Volume 86, Issue 3

Transition-metal-catalyzed C–H functionalizations have emerged as complementary and powerful tools to access molecular complexity from widely available starting materials. Herein, we present a strategy for asymmetric intramolecular Pd(0)-catalyzed C–H functionalizations. The outlined reactivity is based on the cooperative effect between a chiral phosphorous ligand and a carboxylate base acting as a relay of chirality during the enantio-discriminating concerted metalation deprotonation step. This approach allows the enantioselective construction of a range of important semi-saturated chiral nitrogen-containing heterocycles such as indolines, tetrahydroquinolines, and dibenzazepinones.

Two organometallic catalysis studies are presented. The first one deals with the development of a new catalytic agent based on the mixture of a hydride and an iron salt to trigger efficient radical cyclization processes. In a second line of research, we have shown that the use of chiral anions can outperform chiral ligands in a carbocyclization reaction and a [2 + 2 + 2] cycloaddition.

The rhenium-catalyzed reaction of terminal alkynes with imines gives N -alkylideneallylamine derivatives. A diphenylmethyl group as the substituent on the imine nitrogen gave the best result. Deuterium labeling experiments revealed that the regioselective addition of both the hydrogen and the N -alkylideneaminoalkyl group to the terminal alkynes also proceeded stereoselectively. While alkynes bearing primary and secondary alkyl-, vinyl-, and aryl groups were applicable to the catalytic reaction, tertiary alkyl- and silyl-substituted alkynes gave propargylamines. The C–C bond-forming step via the nucleophilic attack of the alkynyl β-carbon on the imine carbon leading to the formation of a vinylidene rhenium species appears to be involved in the catalytic cycle.

A copper-catalyzed regioselective, stereospecific, and enantioselective aminoboration reaction of alkenes with bis(pinacolato)diboron and O -acylated hydroxylamines has been developed to deliver the corresponding β-aminoalkylboranes, which can be important building blocks in organic synthesis. In addition, this methodology has been applied to a formal regioselective hydroamination of styrenes by replacement of the diboron reagent with polymethylhydrosiloxane (PMHS). The catalytic asymmetric hydroamination is also possible by using an appropriate chiral biphosphine ligand.

Since the conference on Organometallic Chemisrty Directed Towards Organic Synthesis (OMCOS) started in 1981, the author has been involved in the invention of novel synthetic reactions for C–C bond formation, taking advantage of organometallic reagents and catalysis. Herein is described a guideline story of how it is done.

C sp3 –I bonds, especially those with β -hydrogen atoms, are a class of challenging substrates for the Pd-catalyzed transformations. The challenges mainly stem from the reluctant oxidative addition of C sp3 −I bond with Pd(0) species and the facile β -H elimination for alkylpalladium intermediate. Herein, Pd-catalyzed reactions from unactivated C sp3 −I bond were discussed.

This manuscript describes the development of Pd- and Ni-catalyzed arylations of unactivated arene C–H bonds using C–O electrophiles. A method for Pd-catalyzed intramolecular C–H arylation is accomplished using inexpensive and readily available tosylates and mesylates as electrophiles. This transformation is efficient for the synthesis of various heterocyclic motifs including furans, carbazoles, indoles, and lactams. Additionally, a protocol for a one-pot sequential tosylation/arylation of phenol derivatives is presented. The use of earth-abundant and inexpensive Ni catalysts for an intramolecular C–H arylation using aryl pivalates as electrophiles is described. Preliminary mechanistic studies for both the Pd- and Ni-catalyzed arylations are discussed.

A novel and efficient nickel-catalyzed oxidative cross-coupling of arylboronic acids with olefins to synthesize 1,2-diarylalkenes has been developed. By employing Ni(acac) 2 as the catalyst, TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) as the oxidant, a variety of arylboronic acids and styrene derivatives could be cross-coupled efficiently to afford the corresponding 1,2-diarylalkenes in moderate-to-good yields. Notably, high E -selectivity of 1,2-diarylalkenes was obtained with the aid of a high temperature of 120°C. Moreover, boric acid esters also proved to be efficient coupling partners. Initial mechanistic studies suggest that this reaction proceeds through a radical pathway.

Were are reporting a highly diastereoselective, transition-metal-free approach of C -aryl glycosides in the pyranoside and furanoside series by the direct coupling of glycosyl halides with diarylzinc reagents in a toluene/di- n -butyl ether solvent mixture.

Acylation is one of the most abundant organic transformations of alcohols (esterification) and amines (amidation). Because of the greater nucleophilicity of the amino group compared to the hydroxyl group and the stability of amides compared to esters, N -acylation occurs predominantly in organic synthetic reactions. We reported that the μ-oxo-tetranuclear zinc cluster Zn 4 (OCOCF 3 ) 6 O efficiently catalyzes highly chemoselective acylation of hydroxyl groups in the presence of primary and secondary alkyl amino groups to afford the corresponding esters in high yields. Not only zinc carboxylate complexes but also various carboxylate complexes of first-row late transition metals, such as Mn, Fe, Co, and Cu, become catalysts for such the hydroxy group-selective acylation in the presence of amines. Among these carboxylate compounds, we found that the combination of an octanuclear cobalt carboxylate cluster [Co 4 (OCOR) 6 O] 2 (R = CF 3 , CH 3 , and t Bu) with nitrogen-containing ligands such as 2,2′-bipyridine show sufficient catalytic activity toward O -selective transesterification. Notably, an alkoxide-bridged dinuclear complex, Co 2 (OCO t Bu) 2 (bpy) 2 (μ 2 -OCH 2 -C 6 H 4 -4-CH 3 ) 2 , was successfully isolated as a key intermediate that proceeds with Michaelis–Menten behavior through an ordered ternary complex mechanism similar to dinuclear metallo-enzymes, suggesting that the formation of alkoxides, followed by coordination of the ester, is responsible for the unique O -selective acylation.

Copper-catalyzed cross-coupling reactions for C–heteroatom bond formation have attracted numerous research groups in the past 15 years aiming at finding more efficient methodologies under milder conditions. The use of auxiliary ligands has tremendously improved Ullmann-type couplings although a general methodology for different heteroatom-nucleophiles is still lacking. Mechanistic insights are seen as a clue for designing new effective, broad-scope and general methodologies. In this review we describe the widely discussed mechanistic options for this reaction and the use of model compounds to unravel key mechanistic aspects for copper-catalyzed C–heteroatom transformations. Stable aryl-Cu(III) species in model systems are shown to be reliable active catalysts in the coupling of a broad nucleophile scope such as phenols, amides, sulfides, selenides, phosphites, halides and also activated methylene susbtrates for carbon–carbon couplings.

C–H and C–O bonds are two of the most abundant chemical bonds in nature. Direct application of C–H and C–O bonds to take place of C–X bonds in cross coupling reactions exhibited numerous advantages since the pre-activation and the emission of harmful wastes can be avoided. In this synopsis, a variety of novel transformations related to cross coupling reactions based on direct C–H and C–O activation are described.

Alkynes substituted with electron-withdrawing groups participated in various intermolecular reactions with olefin substrates, including [4 + 2] annulation of propiolic acids, intermolecular metathesis-type reaction and carboalkoxylation involving allylethers.

A review of recent developments in silver(I)-catalyzed nitrene insertions into olefin and C–H bonds is presented, with a particular emphasis on reactions where the chemoselectivity can be tuned to promote either aziridination or C–H amination. The scope and synthetic utility of various silver catalysts are described, as well as preliminary investigations into the mechanisms of silver-catalyzed aminations.

We review methods that our lab has developed for the generation of Pd-hydrides and the manipulation of these useful intermediates via β-hydride elimination and migratory insertion steps. For a given alkene functionalization reaction, careful understanding of the dynamics of β-hydride elimination, migratory insertion, and transmetallation have allowed for the selective functionalization of Pd-alkyl intermediates. This has afforded us a means by which to transpose palladium to a desired position on a substrate for subsequent functionalization, empowering a number of useful C–H, C–O, and C–C bond-forming reactions.

Seven-membered rings are ubiquitous in natural products and pharmaceutical agents, and their syntheses continue to stimulate the development of novel synthetic methods. The [5 + 2] cycloaddition is one of the most efficient ways to access seven-membered rings since the two-carbon components (alkenes, alkynes, or allenes) are readily available. Prior to our study, however, there was only one type of transition-metal-catalyzed [5 + 2] cycloaddition: the reaction between vinylcyclopropanes and alkenes, alkynes, or allenes. We recently developed a new type of transition-metal-catalyzed [5 + 2] cycloaddition, where the five-carbon building block is 3-acyloxy-1,4-enyne (ACE). Our recent progress on Rh-catalyzed intra- and intermolecular [5 + 2] cycloadditions of ACEs and alkynes is summarized in this article. Using chiral propargylic esters, bicyclic products were prepared in high optical purity by the intramolecular [5 + 2] cycloadditions. Monocyclic seven-membered rings were synthesized by intermolecular [5 + 2] cycloaddition of ACEs and alkynes. Kinetic studies indicated that the rate of this intermolecular cycloaddition was significantly accelerated when the acetate was replaced by dimethylaminobenzoate. DFT calculations suggested that novel metallacycles were generated by a Rh-promoted oxidative cycloaddition of 1,4-enynes accompanied by a 1,2-acyloxy migration of propargylic esters.

A cobalt– N -heterocyclic carbene catalyst allows ortho-alkylation of aromatic imines with unactivated primary and secondary alkyl chlorides and bromides under room-temperature conditions. The scope of the reaction encompasses or complements that of cobalt-catalyzed ortho-alkylation reactions with olefins as alkylating agents that we developed previously. Stereochemical outcomes of secondary alkylation reactions suggest that the reaction involves single-electron transfer from a cobalt species to the alkyl halide to generate the corresponding alkyl radical. A cycloalkylated product obtained by this method can be transformed into unique spirocycles through manipulation of the directing group and the cycloalkyl groups.

Since the early 1950s, the number of international measurement standards for anchoring stable isotope delta scales has mushroomed from 3 to more than 30, expanding to more than 25 chemical elements. With the development of new instrumentation, along with new and improved measurement procedures for studying naturally occurring isotopic abundance variations in natural and technical samples, the number of internationally distributed, secondary isotopic reference materials with a specified delta value has blossomed in the last six decades to more than 150 materials. More than half of these isotopic reference materials were produced for isotope-delta measurements of seven elements: H, Li, B, C, N, O, and S. The number of isotopic reference materials for other, heavier elements has grown considerably over the last decade. Nevertheless, even primary international measurement standards for isotope-delta measurements are still needed for some elements, including Mg, Fe, Te, Sb, Mo, and Ge. It is recommended that authors publish the delta values of internationally distributed, secondary isotopic reference materials that were used for anchoring their measurement results to the respective primary stable isotope scale.