Brønsted acid-catalyzed synthesis of spirocyclobutanes via heteroannulation of vinyloxyphenylbicyclobutanes with water.

We report a perchloric acid-catalyzed heteroannulation for the synthesis of spirocyclobutanes using vinyloxyphenylbicyclobutanes with water. This metal-free reaction yields high product outputs and is consistent with the formation of a cyclobutene intermediate originating from an isomerization of a bicyclobutane.

Axially Chiral Borinic Acid Catalysts: Design, Synthesis, and Application in Alkylative Desymmetrization of 1,2-Diols.

A novel chiral borinic acid (CBA), an organocatalyst possessing a binaphthyl skeleton, was designed and synthesized. The synthesis of CBA was achieved with a 72% yield in four steps starting with optically pure 1,1'-bi-2-naphthol. The asymmetric catalytic activity was investigated in the desymmetrization of meso-1,2-diol.

Palladium-Catalyzed Intramolecular Migratory Cycloisomerization of 3-Phenoxy Acrylic Acid Ester via C-O Bond Cleavage and C-O/C-C Bonds Formation for 2,3-Disubstituted Benzofurans Synthesis.

Migratory cycloisomerization using transition metal catalyst is useful for synthesizing substituted heterocyclic compounds. We achieved palladium-catalyzed migratory cycloisomerization of 3-o-alkynylphenoxy acrylic acid ester derivatives to give 2,3-disubstituted benzofurans. Although there are several reports of benzofuran synthesis with palladium-catalyzed migratory cycloisomerization, migratory groups are limited to allyl and propargyl groups. This report is the first example of benzofuran synthesis with palladium-catalyzed cycloisomerization of C(sp2)-O bond cleavage.

Double Ring Expansion Strategy for Fused 3-Benzazepines: Alternative Synthesis of the Dolby-Weinreb Enamine.

A double ring expansion strategy for constructing fused 3-benzazepines is described. The oxidative ring expansion of spiroamine compounds with N-chlorosuccinimide and subsequent ring expansion of the resulting ketiminium ion intermediates with trimethylsilyldiazomethane afforded fused 3-benzazepines in a one-pot operation. Importantly, the Dolby-Weinreb enamine, which is a key synthetic intermediate for harringtonine alkaloids, cephalotaxines, can be accessed from commercial materials in only two steps using our developed method.

Total Synthesis of Ansellone G and Phorbadione.

The first total synthesis of marine sesterterpenoid ansellone G (2) was accomplished. This strategy utilizes the Prins cyclization reaction of a chloro-substituted homoallyl alcohol to synthesize the hydrobenzopyran skeleton. The preintroduction of the chloro groups facilitated the functional group transformation for 2 after constructing the carbon framework. Furthermore, we also successfully synthesized phorbadione (3) by dehydrating the tertiary alcohol. The HIV latency-reversing activity of the synthesized 2, 3, and deacetylated 2 was also evaluated.

Chiral Dinuclear Vanadium Complex-Mediated Oxidative Coupling of Resorcinols.

A method for the highly regio- and enantioselective oxidative coupling of resorcinols has been established by using dibrominated dinuclear vanadium(V) catalyst 1c under air. When resorcinols bearing an aryl substituent were applied as substrates to the coupling, axially chiral biresorcinols were obtained as single regioisomers in high yield with up to 98% ee.

Asymmetric oxidative coupling of hydroxycarbazoles: Facile synthesis of (+)-bi-2-hydroxy-3-methylcarbazole.

Asymmetric oxidative coupling reactions of hydroxycarbazoles have been established using a chiral dinuclear vanadium complex. To demonstrate the utility of vanadium-catalyzed reactions, we have used them to synthesize (+)-bi-2-hydroxy-3-carbazole in three steps from cyclohexanone and commercially available aniline derivatives.

Chiral Organocatalyzed Intermolecular Rauhut-Currier Reaction of Nitroalkenes with Ethyl Allenoate.

An enantioselective intermolecular Rauhut-Currier (RC) reaction of nitroalkenes with ethyl allenoate has been established with quinidine-derived ß-isocupreidine. The present RC reaction afforded α-functionalized allenoates 3 in up to 94% yield with 59% enantiomeric excess (ee).

Efficient Enantioselective Synthesis of Oxahelicenes Using Redox/Acid Cooperative Catalysts.

An efficient and enantioselective synthesis of oxa[9]helicenes has been established via vanadium(V)-catalyzed oxidative coupling/intramolecular cyclization of polycyclic phenols. A newly developed vanadium complex cooperatively functions as both a redox and Lewis acid catalyst to promote the present sequential reaction and afford oxa[9]helicenes in good yields with up to 94% ee.

Asymmetric Brønsted Acid Catalyzed Substitution of Diaryl Methanols with Thiols and Alcohols for the Synthesis of Chiral Thioethers and Ethers.

An enantioselective addition of thiols and alcohols to aza-ortho-quinone methides, starting from diaryl methanols, was developed. The asymmetric additions occur under mild reaction conditions in the presence of chiral phosphoric acids and furnish the corresponding adducts with excellent yields and enantioselectivities.

An enantioselective organocatalyzed aza-Morita-Baylis-Hillman reaction of isatin-derived ketimines with acrolein.

A highly enantioselective aza-Morita-Baylis-Hillman (aza-MBH) reaction of isatin-derived ketimines with acrolein was established using ß-isocupreidine (ß-ICD) or α-isocupreine (α-ICPN) as a chiral acid-base organocatalyst. The present protocol readily furnished (S) or (R)-aza-MBH adducts with a chiral tetrasubstituted carbon stereogenic center in up to 98% ee.

Heteroannulation of bicyclobutane derivatives via Au-catalyzed hydration to enol ethers and intramolecular cyclization giving spirocyclobutanes.

We report the heteroannulations of bicyclobutane derivatives bearing enol ether groups in the presence of H2O under mild conditions. The reaction affords spirocyclobutanes with cyclic acetal groups via the Au-catalyzed hydration of the enol ether group and subsequent intramolecular cyclization.

Double isomerization/cycloisomerization/aromatization of 1-(allyloxy)-2-(cyclopropylmethyl)benzenes to give 2-ethyl-3-isopropylbenzofurans using a multitasking single rhodium catalyst.

Multitasking single-catalyst systems that allow multiple chemical transformations within a single reaction vessel are important for the development of eco-compatible chemistry. Here, we have developed a rhodium-catalyzed system that transforms 1-(allyloxy)-2-(cyclopropylmethyl)benzene derivatives to 2-ethyl-3-isopropylbenzofurans via double isomerization/cycloisomerization/aromatization.

Electrochemical synthesis of heterodehydro[7]helicenes.

Dehydrohelicenes are some of the most attractive chiroptical materials with unique helical chirality. However, to our knowledge, there are no prior reports on their direct construction by asymmetric methods. In this work, sequential synthesis of aza-oxa-dehydro[7]helicenes via the electrochemical oxidative hetero-coupling of 3-hydoxycarbazoles and 2-naphthols followed by dehydrative cyclization and intramolecular C-C bond formation has been realized. In addition, an efficient enantioselective synthesis through chiral vanadium-catalyzed hetero-coupling and electrochemical oxidative transformations afforded heterodehydro[7]helicene without any racemization. The obtained dehydro[7]helicenes showed intense blue-colored circularly polarized luminescence (|glum| ≈ 2.5 × 10-3 at 433 nm). Thermodynamic and kinetic studies of the racemization barrier of heterodehydro[7]helicenes indicated significant chiral stability with ΔG‡> 140 kJ mol-1.

Design, Synthesis, and Monoamine Oxidase B Selective Inhibitory Activity of N-Arylated Heliamine Analogues.

Monoamine oxidase B (MAO-B) metabolizes monoamines such as dopamine regarding neural transmission and controls its level in the mammalian's brain. When MAO-B metabolizes dopamine abnormally, normal neurotransmission does not occur, and central nervous system disorders such as Parkinson's disease may develop. Although several MAO inhibitors have been developed, most of them have no selectivity between monoamine oxidase A (MAO-A) and MAO-B, or they work irreversibly against the enzyme. This report describes the first case of screening of N-arylated heliamine derivatives to develop novel MAO-B selective inhibitors that can be synthesized concisely by microwave-assisted Pd nanoparticle-catalyzed Buchwald-Hartwig amination. We discovered that the derivatives 4h, 4i, and 4j display inhibitory activity against MAO-B with IC50 values of 1.55, 13.5, and 5.08 µM, respectively.

Iridium-Catalyzed Isomerization/Cycloisomerization/Aromatization of N-Allyl-N-sulfonyl-o-(λ1-silylethynyl)aniline Derivatives to Give Substituted Indole Derivatives.

We have developed a one-iridium-catalyst system that transforms N-allyl-N-sulfonyl-2-(silylalkynyl)aniline derivatives, which are 1,7-enynes in which both multiple bonds have a heteroatom, to the corresponding substituted indole derivatives via isomerization/cycloisomerization/aromatization. This strategy provides an atom-economical and straightforward synthetic approach to a series of valuable indoles having vinyl and silylmethyl groups at the 2- and 3-positions.

Chemo- and regioselective cross-dehydrogenative coupling reaction of 3-hydroxycarbazoles with arenols catalyzed by a mesoporous silica-supported oxovanadium.

Cross-dehydrogenative coupling between 3-hydroxycarbazoles and 2-naphthols has been achieved by using a mesoporous silica-supported oxovanadium catalyst.

Catalytic and enantioselective oxa-Piancatelli reaction using a chiral vanadium complex.

An enantioselective oxa-Piancatelli reaction was established for the first time using a chiral vanadium(v) catalyst. The dual Brønsted and Lewis acid properties of the vanadium catalyst afforded 4-hydroxycyclopent-2-enone derivatives in up to 90% yields and with 93 : 7 enantiomeric ratios, as well as >20 : 1 diastereomeric ratios.

Correction: Exploration of flow reaction conditions using machine-learning for enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence.

Correction for 'Exploration of flow reaction conditions using machine-learning for enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence' by Masaru Kondo et al., Chem. Commun., 2020, 56, 1259-1262, DOI: 10.1039/C9CC08526B.

Exploration of flow reaction conditions using machine-learning for enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence.

A highly atom-economical enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence has been established by using a flow system. Suitable flow conditions were explored through reaction screening of multiple parameters using machine learning. Eventually, functionalized chiral spirooxindole analogues were obtained in high yield with good ee as a single diastereomer within one minute.