Chihiro Tsukano

Palladium-catalyzed cascade process consisting of isocyanide insertion and benzylic C(sp3)-H activation: concise synthesis of indole derivatives.

Synthesis of the indole skeleton was achieved using a Pd-catalyzed cascade process consisting of isocyanide insertion and benzylic C(sp(3))-H activation. It was found that slow addition of isocyanide is effective for reducing the amount of catalyst needed and Ad(2)P(n)Bu is a good ligand for C(sp(3))-H activation. The construction of the tetracyclic carbazole skeleton was also achieved by a Pd-catalyzed domino reaction incorporating alkyne insertion.

Palladium‐Catalyzed Amidation by Chemoselective C(sp3)H Activation: Concise Route to Oxindoles Using a Carbamoyl Chloride Precursor

Quite select: a new strategy was developed for the synthesis of various oxindoles from carbamoyl chlorides. Under the optimum reaction conditions, with Ad(2)PBu as a ligand, tBuCONHOH as an additive, and a CO atmosphere, selective C(sp(3))-H activation proceeded in the presence of a C(sp(2))-H bond. Ad=adamantyl.

Total Syntheses of Complanadines A and B

Naturally occurring dimeric alkaloids often show distinct and/ or improved biological activities compared with those of their monomers. To investigate the details of their biogenesis and bioactivity, it is attractive to synthesize dimeric natural products from their monomers, in the same way as nature may do. This approach is even more challenging when the dimer is unsymmetrical, because it requires position-controlled union of the two monomers. Complanadines, isolated from the club moss Lycopodium complanatum by Kobayashi et al. , are dimeric Lycopodium alkaloids (Scheme 1). These compounds are unsymmetrical as a result of a C2 C3’ bipyridyl linkage and/or different oxidation levels of the lycodine units. Complanadines A (1), B (2), D, and E have been reported to induce secretion of neurotrophic factors (NTFs) from 1321N1 human astrocytoma cells, thus they are lead compounds for the development of drugs for treating Alzheimer s disease. Because of their challenging unsymmetrical structures and intriguing biological activities, complanadines have attracted much attention from organic chemists. Two groups reported a total synthesis of complanadine A in 2010. In these pioneering studies, the 2,3’-bipyridyl framework was elegantly constructed, but there are still no reports of efficient and versatile ways of assembling unsymmetrical structures like that of complanadine B (2). Herein, we report the total syntheses of 1 and 2 by straightforward coupling of the monomeric units, which were prepared from a single N-protected lycodine, and the subsequent correction of the reported specific rotation ([a]D) of natural complanadine A (1) to levorotatory. Retrosynthetically, pyridine mono-N-oxide 4 could be a common intermediate for 1 and 2 (Scheme 2). Reduction of 4 would afford 1. Regioselective benzylic oxidation using the

Synthesis of 3-Acyl-2-arylindole via Palladium-catalyzed Isocyanide Insertion and Oxypalladation of Alkyne

The synthesis of 3-acyl-2-arylindole derivatives was performed through palladium-catalyzed isocyanide insertion and oxypalladation of an alkyne. As a result of the introduction of internal nucleophiles, domino cyclization was also achieved for the synthesis of several tetracyclic indole derivatives. Imidoylpalladium generated by isocyanide insertion is a key intermediate in these reactions.

Flexible strategy for syntheses of spirooxindoles using palladium-catalyzed carbosilylation and Sakurai-type cyclization.

The intramolecular carbosilylation of N-[2-(1,3-butenyl)aryl]carbamoyl chloride has been investigated. The reaction with hexamethyldisilane proceeds smoothly in the presence of a catalytic amount of [Pd(η(3)-allyl)Cl](2) to give oxindoles with an allylsilane functional group in good yield. The subsequent subjection of the products to a Sakurai-type reaction provides more advanced tricyclic spirooxindoles by controlling the stereochemistry of three contiguous stereogenic centers.

Asymmetric synthesis of (-)-aurantioclavine via palladium-catalyzed intramolecular allylic amination.

The total synthesis of (-)-aurantioclavine (1) was accomplished based on an intramolecular asymmetric amination of allyl carbonate 3 containing a p-tosylamide group. The reaction using tris(dibenzylideneacetone)dipalladium(0), tBu-phosphinooxazoline, and Bu4NCl in CH2Cl2 gave azepane 2 in 77% yield with 95% enantiomeric excess. The obtained azepane 2 was also converted to a substructure of communesin F.

Synthetic entry to the ABCD ring fragment of gymnocin-A, a cytotoxic marine polyether

Abstract Synthetic entry to the ABCD ring fragment of gymnocin-A, a cytotoxic marine polyether, has been achieved based on the B -alkyl Suzuki–Miyaura coupling-based strategy and radical cyclization for the construction of the tetrahydrofuran ring A.

Asymmetric Synthesis of Trisubstituted Oxazolidinones by the Thiourea-Catalyzed Aldol Reaction of 2-Isocyanatomalonate Diester

A new method has been developed for the synthesis of chiral 4-carboxyl oxazolidinones by the catalytic asymmetric aldol reaction of an isocyanatomalonate diester with an aldehyde in the presence of a thiourea catalyst. The resulting chiral 4-carboxyl oxazolidinones are the equivalent of β-hydroxy-α-amino acids bearing a tri- or tetrasubstituted carbon center at their α position. With this in mind, this procedure was successfully applied to the first total synthesis of mycestericin C, which was completed in 12 steps and represents one of the shortest reported sequences for the construction of natural products of this type.

Total synthesis of (-)-caprazamycin A.

Caprazamycin A has significant antibacterial activity against Mycobacterium tuberculosis (TB). The first total synthesis is herein reported and features a) the scalable preparation of the syn-β-hydroxy amino acid with a thiourea-catalyzed diastereoselective aldol reaction, b) construction of a diazepanone with an unstable fatty-acid side chain, and c) global deprotection with hydrogenation. This report provides a route for the synthesis of related liponucleoside antibiotics with fatty-acid side chains.

Synthetic Approaches to Spiro-oxindoles and Iminoindolines Based on Formation of C2–C3 Bond

Spirooxindole and iminoindoline structures can be found in a wide range of complex natural products, and compounds containing these groups invariably display interesting biological activities. Considering their interesting biological properties and complex architecture, significant research efforts have been directed towards developing new synthetic methods for constructing these structures. This review summarizes our studies towards developing novel synthetic strategies capable of accessing these structures, as well as the applications of these methods to synthesizing natural products, including elacomine and dehaloperophoramidine. CONTENTS 1. Spirooxindole 1-1. Reported Synthetic Methods for Spirooxindole by Forming C2−C3 Bond 1-2. Our Synthetic Strategies 1-3. Construction of Spirooxindole Skeleton by Domino Cyclization 1-4. Formal Synthesis of Elacomine by the Domino Palladium(0)-Catalyzed Spirooxindole Formation 1-5. Synthesis of Spirooxindoles using Silyl Amidation 2. Synthetic Studies on 2-Iminoindoline 2-1. Reported Synthetic Methods for Constructing 2-Iminoindolines and Related Compounds 2-2. SmI2-Mediated Reductive Cyclization of Carbodiimides for Synthesis of Spiro-2-Iminoindolines 2-3. Synthetic Studies of Perophoramidine 3. Summary HETEROCYCLES, Vol. 89, No. 10, 2014 2271