Sukbok Chang

Recent advances in olefin metathesis and its application in organic synthesis

Abstract Recent advances in olefin metathesis, focusing on the areas of ring-closing olefin metathesis (RCM) and cross metathesis, are reviewed. Among numerous complexes which show catalytic activities in olefin metathesis, recently developed well-defined [Mo] and [Ru] catalyst systems have proven to be very efficient and tolerant of many functional groups. Examples of RCM are organized into the areas of medium or macrocyclizations, peptide chemistry, tandem ring-opening/ring-closing reactions, and RCM mediated rearrangements. Variation of substrates such as in polymer bound forms has been discussed. Applications of acyclic metathesis and ring-opening cross metathesis are also included.

Palladium-catalyzed C-H functionalization of pyridine N-oxides: Highly selective alkenylation and direct arylation with unactivated arenes

Two catalytic protocols of the oxidative C-C bond formation have been developed on the basis of the C-H bond activation of pyridine N-oxides. Pd-catalyzed alkenylation of the N-oxides proceeds with excellent regio-, stereo-, and chemoselectivity, and the corresponding ortho-alkenylated N-oxide derivatives are obtained in good to excellent yields. Direct cross-coupling reaction of pyridine N-oxides with unactivated arene was also developed in the presence of Pd catalyst and Ag oxidant, which affords ortho-arylated pyridine N-oxide products with high site-selectivity.

Transition-Metal-Catalyzed C–N Bond Forming Reactions Using Organic Azides as the Nitrogen Source: A Journey for the Mild and Versatile C–H Amination

Owing to the prevalence of nitrogen-containing compounds in functional materials, natural products and important pharmaceutical agents, chemists have actively searched for the development of efficient and selective methodologies allowing for the facile construction of carbon-nitrogen bonds. While metal-catalyzed C-N cross-coupling reactions have been established as one of the most general protocols for C-N bond formation, these methods require starting materials equipped with functional groups such as (hetero)aryl halides or their equivalents, thus generating stoichiometric amounts of halide salts as byproducts. To address this aspect, a transition-metal-catalyzed direct C-H amination approach has emerged as a step- and atom-economical alternative to the conventional C-N cross-coupling reactions. However, despite the significant recent advances in metal-mediated direct C-H amination reactions, most available procedures need harsh conditions requiring stoichiometric external oxidants. In this context, we were curious to see whether a transition-metal-catalyzed mild C-H amination protocol could be achieved using organic azides as the amino source. We envisaged that a dual role of organic azides as an environmentally benign amino source and also as an internal oxidant via N-N2 bond cleavage would be key to develop efficient C-H amination reactions employing azides. An additional advantage of this approach was anticipated: that a sole byproduct is molecular nitrogen (N2) under the perspective catalytic conditions. This Account mainly describes our research efforts on the development of rhodium- and iridium-catalyzed direct C-H amination reactions with organic azides. Under our initially optimized Rh(III)-catalyzed amination conditions, not only sulfonyl azides but also aryl- and alkyl azides could be utilized as facile amino sources in reaction with various types of C(sp(2))-H bonds bearing such directing groups as pyridine, amide, or ketoxime. More recently, a new catalyst system using Ir(III) species was developed for the direct C-H amidation of arenes and alkenes with acyl azides under exceptionally mild conditions. As a natural extension, amidation of primary C(sp(3))-H bonds could also be realized on the basis of the superior activity of the Cp*Ir(III) catalyst. Mechanistic investigations revealed that a catalytic cycle is operated mainly in three stages: (i) chelation-assisted metallacycle formation via C-H bond cleavage; (ii) C-N bond formation through the in situ generation of a metal-nitrenoid intermediate followed by the insertion of an imido moiety to the metal carbon bond; (iii) product release via protodemetalation with the concomitant catalyst regeneration. In addition, this Account also summarizes the recent advances in the ruthenium- and cobalt-catalyzed amination reactions using organic azides, developed by our own and other groups. Comparative studies on the relative performance of those catalytic systems are briefly described.

Intramolecular Oxidative C−N Bond Formation for the Synthesis of Carbazoles: Comparison of Reactivity between the Copper-Catalyzed and Metal-Free Conditions

New synthetic procedures for intramolecular oxidative C-N bond formation have been developed for the preparation of carbazoles starting from N-substituted amidobiphenyls under either Cu-catalyzed or metal-free conditions using hypervalent iodine(III) as an oxidant. Whereas iodobenzene diacetate or bis(trifluoroacetoxy)iodobenzene alone undergoes the reaction to provide carbazole products in moderate to low yields, combined use of copper(II) triflate and the iodine(III) species significantly improves the reaction efficiency, giving a more diverse range of products in good to excellent yields. On the basis of mechanistic studies including kinetic profile, isotope effects, and radical inhibition experiments, the copper species is proposed to catalytically activate the hypervalent iodine(III) oxidants. The synthetic utility of the present approach was nicely demonstrated in a direct synthesis of indolo[3,2-b]carbazole utilizing a double C-N bond formation.

Rhodium-Catalyzed Intermolecular Amidation of Arenes with Sulfonyl Azides via Chelation-Assisted C–H Bond Activation

We report the direct amidation of arene C-H bonds using sulfonyl azides as the amino source to release N(2) as the single byproduct. The reaction is catalyzed by a cationic rhodium complex under external oxidant-free conditions in the atmospheric environment. A broad range of chelate group-containing arenes are selectively amidated with excellent functional group tolerance, thus opening a new avenue to practical intermolecular C-N bond formation.

Intermolecular oxidative C-N bond formation under metal-free conditions: control of chemoselectivity between aryl sp2 and benzylic sp3 C-H bond imidation.

A new synthetic approach toward intermolecular oxidative C-N bond formation of arenes has been developed under transition-metal-free conditions. Complete control of chemoselectivity between aryl sp(2) and benzylic sp(3) C-H bond imidation was achieved by the choice of nitrogen sources, representatively being phthalimide and dibenzenesulfonimide, respectively.

Rhodium-catalyzed selective olefination of arene esters via C-H bond activation.

A new catalytic procedure of ortho-olefination of benzoates and benzaldehydes has been developed. Ester and carboxaldehyde units were revealed to be effective chelating groups in focusing the activation of aryl C-H bonds ortho to the directing moieties under the Rh-catalyzed oxidative conditions. The reaction is highly regioselective with a range of benzoates and benzaldehydes enabling the efficient olefination with acrylates, acrylic acid, and styrenes.

Transition Metal-Catalyzed C–H Amination: Scope, Mechanism, and Applications

Catalytic transformation of ubiquitous C-H bonds into valuable C-N bonds offers an efficient synthetic approach to construct N-functionalized molecules. Over the last few decades, transition metal catalysis has been repeatedly proven to be a powerful tool for the direct conversion of cheap hydrocarbons to synthetically versatile amino-containing compounds. This Review comprehensively highlights recent advances in intra- and intermolecular C-H amination reactions utilizing late transition metal-based catalysts. Initial discovery, mechanistic study, and additional applications were categorized on the basis of the mechanistic scaffolds and types of reactions. Reactivity and selectivity of novel systems are discussed in three sections, with each being defined by a proposed working mode.

Rhodium-Catalyzed Direct CH Amination of Benzamides with Aryl Azides: A Synthetic Route to Diarylamines†

No muss, no fuss: A rhodium-catalyzed direct intermolecular C-H amination of benzamides and ketoximes using aryl azides as the amine source has been developed. The reaction exhibits a broad substrate scope with excellent functional-group tolerance, requires no external oxidants, releases N(2) as the only by-product, and produces diarylamines in high yields.

Silver-mediated direct amination of benzoxazoles: tuning the amino group source from formamides to parent amines.

The construction of C N bonds of heteroaromatic compounds is a highly important transformation in synthetic chemistry since it can offer nitrogen-containing molecules of great interest in biological, pharmaceutical, and materials sciences. During the past decades, remarkable progresses have been made in the metal-facilitated C N bond-forming reactions such as hydroamination or oxidative amidation of double or triple bonds as well as the Buchwald–Hartwigtype cross couplings. Despite these significant advances, direct installation of amino groups or their surrogates on aryl or alkyl C H bonds is still challenging. To meet this demand, a new approach involving oxidative addition of amino or amido moieties into hydrocarbons has been extensively studied. 6] In particular, site-selective amination of preorganized arenes through catalytic C H bond activation was recently developed. An ortho-selective amination of naphthols through thermal cleavage of disubstituted hydrazines was also reported. Most recently, Mori and co-workers have reported an oxidative amination of azoles using copper salts at high temperature ( 140 8C). Herein, we describe an unprecedented silver-mediated C N bond formation of benzoxazoles by decarbonylative coupling with formamides. On the basis of mechanistic considerations, we have also developed a direct amination protocol with parent amines under very mild reaction conditions. In line with our recent efforts on metal-catalyzed C H bond functionalization, we wondered whether subjection of electron-rich heteroarenes to Pd/Ag-catalytic systems in the presence of formamides could provide amidated products (Scheme 1). To our surprise, when benzoxazole (1a) was treated with N,N-dimethylformamide (DMF) using the Pd(OAc)2/Ag2CO3 system in the presence of an acetic acid additive, 2-aminated benzoxazole 2a was obtained as a single product, albeit in moderate yield. In contrast, no amidated product 3a was observed under other reaction conditions examined. Subsequent studies revealed that the unexpected decarbonylative amination reaction also proceeded even in the absence of the palladium catalyst and with slightly higher yields. Encouraged by these preliminary result, we subsequently tried to optimize the decarbonylative amination conditions using benzoxazole (1a) in neat DMF (40 equiv), as shown in Table 1. Although no desired product was obtained in the absence of the silver salt or the acid additives (entries 1 and 2), addition of certain types of carboxylic acids promoted the transformation in the presence of silver salts (entries 3–8). Among various acids examined, p-anisic acid turned out to be most effective for the amination reaction (entry 8). Catalytic amounts of Ag2CO3 did not furnish the desired product (entry 9), thus indicating that the use of stoichiometric amounts of silver salts is essential for smooth conversion under these reaction conditions. In addition, other silver sources such as Ag2O, AgOAc, AgOTf (Tf = triflate), or AgF (entry 10) were less effective when compared to Ag2CO3. [13] Scheme 1. Decarbonylative amination of benzoxazole (1a).