Takeshi Nanjo

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.

Amide-containing molecules are ubiquitous in natural products, pharmaceuticals, and materials science. Due to their intermediate electron-richness, they are not amenable to any of the previously developed N-protection strategies known to enable remote aliphatic C-H oxidations. Using information gleaned from a systematic study of the main features that makes remote oxidations of amides in peptide settings possible, we developed an imidate salt protecting strategy that employs methyl trifluorometh

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.

We report a pyridine-based donor–acceptor molecule that exhibits high reactivity as a visible-light photoredox catalyst. This photoredox catalyst enables the formation of radicals from alkyl bromides, which are useful radical precursors that unfortunately do not perform well under reductive conditions, by a direct, photocatalytic reductive cleavage of the C–Br bond. A wide variety of alkyl bromides including unactivated ones can be used under ambient conditions without any additional activating

The homolytic cleavage of C-O bonds to afford alkyl radicals is an attractive yet challenging transformation in organic synthesis. Herein we describe a photocatalyzed deoxygenative C-C coupling reaction of xanthate salts, which can be easily prepared from the corresponding alcohols. The key to the success of this strategy is the low oxidation potential of the xanthate salt and the use of an appropriate phosphine to accelerate the desulfurative release of carbonyl sulfide.

The catalytic enantioselective addition of glyoxylate cyanohydrin to imines to afford α-keto-β-amino acid equivalents is reported. Sterically tuned aminobenzothiadiazine catalysts provided high yields and stereoselectivities (up to 100% yield, 99% ee, >99:1 dr) for both aromatic and aliphatic imines, and the stereodivergent synthesis of both diastereomers was achieved. The optimal catalytic system was scalable, even with a low catalyst loading. The resulting adducts were converted into various c

Strategies for the formation of amide bonds, that is, one of the most basic and important transformations in organic synthesis, have so far focused predominantly on dehydration reactions. Herein, we report and demonstrate the practical utility of a novel decarboxylative amidation of α-ketoacids by using inexpensive tert-butyl hydroperoxide (TBHP), which is characterized by high yields, a broad substrate scope, mild reaction conditions, and a unique chemoselectivity. These features enable the syn

An α-ketoacid could be converted into a reactive acylating agent by treatment with hypervalent iodine(III) species, and in so doing, we discovered a novel decarboxylative acylation of alcohols that affords a variety of esters in excellent yields. The esterification has been applied to a sterol bearing a free carboxylic acid and shows unique chemoselectivity. The procedure is racemization-free and operates under mild conditions.

The synthesis of benzocyclobutenes from simple arenes bearing a directing group was investigated via the palladium-catalyzed cyclization of norbornene derivatives. This approach allowed for the facile construction of benzocyclobutenes along with the double functionalization of the C-H bonds at the positions ortho and meta to the directing group. This result shows that the key palladacyclopentene intermediate in the Catellani reaction can be prepared by the directed double ortho C-H activation of

β-Amino-α-ketoacids are important unnatural amino acids that exhibit unique bioactivity and reactivity derived from the highly electrophilic carbonyl group at the α-position. Despite the broad utility of the motif, reliable synthetic methods for β-amino-α-ketoacids have been limited to the oxidative homologation of α-amino acids based on a chiral-pool approach. In this article, we report an alternative practical method for the asymmetric synthesis of β-amino-α-ketoacid equivalents based on a hig

Abstract Conventional methods for the construction of dehydroamino acids (ΔAAs), which are a unique class of non‐proteinogenic amino acids, require the pre‐installation of special amino acids. Herein, we report and demonstrate the practical utility of an N ‐chloropeptide strategy for the rapid construction of ΔAA‐containing peptides. The electrophilic N ‐chlorination of peptide bonds is drastically accelerated by a catalytic amount of quinuclidine (ABCO), and the subsequent β‐elimination of N ‐c

Synthesis of 3,3-disubstituted 2-aminoindolenines was achieved by palladium-catalyzed allylic amidination with an isocyanide. It was found that isocyanides are effective building blocks in palladium-catalyzed allylic functionalizations, analogous to carbon monoxide. This approach enables the direct construction of the indolenine ring along with the formation of a quaternary carbon and the introduction of an amino substituent in one step under mild conditions.

The introduction of a chlorine atom could potentially endow peptide derivatives with notable bioactivity and applicability. However, despite considerable recent progress in C(sp³)-H functionalization chemistry, a general method for the site-selective chlorination of inert aliphatic C-H bonds in peptides still remains elusive. Herein, we report a site-selective C(sp³)-H chlorination of oligopeptides based on an <i>N</i>-chloropeptide strategy. <i>N</i>-chloropeptides, which

Abstract In this article, we describe the stereoselective formation of β,β‐disubstituted dehydroamino acids (ΔAAs) in peptides using a cationic rhodium catalyst and methyl trifluoroborate salt. Using this approach, an alkyl group was directly installed on a β‐monosubstituted ΔAA in the peptide chain and both isomers of dehydroisoleucine, an important yet usually inaccessible ΔAA, were successfully obtained.

We here report the use of a sterically tuned 2-fluoro-1-methylpyridinium salt for the catalyst-free, visible-light-mediated deoxygenative transformation of alcohols through alkoxypyridinium intermediates. The key to this process is the introduction of a bulky cyclohexyl group at the 3-position of the pyridinium ring, which enforces a favorable conformation for C-O bond cleavage and the formation of an electron donor-acceptor complex between the pyridinium ring and amines.