Design and Synthesis of a Chiral Halogen-Bond Donor with a Sp3-Hybridized Carbon-Iodine Moiety in a Chiral Fluorobissulfonyl Scaffold.

The first example of a chiral halogen-bond donor with a sp3-hybridized carbon-iodine moiety in a fluorobissulfonyl scaffold is described. The binaphthyl backbone was designed as a chiral source and the chiral halogen-bond donor (R)-1 was synthesized from (R)-1,1'-binaphthol in 11 steps. An NMR titration experiment demonstrated that (R)-1 worked as a halogen-bond donor. The Mukaiyama aldol reaction and quinoline reduction were examined using (R)-1 as a catalyst to evaluate the asymmetric induction.

Trifluoroethoxy-Coated Phthalocyanine Catalyzes Perfluoroalkylation of Alkenes under Visible-Light Irradiation.

We disclose herein the perfluoroalkylation of alkenes catalyzed by trifluoroethoxy-coated zinc phthalocyanine under irradiation of visible light. Perfluoroalkyl iodides were nicely incorporated into unsaturated substrates, including alkyne, to provide perfluoroalkyl and iodide adducts in moderate to good yields. Trifluoromethylation is also possible by trifluoromethyl iodide under the same reaction conditions. The mechanistic study is discussed.

IF5 affects the final stage of the Cl-F exchange fluorination in the synthesis of pentafluoro-λ6-sulfanyl-pyridines, pyrimidines and benzenes with electron-withdrawing substituents.

A difficult chlorine-fluorine (Cl-F) exchange fluorination reaction in the final stage of the preparation of pentafluoro-λ6-sulfanyl-(hetero)arenes having electron-withdrawing substituents has now been elucidated through the use of iodine pentafluoride. A major side-reaction of C-S bond cleavage was sufficiently inhibited by the potential interaction between F and I with a halogen bonding.

Trifluoroethoxy-Coated Subphthalocyanine affects Trifluoromethylation of Alkenes and Alkynes even under Low-Energy Red-Light Irradiation.

Photoredox chemical reactions induced by visible light have undergone a renaissance in recent years. Polypyridyl dyes such as Ir(ppy)3 and Ru(bpy)3 are key catalysts in this event, and blue- or white-light irradiation is required for the chemical transformations. However, it remains a challenge to achieve reactions under the lower energy of red light. We disclose, herein, that trifluoroethoxy-coated subphthalocyanine realizes the red-light-driven trifluoromethylation of alkenes and alkynes with trifluoromethyl iodide in good-to-high yields. Perfluoroalkylations were also achieved under red light. The reaction mechanism is discussed with the support of UV/Vis spectroscopy and cyclic voltammetry of trifluoroethoxy-coated subphthalocyanine. Light irradiation/dark study also supports the proposed mechanism.

SF5-Pyridylaryl-λ3-iodonium salts and their utility as electrophilic reagents to access SF5-pyridine derivatives in the late-stage of synthesis.

Electrophilic pentafluorosulfanyl (SF5) heteroarylation of target molecules using novel reagents is described. Unsymmetrical diaryliodonium reagents 1 having 2-SF5-pyridine have been synthesized in good yields. They are efficient electrophilic reagents for carbon and heterocentered nucleophiles, producing the corresponding SF5-pyridine derivatives in good to excellent yields.

Corrigendum: Sterically Demanding Unsymmetrical Diaryl-λ(3)-iodanes for Electrophilic Pentafluorophenylation and an Approach to α-Pentafluorophenyl Carbonyl Compounds with an All-Carbon Stereocenter.

[This corrects the article DOI: 10.1002/open.201402045.].

Importance of a Fluorine Substituent for the Preparation of meta- and para-Pentafluoro-λ(6) -sulfanyl-Substituted Pyridines.

Although there are ways to synthesize ortho-pentafluoro-λ(6) -sulfanyl (SF5 ) pyridines, meta- and para-SF5 -substituted pyridines are rare. We disclose herein a general route for their synthesis. The fundamental synthetic approach is the same as reported methods for ortho-SF5 -substituted pyridines and SF5 -substituted arenes, that is, oxidative chlorotetrafluorination of the corresponding disulfides to give pyridylsulfur chlorotetrafluorides (SF4 Cl-pyridines), followed by chloride/fluoride exchange with fluorides. However, the trick in this case is the presence on the pyridine ring of at least one fluorine atom, which is essential for the successful transformation of the disulfides into m-and p-SF5 -pyridines. After enabling the synthesis of an SF5 -substituted pyridine, ortho-F groups can be efficiently substituted by C, N, S, and O nucleophiles through an SN Ar pathway. This methodology provides access to a variety of previously unavailable SF5 -substituted pyridine building blocks.

Constitutive Activation of PINK1 Protein Leads to Proteasome-mediated and Non-apoptotic Cell Death Independently of Mitochondrial Autophagy.

Phosphatase and tensin homolog-induced putative kinase 1 (PINK1), a Ser/Thr kinase, and PARKIN, a ubiquitin ligase, are causal genes for autosomal recessive early-onset parkinsonism. Multiple lines of evidence indicate that PINK1 and PARKIN cooperatively control the quality of the mitochondrial population via selective degradation of damaged mitochondria by autophagy. Here, we report that PINK1 and PARKIN induce cell death with a 12-h delay after mitochondrial depolarization, which differs from the time profile of selective autophagy of mitochondria. This type of cell death exhibited definite morphologic features such as plasma membrane rupture, was insensitive to a pan-caspase inhibitor, and did not involve mitochondrial permeability transition. Expression of a constitutively active form of PINK1 caused cell death in the presence of a pan-caspase inhibitor, irrespective of the mitochondrial membrane potential. PINK1-mediated cell death depended on the activities of PARKIN and proteasomes, but it was not affected by disruption of the genes required for autophagy. Furthermore, fluorescence and electron microscopic analyses revealed that mitochondria were still retained in the dead cells, indicating that PINK1-mediated cell death is not caused by mitochondrial loss. Our findings suggest that PINK1 and PARKIN play critical roles in selective cell death in which damaged mitochondria are retained, independent of mitochondrial autophagy.

Synthesis of Diaryliodonium Salts Having Pentafluorosulfanylarenes and Their Application to Electrophilic Pentafluorosulfanylarylation of C-, O-, N-, and S-Nucleophiles.

Novel reagents for the electrophilic introduction of pentafluorosulfanyl (SF5) arenes into target molecules are disclosed. Unsymmetrical diaryliodonium salts 1 having SF5-arenes were synthesized by a one-pot process from iodo-SF5-benzenes 2 in good yields. The SF5-aryliodonium salts 1 were found to be efficient for the electrophilic SF5-arylation of carbon and heterocentered nucleophiles to furnish the corresponding substituted SF5-arenes in good to high yields.

Sterically Demanding Unsymmetrical Diaryl-λ(3)-iodanes for Electrophilic Pentafluorophenylation and an Approach to α-Pentafluorophenyl Carbonyl Compounds with an All-Carbon Stereocenter.

A sterically demanding unsymmetrical pentafluorophenyl-triisopropylphenyl-λ(3)-iodane was developed as an effective reagent for the electrophilic pentafluorophenylation of various ß-keto esters and a ß-keto amide. 17 examples of α-pentafluorophenylated 1,3-dicarbonyl compounds 3 having a quaternary carbon center are provided. The resulting compounds were nicely transformed into chiral α-pentafluorophenyl ketones with an all-carbon stereogenic center in high yields and high enantioselectivities using asymmetric organocatalysis (up to 98 % ee) or asymmetric metal catalysis (up to 82 % ee).

Enantioselective monofluoromethylation of aldehydes with 2-fluoro-1,3-benzodithiole-1,1,3,3-tetraoxide catalyzed by a bifunctional cinchona alkaloid-derived thiourea-titanium complex.

A catalytic enantioselective monofluoromethylation of aldehydes using 2-fluoro-1,3-benzodithiole-1,1,3,3-tetraoxide (FBDT) was realized. With a bifunctional thiourea-titanium catalytic system, the monofluoromethylated-adducts were obtained in good yields and high enantioselectivities, up to 96% ee.

Highly enantioselective monofluoromethylation of C2-arylindoles using FBSM under chiral phase-transfer catalysis.

The highly enantioselective addition of 1-fluoro-1,1-bis(phenylsulfonyl)methane (FBSM) to vinylogous imines generated in situ from 2-aryl-3-(1-arylsulfonylmethyl)indoles was achieved using chiral ammonium salts derived from cinchona alkaloids. One-pot conversion from 2-arylindoles with FBSM was also adaptable under the same reaction conditions. The key for this transformation is the effective use of the arylsulfonyl group.