyst system exhibits good functional‐group compatibility and relatively broad substrate scope. The desired products can be easily transformed into polycyclic lactones with m‐CPBA. Mechanistic studies revealed that the tandem reaction proceeds through a C?H cobaltation, β‐carbon elimination, and intramolecular C?H cobaltation sequence.     

Catalytic Asymmetric C −H Functionalization under Photoredox Conditions by Radical Translocation and Stereocontrolled Alkene Addition

This work demonstrates how photoredox‐mediated C(sp³)?H activation through radical translocation can be combined with asymmetric catalysis. Upon irradiation with visible light, α,β‐unsaturated N‐acylpyrazoles react with N‐alkoxyphthalimides in the presence of a rhodium‐based chiral Lewis acid catalyst and the photosensitizer fac‐[Ir(ppy)₃] to provide a C?C bond‐formation product with high enantioselectivity (up to 97 % ee) and, where applicable, with some diastereoselectivity (3.0:1 d.r.). Mechanistically, the synthetic strategy exploits a radical translocation (1,5‐hydrogen transfer) from an oxygen‐centered to a carbon‐centered radical with a subsequent stereocontrolled radical alkene addition.     

Enantioselective Synthesis of C−N Axially Chiral N‐Aryloxindoles by Asymmetric Rhodium‐Catalyzed Dual C−H Activation

The first enantioselective Satoh–Miura‐type reaction is reported. A variety of C?N axially chiral N‐aryloxindoles have been enantioselectively synthesized by an asymmetric rhodium‐catalyzed dual C?H activation reaction of N‐aryloxindoles and alkynes. High yields and enantioselectivities were obtained (up to 99 % yield and up to 99 % ee). To date, it is also the first example of the asymmetric synthesis of C?N axially chiral compounds by such a C?H activation strategy.