Organic azides are well-known for the synthetic organic reactions by their energetic characteristics and the click functionality connecting two components. Especially in click chemistry, the azido groups as 1,3-dipolar play a key role in chemical biology. On the other hand, azido groups can also work as nucleophiles possessing diazonium leaving groups and as electrophiles, but the low reactivity has avoided their use. Herein, we disclose our synthetic achievements in the non-1,3-dipolar use of organic azides. As nucleophiles, the organic azides with allyl/propargyl cations and sulfonium ions gave the appropriate products, including C-C bond migration. We also demonstrated that the intramolecular hydrogen bonding interaction promoted the electrophilicity and suppressed the nucleophilicity of the azides to achieve site-selective conjugation. Furthermore, β-elimination followed by condensation converted the azido groups at the carbonyl α-position to the different click functional groups. This site-selective azido group conversion enabled the undistinguishable triazide molecule to the distinguishable triple-click scaffold compound possessing three different click groups.
In this account, we describe our studies on transition-metal-catalyzed reactions that efficiently convert C(sp3)-B and C(sp3)-H bonds. In a study of the conversion of C(sp3)-B bonds, we established Suzuki-Miyaura coupling of enantioenriched α-(acylamino)alkylboronic esters with aryl halides. The reaction of α-(pivaloylamino)alkylboronic esters proceeded efficiently under the Pd/XPhos/K2CO3 or Pd/Cy2PPh/CsF catalyst systems to afford enantioenriched alkylamine derivatives with high enantiospecificity. A notable stereochemical course of the reaction was observed: the carbon-carbon bond formation took place with inversion of configuration. In addition, a switch of the stereochemical course was achieved by acidic additives in the reaction of α-(acetylamino)alkylboronic esters. In a study of the conversion of C(sp3)-H bonds, we developed the direct borylation of C(sp3)-H bond of methylsilanes. The reaction proceeded efficiently with bis(pinacolato)diboron and Ir/3,4,7,8-tetramethylphenanthroline (Me4Phen) catalyst to afford (borylmethyl)silanes. The Ir/Me4phen-catalyzed C(sp3)-H borylation of less reactive alkanes, alkyl ethers, and alkylamines was accelerated by adding a catalytic amount of t-BuOK. Based on the efficient C(sp3)-H borylation, conversion of alkyltrimethylsilanes to alkanols was established, which is hard to achieve by Tamao-Fleming oxidation. We also studied catalytic addition of O-methyl and N-methyl C(sp3)-H bond across intramolecular carbon-carbon unsaturated bonds. The reactions of methoxy- and methylaminobenzenes bearing an alkynyl group at the ortho position took place efficiently in the presence of Ir/DTBM-SEGPHOS catalyst to afford benzofurans and indoles. In the reaction of 2-alkenyl-substituted methylamino- and methoxybenzenes with Ir/(S)-DTBM-SEGPHOS catalyst, indolines and 2,3-dihydrobenzofurans having stereogenic carbon center at the C3 position were obtained with high enantiomeric excesses. We also established catalytic dehydrogenation-based molecular transformations. Palladium-catalyzed dehydrogenation of isoindolines to isoindoles and sequential C-H functionalization afforded 1-boryl-, 1-aryl-, and 1-alkynylisoindoles. Iridium-catalyzed cyclization of 2-alkyl-1-(methylamino)benzenes and alkoxybenzenes proceeded through dehydrogenation of the alkyl group and following intramolecular C-H addition to afford N- or O- containing 5-membered rings.
Janus molecules, named after the ancient Roman god of beginnings and doors, generally possess a spatial architecture with dissimilar functional groups on two opposing faces. The existence of structural asymmetry and varied properties in a single molecular unit makes Janus molecules attractive building blocks in materials science. This review centers around the development of Janus structured organic-inorganic hybrid silicon compounds which show great potential in hybrid materials like silane coupling agents, coatings, semiconductors. However, the acquisition of pure Janus silicon molecules is still quite challenging. In this review, we started with the discovery circumstance of the 1st generation of Janus cubes, 3D cubic silsesquioxanes T8. These primary Janus cubes without reactive substituents were firstly observed but not isolated from the transformation of symmetric T8. Later, all-cis cyclic silanols, main precursors for the preparation of well-defined cage-/ladder-type silsesquioxanes, were proved to be efficient starting materials to access Janus silicon compounds. The synthesis of the first isolated Janus cube determined by X-ray structure analysis as well as the 2nd generation of Janus cubes bearing reactive groups (H, OH, vinyl) using cyclic silanols were summarized. Besides, other cage-type Janus siloxanes (Janus prism T6 and Janus lantern cage) obtained from cyclic silanols were briefly described as well. In the last part, we summed up the preparation of various functional groups substituted Janus rings (planar Janus-type cyclotetrasiloxanes) obtained by extension of all-cis cyclic silanols/silanolates, and exhibited the obtention of Janus structured ladder- and bat-siloxanes derived from Janus rings.
Bongkrekic acid (BKA), isolated from the bacterium Burkholderia gladioli, is an inhibitor of adenine nucleotide translocator in the mitochondria inner membrane, and is also a suppressor of apoptosis. Therefore, BKA is an important tool for the investigation of apoptosis as well as mitochondria. Herein, we summarize our total synthesis of BKA and its analogues, and their biological activities. The total synthesis was achieved by employing a three-component convergent strategy based on Julia-Kocienski olefination and Suzuki coupling. Torquoselective olefination with an ynolate was applied for the efficient construction of an unsaturated ester. Based on the total synthesis, various BKA analogues were prepared for structure-activity relationship studies, which indicated that the carboxylic acid moieties were essential for the biological activities of BKA. More readily available BKA analogues with potent biological activity were also developed. A brief summary of the novel biological activities is also provided.
A living cell can be regarded as an ideal machine. To understand the origin of life, it is important to construct a model protocell from a chemical aspect. We have developed a model protocell based on a giant vesicle (GV) in which the self-reproduction of GVs and the replication of their internal DNA proceed in tandem. The success of this linked self-reproduction was attributed to the spontaneous formation of a supramolecular catalyst (C@DNA) consisting of DNA and a protic amphiphile (C), both of which are embedded in the membrane. This model protocell can be viewed as a proliferating supramolecular machine. Furthermore, the frequency and pattern of GV division were found to depend not on the base sequence but on the length of the encapsulated DNA. The C@DNA functions as a lipo-deoxyribosome, and there is a causal relationship between the length of the DNA comprising C@DNA and frequency of protocell proliferation. On the other hand, the newly constructed recursive loop of proliferation consists of four stages: ingestion, replication, maturation, and division, with similarities to the four stages of the living cell cycle. The GV-based model protocells responsible for this soft information flow are sensitive to the environment (starvation time) and exhibit phenotypic plasticity. It was found that a dominant species emerged in an intense competitive proliferation among GVs with DNA of different lengths. This primitive natural selection is a step toward the ultimate goal of model protocells: supramolecular machines that can mimic evolution.
Efficient trifluoromethylation methods would give important approaches for the pharmaceuticals, agrochemicals, materials, and biologically active molecules. In the recent years, notable success was achieved with the development of C(sp3)-H trifluoromethylations, and these reactions have attracted a considerable attention. Herein, recent progress in the field of direct C(sp3)-H trifluoromethylations will be discussed.