Abstract: Doubled up: a rhodium(III)/copper(II) system co-catalyzes the annulation of benzimides with internal alkynes for the synthesis of indenones (see scheme; Cp*=C(5) Me(5)). The reaction involves an uncommon nucleophilic addition of a transition-metal-carbon bond to an imide moiety. This novel reaction provides a facile route to synthesize indenones from readily available benzimides and internal alkynes.

Abstract: Where HAS you been? A manganese-mediated annulation of 2-isocyanobiaryls with organoboronic acids is developed for the synthesis of a broad range of phenanthridine derivatives. Mechanistic studies indicate that the reaction proceeds by the intramolecular homolytic aromatic substitution (HAS) of an imidoyl radical intermediate.

Abstract: A cooperative catalysis approach for the enantioselective formal [3+2] addition of α,β-unsaturated aldehydes to isatins has been developed. The N-heterocyclic carbene (NHC)-catalyzed homoenolate annulations of β-aryl enals require the addition of lithium chloride for high levels of enantioselectivity. This NHC-catalyzed annulation provides efficient access to the 3-hydroxy indole skeleton and has been applied to the first eantioselective total synthesis of maremycin B.

Abstract: The mild, efficient, and practical intramolecular rhodium-catalyzed C—H/N—H bond functionalization reaction provides isoquinolones with a reverse regioselectivity compared to the reported intermolecular version.

Abstract: A well-defined cationic Ru–H complex catalyzes the dehydrative C–H alkylation reaction of phenols with alcohols to form ortho-substituted phenol products. Benzofuran derivatives are efficiently synthesized from the dehydrative C–H alkenylation and annulation reaction of phenols with 1,2-diols. The catalytic C–H coupling method employs cheaply available phenols and alcohols, exhibits a broad substrate scope, tolerates carbonyl and amine functional groups, and liberates water as the only byproduct.

Abstract: Efficiency in the synthesis of a complex molecular target is greatly dictated by the strategy used for building the key skeletal structure. In particular, fused rings are extremely common structural motifs in natural products and drug molecules, and thus access to these motifs through selective and atom-economic methods is of significant importance. Despite the existence of various elegant stepwise cycloaddition methods for building fused-ring systems, we were particularly intrigued by a catalytic “cut-and-sew” reaction, which involves the oxidative addition of a transition metal to a C C bond (Scheme 1). In this type of reaction, a key intermediate, for example, metallocycle B, is formed when

Abstract: 2,4-Oxazole is an important structural motif in various natural products. An efficient modular synthesis of this structure has been achieved via a [3 + 2] annulation between a terminal alkyne and a carboxamide using a gold-catalyzed oxidation strategy. The postulated reactive intermediate, a terminal α-oxo gold carbene, previously known to be highly electrophilic and hence unlikely to be trapped by stoichiometric external nucleophiles, is coerced to react smoothly with the carboxamide en route to the oxazole ring by a P,N- or P,S-bidentate ligand such as Mor-DalPhos; in stark contrast, often-used ligands such as monodentate phosphines and N-heterocyclic carbenes are totally ineffective. The role of these bidentate phosphines in this reaction is attributed to the formation of a tricoordinated gold carbene intermediate, which is less electrophilic and hence more chemoselective when reacting with nucleophiles. The success in using bidentate phosphine ligands to temper the reactivities of in situ-generated go...

Abstract: A method for the synthesis of bi- and tricyclic amidines has been developed through copper-catalyzed aerobic [3+2]-annulation reaction of N-alkenyl amidines. These cyclic amidines could be converted into mono-benzyl-protected vicinal diamines by the reduction with aluminum hydride.

Abstract: A combination of a chiral N-heterocyclic carbene catalyst and α,β-unsaturated aldehyde leads to a catalytically generated α,β-unsaturated acyl azolium, which participates in a highly enantioselective annulation to give dihydropyranone products. This full account of our investigations into the scope and mechanism of this reaction reveals the critical role of both the type and substitution pattern of the chiral triazolium precatalyst in inducing and controlling the stereochemistry. In an effort to explain why stable enols such as naphthol, kojic acid, and dicarbonyl are uniquely efficient, we have postulated that this annulation occurs via a Coates–Claisen rearrangement that invokes the formation of a hemiacetal prior to a sigmatropic rearrangement. Detailed kinetic investigations of the catalytic annulation are consistent with this mechanistic postulate.

Abstract: Aniline is oxidized into so-called “aniline black”, well-known black pigments that are a mixture of oligomeric materials containing C N double bonds and fused structures. Since such an oxidative fusion reaction of aniline derivatives is usually uncontrollable and provides many isomers and oligomers, it has rarely been recognized as a synthetically useful transformation. However, the selective oxidation of aromatic amines should provide a powerful protocol to combine two aromatic units into one extended p system if the substrates and reaction conditions are carefully designed. Recently, oligoacenes containing pyrazine units have attracted much attention as promising compounds for electron-transporting materials because of their resistance to oxidation relative to the parent oligoacenes. However, the synthetic strategy for this type of azaacenes has mainly been limited to the classic condensation of ortho-quinone derivatives with aromatic ortho-diamines, both of which are often unstable under air. Here we disclose the selective oxidative fusion of 2-aminoanthracenes mediated by 2,3-dichloro-5,6dicyano-1,4-benzoquinone (DDQ) to provide pyrazine-fused bisanthracenes in high yields. Our approach, which makes use of the more-stable monoamino substrates, would be useful for the construction of various pyrazine-fused oligoacenes. Furthermore, we also found that pyrrole-fused bisanthracenes could be formed under slightly modified conditions. The pyrrole-fused dimer can be regarded as an aza[7]helicene with a stable helical conformation that exhibits circular dichroism (CD) and circularly polarized luminescence (CPL) properties. We used 2-aminoanthracene 1a, the two triisopropylsilylethynyl groups of which enhance the solubility of the starting material and products. We found that the oxidation of 1a with DDQ in CHCl3 (Scheme 1) afforded a pyrazine-fused dimer 2a in 43 % yield as a single regioisomer (Table 1, entry 1). The H NMR spectrum of 2 a was indicative of a C2h symmetrical structure, thus indicating a zig-zag-type structure fused by a pyrazine linkage. Furthermore, another product 3a was obtained as a more polar material in 48 % yield. The H NMR spectrum showed 3a was unsymmetrical, with one NH proton signal detected at d = 9.12 ppm. The parent mass ion peaks of 3a at m/z = 1087.6716 (calcd for (C72H97NSi4) + = 1087.6693) suggested a loss of one nitrogen atom from 2a. On the basis of these data, we assigned 3a as a pyrrole-fused dimer. Finally,

Abstract: In this study we performed the total synthesis of the terpene indole alkaloid (+)-ibophyllidine through a pathway involving asymmetric phosphine catalysis, with our novel L-4-hydroxyproline-derived chiral phosphine mediating the key [3 + 2] annulation. Hydrogenation of the [3 + 2] adduct allowed the rapid formation of the stereochemically dense pyrrolidine ring of (+)-ibophyllidine in excellent yield with exceptionally high levels of both diastereo- and enantioselectivity. We constructed the remainder of the pentacyclic skeleton through an intramolecular alkylation and an intramolecular aza-Morita–Baylis–Hillman reaction.

Abstract: The metal-catalyzed oxidative annulation of alkynes with aryl or alkenyl substrates bearing various heteroatom-containing functional groups has proven to be a versatile, efficient, and atom-economic strategy to access a range of valuable heterocyclic products. These processes generally rely upon coordination of the metal center to the heteroatomcontaining functional group, which directs site selective Csp2 H bond cleavage to form the metallacycle A (Scheme 1a). Coordination and migratory insertion of the alkyne and subsequent C X (X = heteroatom) reductive elimination then forms the heterocyclic product. These alkyne oxidative annulations have been complemented by variants that result in the functionalization of two Csp2 H bonds, with or without the assistance of directing groups (Scheme 1b). While these reactions are effective in forming aromatic carboand azacycles, the scope and utility of the general process would be considerably enhanced if variants involving the functionalization of Csp3 H bonds could be developed, thus resulting in partially saturated cyclic products. However, progress in this area has been limited. To our knowledge, the only existing report comes from Nakao, Hiyama and co-workers, who recently described the oxidative annulation of formamides with alkynes, in which an extra equivalent of alkyne acts as the stoichiometric oxidant (Scheme 1c). Herein, we report a new mode of catalytic alkyne oxidative annulation involving the (formal) functionalization of one Csp3 H bond and one Csp2 H bond (Scheme 1d). This ruthenium-catalyzed process results in the formation of indenes, which are important structures in various biologically active compounds and functional materials. A notable feature of this process is the formation of an all-carbon quaternary center, which has not been described previously in alkyne oxidative annulations. At the outset of this work, we hypothesized that aarylcarbonyl compounds might be suitable substrates for alkyne oxidative annulations by virtue of the acidic nature of the a protons, that is, deprotonation would generate an enolate which could serve as an efficient directing group for Csp2 H bond cleavage. 2-Aryl cyclic 1,3-dicarbonyl compounds were selected for investigation on the basis of their high acidity and the permanent close proximity of the aryl and carbonyl groups. This latter feature renders these substrates conformationally predisposed for cyclometallation, thus forming a six-membered metallacycle in readiness for migratory insertion of the alkyne and spiroindene formation. 2-Aryl-1,3-diketones, which exist predominantly in the enol tautomer, were investigated first, and we began with a study of the reaction of 3-hydroxy-2-phenyl-2-cyclohexenone (1a) with 1-phenyl-1-propyne (2a ; Table 1). The Scheme 1. a)–d) Metal-catalyzed oxidative annulation of alkynes.

Abstract: In the presence of chiral ScCl2(SbF6)·BIOP, prepared in situ, and TmsCl as an essential promoter, the desired spirooxindoles are obtained with excellent enantioselectivities at room temperature.

Abstract: A fragment-assembling strategy is used to form oxazoles from aryl acetaldehydes, amines, and molecular oxygen under mild conditions. The transformation is highly efficient with the removal of six hydrogen atoms, including the cleavage of four C(sp(3))-H bonds.

Abstract: Phosphine-catalyzed [3+2] and [4+3]annulation reactions of C,N-cyclic azomethine imines with allenoates have been developed to give a variety of pharmaceutically attractive tetrahydroisoquinoline derivatives in moderate to excellent yields. The two distinct reaction pathways, [3+2] and [4+3]cyclization, depend on the nature of the nucleophilic phosphine and the allenoate. Generally, for α-alkylallenoates, the reactions always proceed with [3 +2]cyclization as the major pathway no matter what phosphine was used; for α-ArCH2-substituted allenoates, the reaction pathway was controlled by the phosphine catalyst used.

Abstract: The first enantiospecific [3+2] annulation of D-A amino-cyclopropanes with ketones is reported herein (see scheme; Phth = phthaloyl). The reaction is catalyzed by 5 mol % of tin(IV) chloride at -78 °C and gives aminotetra-hydrofurans bearing a C5-quaternary stereocenter in high yield, diastereoselectivity and enantio-specificity.

Abstract: Under control: The first example of chiral amino phosphine catalysts for the title reaction between vinyl ketones and N-sulfonyl-1-aza-1,3-dienes has been developed. Under ambient conditions, this protocol provides straightforward access to densely functionalized, enantioenriched tetrahydropyridines with high levels of sterecontrol in good to excellent yields.