Ikuo Sasaki

Aromatic C–H silylation of arenes with 1-hydrosilatrane catalyzed by an iridium(I)/2,9-dimethylphenanthroline (dmphen) complex

Aromatic C-H silylation of neat arenes with 1-hydrosilatrane was found to be efficiently catalyzed by iridium catalysts composed of 1/2[Ir(OMe)(cod)]2 and 2,9-dimethyl-1,10-phenanthroline at 120 °C to afford the corresponding silylated products in high yields. The silylated products can be used for the Hiyama cross-coupling reaction.

A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin

Peptide antibiotics are typically biosynthesized by one of two distinct machineries in a ribosome-dependent or ribosome-independent manner. Pheganomycin (PGM (1)) and related analogs consist of the nonproteinogenic amino acid (S)-2-(3,5-dihydroxy-4-hydroxymethyl)phenyl-2-guanidinoacetic acid (2) and a proteinogenic core peptide, making their origin uncertain. We report the identification of the biosynthetic gene cluster from Streptomyces cirratus responsible for PGM production. Unexpectedly, the cluster contains a gene encoding multiple precursor peptides along with several genes plausibly encoding enzymes for the synthesis of amino acid 2. We identified PGM1, which has an ATP-grasp domain, as potentially capable of linking the precursor peptides with 2, and validate this hypothesis using deletion mutants and in vitro reconstitution. We document PGM1s substrate permissivity, which could be rationalized by a large binding pocket as confirmed via structural and mutagenesis experiments. This is to our knowledge the first example of cooperative peptide synthesis achieved by ribosomes and peptide ligases using a peptide nucleophile.

Iridium(I)-catalyzed vinylic C–H borylation of 1-cycloalkenecarboxylates with bis(pinacolato)diboron

Ir(I)-catalyzed C-H borylation of 1-cycloalkenecarboxylic derivatives with bis(pinacolato)diboron affords various alkenylboronates with functional groups in excellent yields. This reaction was also used in a one-pot borylation/Suzuki-Miyaura cross-coupling procedure.

Iridium-catalyzed ortho-C–H borylation of aromatic aldimines derived from pentafluoroaniline with bis(pinacolate)diboron

The development of an Ir-catalyzed ortho-C-H borylation of aromatic aldimines derived from pentafluoroaniline is reported. This reaction proceeded at 120 °C to afford the corresponding borylated products in high yield with good regioselectivity using an Ir complex formed in situ from [Ir(OMe)(cod)]2/2(C6F5)3P in the presence of 2-norbornene.

Synthesis of Acylborons by Ozonolysis of Alkenylboronates: Preparation of an Enantioenriched Amino Acid Acylboronate

A concise synthesis of acylborons was achieved by ozonolysis of alkenyl MIDA (N-methyliminodiacetic acid) boronates. This reaction exhibits excellent functional-group tolerance and is applicable to various acyl MIDA boronates and potassium acyltrifluroborates (KATs) which could not be synthesized by previous methods. In addition, α-amino acylborons, which would be essential for peptide ligations, were prepared for the first time. The acylboron of l-alanine was obtained in high enantiopurity and found to be configurationally stable. Oligopeptide synthesis between the α-amino KATs and amino acid in dilute aqueous media was studied.

Iridium(I)-catalyzed C-H Borylation of α,β-Unsaturated Esters with Bis(pinacolato)diboron.

A new process has been developed for the iridium(I)-catalyzed vinylic C-H borylation of α,β-unsaturated esters with bis(pinacolato)diboron (B2 pin2 ). These reactions proceeded in octane at temperatures in the range of 80-120 °C to afford the corresponding alkenylboronic compounds in high yields with excellent regio- and stereoselectivities. The presence of an aryl ester led to significant improvements in the yields of the acyclic alkenylboronates. Crossover experiments involving deuterated substrates as well as a mixture of stereoisomers confirmed that this reaction proceeds via a 1,4-addition/β-hydride elimination mechanism. Notably, this reaction was also used to develop a one-pot borylation/Suzuki-Miyaura cross-coupling procedure.

Synthesis of 1,2,3-Triazines Using the Base-Mediated Cyclization of (Z)-2,4-Diazido-2-alkenoates

A highly efficient and convenient method for the synthesis of 6-aryl-1,2,3-triazine-4-carboxylate esters has been developed using readily accessible ( Z)-4-aryl-2,4-diazido-2-alkenoates. This reaction is performed under mildly basic conditions without the assistance of any transition metals or strong acid.

Total Synthesis of (+)-Pyrenolide D

An efficient approach to stereoselective construction of a spiro-γ-lactone core structure via BF3-promoted formal [3 + 2] annulation of aldehydo-aldose derivatives with γ-methylene-γ-butyrolactone has been developed. The spiro-γ-lactone derivative was then used in an efficient total synthesis of (+)-pyrenolide D. The developed chemistry paves the way for total synthesis of structurally diverse natural products containing spiro-lactone cores.