Synthesis of trans-Tetrafluoro(trifluoromethyl)-λ⁶-sulfanyl (CF₃SF₄)-Containing Olefins via Cross Metathesis

Zhao X., Shou J., Newton J.J., Qing F.

trans-Trifluoromethyltetrafluorosulfanyl chloride (trans-CF3SF4Cl) is a unique reagent for the incorporation of the CF3SF4 group into organic compounds. However, CF3SF4Cl was prepared from hazardous reagents or formed as mixture of trans and cis isomers in low yield. Herein, a silver-promoted selective synthesis of trans-CF3SF4Cl under safe gas-reagent-free conditions is described. Furthermore, the synthetic application of trans-CF3SF4Cl is demonstrated through the new trifluoromethyltetrafluorosulfanylation of α-diazo carbonyl compounds.

Abera Tsedalu A.

Olefin metathesis is a metal-mediated C-C bond exchange by which the two fragments within the olefin precursor are redistributed as a result of breaking the double bond to obtain a new product. Currently, most of the synthetic organic compounds, polymers, drugs, plastics, and other synthetic materials are synthesized via the application of olefin metathesis reactions. In this review, different types of olefin metathesis reactions with their plausible mechanisms and their application in synthetic organic chemistry have been discussed.

Sarmento Fernandes L., Mandelli D., Carvalho W.A., Caytan E., Fischmeister C., Bruneau C.

• Cross metathesis of bio-sourced sterically hindered cyclic terpenes and terpenoids with internal (functional) olefins. • Ruthenium-catalyzed olefin metathesis. • Green chemistry: catalytic transformations of abundant natural products. • High regio- and stereoselectivity. The straightforward functionalization of sterically demanding α,α-disubstituted double bonds of β-pinene, (-)-limonene and (-)-limonene terpenoids has been achieved via cross metathesis with internal olefins. The reactions are catalyzed by second generation ruthenium catalysts in dimethyl carbonate as green solvent or under neat conditions. This transformation provides a clean process for the access to functionalized bulky cyclic terpenes where the terminal double bond generates a trisubstituted olefin.

Matsuo T.

Hoveyda–Grubbs-type complexes, ruthenium catalysts for olefin metathesis, have gained increased interest as a research target in the interdisciplinary research fields of chemistry and biology because of their high functional group selectivity in olefin metathesis reactions and stabilities in aqueous media. This review article introduces the application of designed Hoveyda–Grubbs-type complexes for bio-relevant studies including the construction of hybrid olefin metathesis biocatalysts and the development of in-vivo olefin metathesis reactions. As a noticeable issue in the employment of Hoveyda–Grubbs-type complexes in aqueous media, the influence of water on the catalytic activities of the complexes and strategies to overcome the problems resulting from the water effects are also discussed. In connection to the structural effects of protein structures on the reactivities of Hoveyda–Grubbs-type complexes included in the protein, the regulation of metathesis activities through second-coordination sphere effect is presented, demonstrating that the reactivities of Hoveyda–Grubbs-type complexes are controllable by the structural modification of the complexes at outer-sphere parts. Finally, as a new-type reaction based on the ruthenium-olefin specific interaction, a recent finding on the ruthenium complex transfer reaction between Hoveyda–Grubbs-type complexes and biomolecules is introduced.

Tobón P., Gómez S., Restrepo A., Núñez-Zarur F.

Quantum mechanical calculations on the mechanism of olefin metathesis with a variety of substituents mediated by a Ru alkylidene catalyst reveal multistep processes along the general reactants → ad...

Ikeda A., Capellan A., Welch J.T.

The polar hydrophobic trifluoromethyl-λ6-tetrafluorosulfanyl (CF3SF4) group effectively induces secondary structure in a heptapeptide in both polar and non-polar solvents.

Schowner R., Elser I., Toth F., Robe E., Frey W., Buchmeiser M.R.

An extensive series of the first ionic Mo- and W-based Schrock-type catalysts based on pyridinium and phosphonium tagged aryloxide ligands were prepared. Bisionic complexes of the general formula Mo(Imido)(CHR)(OR')2 (OTf)2 and monoionic monoaryloxide pyrrolide (pyr) (MAP-type) catalysts [M(Imido)(CHR)(OR')(pyr)+ ][A- ] were successfully employed and tested in various olefin metathesis benchmark reactions under both, homogeneous and biphasic conditions using pyrrole and, for the first time with Schrock-type catalysts, ionic liquids as the polar phase. Productivities under biphasic conditions up to several thousand turn overs were achieved and are comparable to those obtained in reactions carried out in chlorobenzene or toluene. Metal contamination in the nonpolar product-containing heptane phase was

Ikeda A., Zhong L., Savoie P.R., von Hahmann C.N., Zheng W., Welch J.T.

Trichloromethanesulfenyl chloride was conveniently converted to trans-trifluoromethyl tetrafluoro-λ6-sulfanyl chloride (CF3SF4Cl) by oxidative chlorofluorination. Triethylborane-promoted addition reactions of trans-CF3SF4Cl to substituted olefins and alkynes yielded a variety of new materials. Those addition products were subsequently transformed to CF3SF4-substituted carboxylic acids, ketones, and an aldehyde.

Elser I., Schowner R., Frey W., Buchmeiser M.R.

Ionic Mo- and W-imido alkylidene N-heterocyclic carbene (NHC) olefin metathesis catalysts, [Mo{N-2,6-(Me2 )C6 H3 }(CHCMe2 Ph)(IMesH2 )(OTf)(PPS)]OTf (3), [Mo(N-2,6-(Me2 )C6 H3 )(CHCMe2 Ph)(IMesH2 )(OC6 F5 )(PPS)][B(ArF )4 ] (5), [Mo(NtBu)(CHCMe2 Ph)(4,5-dichloro-1,3-dimethylimidazol-2-ylidene)(OTf)(2,6-Ph-4-{2,4,6-Ph-pyridinium}phenolate)][OTf] (9), [Mo(NtBu)(CHCMe2 Ph)(4,5-dichloro-1,3-dimethylimidazol-2-ylidene)(2,6-Ph-4-{2,4,6-Ph-pyridinium}phenolate)][B(ArF )4 ]2 (10, PPS=pyridiniumpropanesulfonate, IMesH2 =1,3-dimesitylimidazolin-2-ylidene, OTf=CF3 SO3 , B(ArF )4 =tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) were prepared from betaine-type ligands. Also, the first bis-NHC and a nitron-based bis(amido) bistriflate imido alkylidene complex, [Mo(NtBu)(CHCMe2 Ph)(4,5-dichloro-1,3-dimethylimidazol-2-ylidene)2 (THF)(2,6-Ph-4-{2,4,6-Ph-pyridinium}phenolate)][OTf]2 (11) and [Mo(N-2,6-Me2 -C6 H3 )(CHCMe2 Ph)(N-{1,4-diphenyl-1,3,4-triazol-2-ylium}-N-phenyl-amido)2 ][OTf]2 (14) along with ionic [W(N-2,6-iPr2 -C6 H3 )(CHCMe2 Ph)(N-2,5-Me2 C4 H2 )(IiPr)(2,6-tBu-4-PPh3 -phenolate)] (17, IiPr=1,3-diisopropylimidazol-2-ylidene) are reported. With these new catalysts, the first biphasic reaction setup with Group 6 metal alkylidene NHC complexes was successfully established using a pyrrole/heptane mixture as a liquid phase. Productivities under biphasic conditions were comparable to those of reactions in 1,2-dichloroethane or toluene. Metal concentrations of

Herbert M.B., Grubbs R.H.

Olefin cross metathesis is a particularly powerful transformation that has been exploited extensively for the formation of complex products. Until recently, however, constructing Z-olefins using this methodology was not possible. With the discovery and development of three families of ruthenium-based Z-selective catalysts, the formation of Z-olefins using metathesis is now not only possible but becoming increasingly prevalent in the literature. In particular, ruthenium complexes containing cyclometalated NHC architectures developed in our group have been shown to catalyze various cross metathesis reactions with high activity and, in most cases, near perfect selectivity for the Z-isomer. The types of cross metathesis reactions investigated thus far are presented here and explored in depth.

Yoshida K.

Modern synthetic organic chemistry has sufficient flexibility to construct acyclic compounds selectively rather than aromatic compounds. Therefore, the direct construction of aromatic rings from acyclic precursors would provide one possible solution to the difficulty of responding to the growing demand for complex aromatic compounds. Combinations of the cyclization of acyclic precursors prepared in a selective manner and subsequent aromatization provide effective means to access the aromatic compounds desired without the formation of inseparable regioisomers. This chapter presents representative synthetic examples of aromatic compounds using ring-closing metathesis (RCM), divided into several types of methods. The chapter discusses methods such as alkene metathesis, and ene—yne metathesis. Since RCM has become one of the most powerful cyclization reactions, great possibilities can be expected in this field.

Kramer J.R., Deming T.J.

Conformation-switchable glycopolypeptides were prepared by the living polymerization of glycosylated L-cysteine-N-carboxyanhydride (glyco-C NCA) monomers. These new monomers were prepared in high yield by coupling of alkene-terminated C-linked glycosides of D-galactose or D-glucose to L-cysteine using thiol-ene "click" chemistry, followed by their conversion to the corresponding glyco-C NCAs. The resulting glycopolypeptides were found to be water-soluble and α-helical in solution. Aqueous oxidation of the side-chain thioether linkages in these polymers to sulfone groups resulted in disruption of the α-helical conformations without loss of water solubility. The ability to switch chain conformation and remain water-soluble is unprecedented in synthetic polymers, and allows new capabilities to control presentation of sugar functionality in subtly different contexts.

Keitz B.K., Endo K., Herbert M.B., Grubbs R.H.

The cross-metathesis of terminal olefins using a novel ruthenium catalyst results in excellent selectivity for the Z-olefin homodimer. The reaction was found to tolerate a large number of functional groups, solvents, and temperatures while maintaining excellent Z-selectivity, even at high reaction conversions.

Řezanka M., Eignerová B., Jindřich J., Kotora M.

Eignerová B., Slavíková B., Buděšínský M., Dračínský M., Klepetářová B., Št’astná E., Kotora M.

Three types of brassinosteroid analogues with perfluoroalkylated side chains were synthesized by using alkene cross-metathesis of a brassinosteroid derivative bearing a terminal alkene moiety with different (perfluoroalkyl)propenes. The presence of the double bonds in the cross-metathesis products allowed a facile one-step double dihydroxylation to provide intermediates that after Baeyer-Villiger oxidation afforded the target compounds. Biological activity of the prepared analogues was tested in GABA(A) receptor, cytotoxic, and brassinolide activity, which reached in some cases the same range as their nonfluorinated analogues.

Kawai K., Usui M., Ikawa S., Hoshiya N., Kishikawa Y., Shibata N.

In this study, we explore the potential of the difluoro(trifluoromethoxy)methyl group, CF2–O–CF3, an underexplored but promising structural analog of the trifluoromethoxy group (OCF3).

Buldt J.A., Kong W., Kraemer Y., Belsuzarri M.M., Patel A.H., Fettinger J.C., Tantillo D.J., Pitts C.R.

Selectivity in radical chain oligomerizations involving [1.1.1]propellane – i.e., to make [n]staffanes – has been notoriously challenging to control when n > 1 is desired. Herein, we report selective syntheses of SF5- and CF3SF4-containing [2]staffanes from SF5Cl and CF3SF4Cl, demonstrating cases whereby oligomerization is preferentially truncated after incorporation of two bicyclopentane (BCP) units. Synthetic and computational studies suggest this phenomenon can be attributed to alternating radical polarity matching. In addition, single-crystal X-ray diffraction (SC-XRD) data reveal structurally interesting features of the CF3SF4-containing [2]staffane in the solid state.

Antonova Alexandra S., Zubkov Fedor I.

Catalytic olefin metathesis using Hoveyda-Grubbs type ruthenium complexes is a powerful tool for creating complex molecules possessing a variety of practically useful properties. This method is also applied for obtaining modern polymer materials from low-demand petroleum products. Among all ruthenium complexes containing five- or six-membered chelate rings, the commercially available HG-II catalyst is the most common. In addition, other Hoveyda-Grubbs type complexes, which include a Het→Ru donor–acceptor bond in the chelate ring, often exhibit metathesis activity equal to or superior to that of HG-II. This review considers second-generation N-heterocyclic ruthenium carbene Hoveyda-Grubbs type complexes with donor–acceptor bonds such as O→Ru, S→Ru, Se→Ru, N→Ru, P→Ru and Hal→Ru in the chelate ring. Methods of preparation, analysis of stability and catalytic activity of such complexes are compared, and examples of the application of these organometallic ruthenium derivatives in the synthesis of practically relevant products are provided. The literature from 2010 to 2023 is summarized, making this review useful for a broad audience of chemists working in heterocyclic and organometallic chemistry, as well as practitioners involved in the production of catalysts and polymers.The bibliography includes 174 references.

Kraemer Y., Buldt J.A., Kong W., Stephens A.M., Ragan A.N., Park S., Haidar Z.C., Patel A.H., Shey R., Dagan R., McLoughlin C.P., Fettinger J.C., Tantillo D., Pitts C.R.

AbstractThe first assortment of achiral pentafluorosulfanylated cyclobutanes (SF5‐CBs) are now synthetically accessible through strain‐release functionalization of [1.1.0]bicyclobutanes (BCBs) using SF5Cl. Methods for both chloropentafluorosulfanylation and hydropentafluorosulfanylation of sulfone‐based BCBs are detailed herein, as well as proof‐of‐concept that the logic extends to tetrafluoro(aryl)sulfanylation, tetrafluoro(trifluoromethyl)sulfanylation, and three‐component pentafluorosulfanylation reactions. The methods presented enable isolation of both syn and anti isomers of SF5‐CBs, but we also demonstrate that this innate selectivity can be overridden in chloropentafluorosulfanylation; that is, an anti‐stereoselective variant of SF5Cl addition across sulfone‐based BCBs can be achieved by using inexpensive copper salt additives. Considering the SF5 group and CBs have been employed individually as nonclassical bioisosteres, structural aspects of these unique SF5‐CB “hybrid isosteres” were then contextualized using SC‐XRD. From a mechanistic standpoint, chloropentafluorosulfanylation ostensibly proceeds through a curious polarity mismatch addition of electrophilic SF5 radicals to the electrophilic sites of the BCBs. Upon examining carbonyl‐containing BCBs, we also observed rare instances whereby radical addition to the 1‐position of a BCB occurs. The nature of the key C(sp3)−SF5 bond formation step – among other mechanistic features of the methods we disclose – was investigated experimentally and with DFT calculations. Lastly, we demonstrate compatibility of SF5‐CBs with various downstream functionalizations.

Kraemer Y., Buldt J.A., Kong W., Stephens A.M., Ragan A.N., Park S., Haidar Z.C., Patel A.H., Shey R., Dagan R., McLoughlin C.P., Fettinger J.C., Tantillo D., Pitts C.R.

AbstractThe first assortment of achiral pentafluorosulfanylated cyclobutanes (SF5‐CBs) are now synthetically accessible through strain‐release functionalization of [1.1.0]bicyclobutanes (BCBs) using SF5Cl. Methods for both chloropentafluorosulfanylation and hydropentafluorosulfanylation of sulfone‐based BCBs are detailed herein, as well as proof‐of‐concept that the logic extends to tetrafluoro(aryl)sulfanylation, tetrafluoro(trifluoromethyl)sulfanylation, and three‐component pentafluorosulfanylation reactions. The methods presented enable isolation of both syn and anti isomers of SF5‐CBs, but we also demonstrate that this innate selectivity can be overridden in chloropentafluorosulfanylation; that is, an anti‐stereoselective variant of SF5Cl addition across sulfone‐based BCBs can be achieved by using inexpensive copper salt additives. Considering the SF5 group and CBs have been employed individually as nonclassical bioisosteres, structural aspects of these unique SF5‐CB “hybrid isosteres” were then contextualized using SC‐XRD. From a mechanistic standpoint, chloropentafluorosulfanylation ostensibly proceeds through a curious polarity mismatch addition of electrophilic SF5 radicals to the electrophilic sites of the BCBs. Upon examining carbonyl‐containing BCBs, we also observed rare instances whereby radical addition to the 1‐position of a BCB occurs. The nature of the key C(sp3)−SF5 bond formation step – among other mechanistic features of the methods we disclose – was investigated experimentally and with DFT calculations. Lastly, we demonstrate compatibility of SF5‐CBs with various downstream functionalizations.

Cheng-Sánchez I., Moya-Utrera F., Sarabia F.

Yasuo E., Aikawa K., Nozaki K., Okazoe T.

Unprecedented aryl(polyfluoroethyl)tetrafluoro-λ6-sulfanes were synthesized via the radical addition of arylchlorotetrafluoro-λ6-sulfanes to tetrafluoroethylene. The bridging tetrafluoro-λ6-sulfanyl moiety strongly enhanced the hydrophobicity.