Enantiospecific sp2–sp3 Coupling of ortho‐ and para‐Phenols with Secondary and Tertiary Boronic Esters

The coupling of ortho ‐ and para ‐phenols with secondary and tertiary boronic esters has been explored. In the case of para ‐substituted phenols, after reaction of a dilithio phenolate species with a boronic ester, treatment with Ph₃BiF₂ or Martin's sulfurane gave the coupled product with complete enantiospecificity. The methodology was applied to the synthesis of the broad spectrum antibacterial natural product (−)‐4‐(1,5‐dimethylhex‐4‐enyl)‐2‐methyl phenol. For ortho ‐substituted phenols, initial incorporation of a benzotriazole on the phenol oxygen atom was required. Subsequent ortho ‐lithiation and borylation gave the coupled product, again with complete stereospecificity.     

Transition‐Metal‐Free C(sp2)–C(sp2) Cross‐Coupling of Diazo Quinones with Catechol Boronic Esters

A transition‐metal‐free C(sp²)?C(sp²) bond formation reaction by the cross‐coupling of diazo quinones with catechol boronic esters was developed. With this protocol, a variety of biaryls and alkenyl phenols were obtained in good to high yields under mild conditions. The reaction tolerates various functionalities and is applicable to the derivatization of pharmaceuticals and natural products. The synthetic utility of the method was demonstrated by the short synthesis of multi‐substituted triphenylenes and three bioactive natural products, honokiol, moracin M, and stemofuran A. Mechanistic studies and density functional theory (DFT) calculations revealed that the reaction involves attack of the boronic ester by a singlet quinone carbene followed by a 1,2‐rearrangement through a stepwise mechanism.     

Modular Stereoselective Synthesis of (1→2)‐C‐Glycosides based on the sp2–sp3 Suzuki–Miyaura Reaction

This work reports a modular and rapid approach to the stereoselective synthesis of a variety of α‐ and β‐(1→2)‐linked C‐disaccharides. The key step is a Ni‐catalyzed cross‐coupling reaction of D ‐glucal pinacol boronate with alkyl halide glycoside easily prepared from commercially available D ‐glucal. The products of this sp²–sp³ cross‐coupling reaction can be converted to glucopyranosyl, mannopyranosyl, or 2‐deoxy‐glucopyranosyl C‐mannopyranosides by one‐ or two‐step stereoselective oxidative–reductive transformations. To the best of our knowledge, we demonstrated the first synthetic application of a challenging sp²–sp³ Suzuki‐Miyaura cross‐coupling reaction in carbohydrate chemistry.     

Construction of C(sp2)−C(sp3) Bond between Quinoxalin‐2(1H)‐ones and N‐Hydroxyphthalimide Esters via Photocatalytic Decarboxylative Coupling

A novel visible‐light‐driven decarboxylative coupling of alkyl N‐hydroxyphthalimide esters (NHP esters) with quinoxalin‐2(1H)‐ones has been developed. This C(sp²)?C(sp³) bond‐forming transformation exhibits excellent substrate generality with respect to both the coupling partners. Of note, a series of 3‐primary alkyl‐substituted quinoxalin‐2(1H)‐ones that were difficult to synthesize by previous methods could be obtained in moderate to excellent yields. Additionally, the mild conditions, easy availability of substrates, wide functional group tolerance and operational simplicity make this protocol practical in the synthesis of 3‐alkylated quinoxalin‐2(1H)‐ones.     

Moleküle mit ungewöhnlich langen N(sp2)–Si(sp3)-Bindungen: Synthese und Kristallstrukturen von 1,2-Benzoldisulfonylaminosilanen

Polysulfonylamines. XCIV. Molecules with Unusually Long N(sp²)–Si(sp³) Bonds: Synthesis and Crystal Structures of 1,2-Benzenedisulfonylaminosilanes The following compounds were obtained by metathesis of silver 1,2-benzenedisulfonimide (AgZ) with the appropriate chlorosilanes: ZSiMe₃ ( 4 ), ZSiⁿPr₃, ZSiMe₂ⁿBu, ZSiMe₂(CMe₂–CHMe₂) ( 7 ), (Z)₂SiMe₂ ( 8 ). In the crystal structures of 4 (monoclinic, space group P2₁/n), 7 (monoclinic, P2₁/c) and 8 (monoclinic, P2₁/n), which were determined by low-temperature X-ray diffraction, the molecules adopt the N-silyl form and display unusually long bonds between the trigonal-planar N and the tetrahedrally coordinated Si atoms ( 4 : 182.6, 7 : 184.1, 8 : 177.8 and 180.5 pm). For 7 in CDCl₃ solution, ¹H and ¹³C NMR data indicate N,O-silylotropy. The solid state structures of molecules 4 and 7 strongly suggest that the N–Si bond lengthening in N,N-disulfonylated aminosilanes is mainly induced by the π-acceptor character of the SO₂ groups and not by the occasionally observed coordination expansion of the Si atom through short intramolecular O…Si contacts.     

Silver‐Catalyzed Isocyanide–Isocyanide [3+2] Cross‐Cycloaddition Involving 1,2‐Group Migration: Efficient Synthesis of Trisubstituted lmidazoles

Imidazole ring is an important five‐membered aromatic heterocycle that is widely present in natural products and synthetic molecules. The isocyanide–isocyanide [3+2] cross‐cycloaddition reaction constitutes a straightforward method to access imidazoles starting from the easily available chemicals. So far, only three successive reports are known and all lead to the formation of 1,4‐disubstituted imidazoles. Here, we report the first isocyanide–isocyanide [3+2] cross‐cycloaddition reaction allowing for the formation of 1,4,5‐trisubstituted imidazoles under silver catalysis. An unexpected 1,2‐migration of sulfonyl, alkoxycaybonyl, and carbamoyl groups took place during the cyclization process that is responsible for the formation of trisubstituted imidazoles. This report displayed a mechanistically novel synthetic method toward a variety of imidazole derivatives, which are otherwise difficult to access by conventional methods.     

Stereocontrolled Synthesis of (E)-β,γ-Unsaturated Esters via Palladium-Catalyzed Cross-Coupling of (E)-Alkenylboronic Acids with α-Bromoacetic Esters

The cross-coupling reaction of trans-alkenylboronic acids with a-bromoacetic esters was firstly studied. It was found that using Pd(OAc)2 as catalyst, a bulky electron-rich phospine, (2-dicyclohexylphospino-biphenyl) as ligand, the reaction can be readily accomplished to give specific (E)-b,g-unsaturated esters in high yields.     

Palladium‐Catalyzed Oxidative C≡C Triple Bond Cleavage of 2‐Alkynyl Carbonyl Compounds Toward 1,2‐Dicarbonyl Compounds†

A new, general palladium‐catalyzed oxidative strategy for the cleavage of the C≡C triple bond is presented. By employing PdCl₂, CuBr₂, TEMPO and air as the catalytic system and H₂O as the carbonyl oxygen atom source, a wide range of 2‐alkynyl carbonyl compounds, including 1,3‐disubstituted prop‐2‐yn‐1‐ones, propiolamides and propiolates, lost an alkynyl carbon to access various 1,2‐dicarbonyl compounds, e.g., 1,2‐diones, 2‐keto amides and 2‐keto esters, through Wacker oxidation, intramolecular cyclization and C—C bond cleavage cascades.     

Enantioselective NiH/Pmrox‐Catalyzed 1,2‐Reduction of α,β‐Unsaturated Ketones

The enantioselective 1,2‐reduction of α,β‐unsaturated ketones was achieved using a NiH catalyst in the presence of pinacolborane. This mild process represents a general method to access a wide variety of structurally diverse α‐chiral allylic alcohols in excellent yields and enantioselectivity, as well as very high levels of ambidoselectivity for 1,2‐ over 1,4‐reduction. Furthermore, for reactions on a 10 mmol scale, catalyst loadings as low as 0.5 mol % could be employed to deliver product without any detrimental effect on the yield, enantio‐, or ambidoselectivity.     

ortho‐Directing Chromium Arene Complexes as Efficient Mediators for Enantiospecific C(sp2)–C(sp3) Cross‐Coupling Reactions

A new strategy for the coupling of a broad scope of electronically diverse aromatics to boronic esters is reported. The coupling sequence, which relies on the directed ortho‐lithiation of chromium arene complexes followed by boronate formation and oxidation, occurs with complete ortho‐selectivity and enantiospecificity to give the coupling products in excellent yields and with high functional group tolerance. An intermediate chromium arene boronate complex was characterized by X‐ray, NMR, and IR experiments to elucidate the reaction mechanism.     

MnI/AgI Relay Catalysis: Traceless Diazo‐Assisted C(sp2)–H/C(sp3)–H Coupling to β‐(Hetero)Aryl/Alkenyl Ketones

An unprecedented Mn^I/Ag^I‐relay‐catalyzed C(sp²)?H/C(sp³)?H coupling of (vinyl)arenes with α‐diazoketones is reported, wherein the diazo group was exploited as a traceless auxiliary for control of regioselectivity. Challenging β‐(hetero)aryl/alkenyl ketones were obtained through this operationally simple approach. The cascade process merges denitrogenation, carbene rearrangement, C?H activation, and hydroarylation/hydroalkenylation. The robustness of this method was demonstrated at preparative scale and applied to late‐stage diversification of natural products.     

Metal‐Free and Efficient Epoxidation of α,β‐Unsaturated Ketones with 1,1,2,2‐Tetrahydroperoxy‐1,2‐Diphenylethane as a Powerful Solid Oxidant

1,1,2,2‐Tetrahydroperoxy‐1,2‐diphenylethane was used for the efficient and metal‐free epoxidation of various α,β‐unsaturated ketones, carried out under mild alkaline conditions at room temperature.     

MnO2‐Promoted Oxidative Radical Sulfonylation of Haloalkynes with Sulfonyl Hydrazides: C(sp)–S Bond Formation towards Alkynyl Sulfones

A catalyst‐free oxidative radical sulfonylation of haloalkynes with sulfonyl hydrazides is reported. It represents an example of C(sp)−S bond formation using sulfonyl hydrazides as sulfonyl radical sources. Various alkynyl sulfones were synthesized in moderate to good yields. Having MnO₂ as the oxidant is very critical for this transformation. Remarkably, the self‐coupling reaction of haloalkynes through C(sp)−C(sp) bond formation is significantly inhibited under the standard reaction conditions.     

Reactions of a,ß‐unsaturated N‐benzenesulfonyl Imine – N‐[(2E)‐3‐phenyl‐2‐propen‐1‐ylidene]benzenesulfonamide with Methyllithium

α,β‐Unsaturated N‐benzenesulfonyl imine 1 was treated with 1.1 eq methyllithium to afford 1,2‐addition adduct as a sole product. However, when compound 1 was treated with 2 eq MeLi, 1,2‐addition product, benzenesulfonamide derivative 3 and 2H‐1,2‐benzothiazine 1,1‐dioxide derivatives 4 and 5 were isolated.     

Visible Light Activation of Boronic Esters Enables Efficient Photoredox C(sp2)–C(sp3) Cross‐Couplings in Flow

We report herein a new method for the photoredox activation of boronic esters. Using these reagents, an efficient and high‐throughput continuous flow process was developed to perform a dual iridium‐ and nickel‐catalyzed C(sp²)–C(sp³) coupling by circumventing solubility issues associated with potassium trifluoroborate salts. Formation of an adduct with a pyridine‐derived Lewis base was found to be essential for the photoredox activation of the boronic esters. Based on these results we were able to develop a further simplified visible light mediated C(sp²)–C(sp³) coupling method using boronic esters and cyano heteroarenes under flow conditions.