SO2 pH Research Articles

Conversion of a AuI Fluorido Complex into an N-Fluoroamido Derivative: N-F versus Au-N Reactivity.

The AuI complex [Au{N(F)SO2 Ph}(SPhos)] (SPhos=dicyclohexyl(2',6'-dimethoxy[1,1'-biphenyl]-2-yl)phosphane) (2) bearing a fluoroamido ligand has been synthesized by reaction of the fluorido complex [Au(F)(SPhos)] (1) with NFSI (NFSI=N-fluorobenzenesulfonimide). A reaction with CO resulted in an unprecedented insertion into the N-F bond at 2. With the carbene precursor N2 CH(CO2 Et) N-F bond cleavage gave the Au-F bond insertion product [Au{CHF(CO2 C2 H5 )}(SPhos)] (7). The presence of CNtBu led to Au-N cleavage at 2 and concomitant amide formation to give the cationic complex [Au(CNtBu)(SPhos)][N(F)SO2 Ph)] (5), which reacted further to give FtBu as well as the cyanido complex [Au(CN)(SPhos)] (6). These results led to the development of a process for the amination of electrophilic organic substrates by transfer of the fluoroamido group NF(SO2 Ph)- .

Discovery of Aporphine Analogues as Potential Antiplatelet and Antioxidant Agents: Design, Synthesis, Structure-Activity Relationships, Biological Evaluations, and in silico Molecular Docking Studies.

To explore the potential of aporphine alkaloids, a novel series of functionalized aporphine analogues with alkoxy (OCH3 , OC2 H5 , OC3 H7 ) functional groups at C1/C2 of ring A and an acyl (COCH3 and COPh) or phenylsulfonyl (SO2 Ph and SO2 C6 H4 -3-CH3 ) functionality at the N6 position of ring B of the aporphine scaffold were synthesized and evaluated for their arachidonic acid (AA)-induced antiplatelet aggregation inhibitory activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical-scavenging antioxidant activity, with acetylsalicylic acid and ascorbic acid as standard references, respectively. The preliminary structure-activity relationship related to AA-induced platelet aggregation inhibitory activity results showed that the aporphine analogues 1-[1,2,9,10-tetramethoxy-6a,7-dihydro-4H-dibenzo[de,g]quinolin-6(5H)-yl]ethanone and 1-[2-(benzyloxy)-1,9,10-trimethoxy-6a,7-dihydro-4H-dibenzo[de,g]quinolin-6(5H)-yl]ethanone to be the best compounds of the series. Moreover, the DPPH free-radical-scavenging antioxidant activity results demonstrated that the aporphine analogues 1,2,9,10-tetramethoxy-6-(methylsulfonyl)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline, 2-ethoxy-1,9,10-trimethoxy-6-(methylsulfonyl)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline, 1-ethoxy-2,9,10-trimethoxy-6-(methylsulfonyl)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline, 2,9,10-trimethoxy-6-(methylsulfonyl)-1-propoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline, and 1-(benzyloxy)-2,9,10-trimethoxy-6-(methylsulfonyl)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline were the best compounds of the series. Moreover, in silico molecular docking simulation studies of the active analogues were also performed.

A Structurally Characterized Fluoroalkyne.

The facile synthesis of a stable and isolable compound with a fluoroalkynyl group, M-C≡CF, is reported. Reaction of [Ru(C≡CH)(η5 -C5 Me5 )(dppe)] with an electrophilic fluorinating agent (NFSI) results in the formation of the fluorovinylidene complex [Ru(=C=CHF)(η5 -C5 Me5 )(dppe)][N(SO2 Ph)2 ]. Subsequent deprotonation with LiN(SiMe3 )2 affords the fluoroalkynyl complex [Ru(C≡CF)(η5 -C5 Me5 )(dppe)]. In marked contrast to the rare and highly reactive examples of fluoroalkynes that have been reported previously, this compound can be readily isolated and structurally characterized. This has allowed the structure and bonding in the CCF motif to be explored. Further electrophilic fluorination of this species yields the difluorovinylidene complex [Ru(C=CF2 )(η5 -C5 Me5 )(dppe)][N(SO2 Ph)2 ].

Metal-Ligand Cooperativity in a Methandiide-Derived Iridium Carbene Complex.

The synthesis, electronic structure, and reactivity of the first Group 9 carbene complex, [Cp*IrL] [L=C(Ph2 PS)(SO2 Ph)] (2), based on a dilithio methandiide are reported. Spectroscopic as well as computational studies have shown that, despite using a late transition-metal precursor, sufficient charge transfer occurred from the methandiide to the metal, resulting in a stable, nucleophilic carbene species with pronounced metal-carbon double-bond character. The potential of this iridium complex in the activation of a series of E-H bonds by means of metal-ligand cooperation has been tested. These studies have revealed distinct differences in the reactivity of 2 compared to a previously reported ruthenium analogue. Whereas attempts to activate the O-H bond in different phenol derivatives resulted in ligand cleavage, H-H and Si-H activation as well as dehydrogenation of isopropanol have been accomplished. These reactions are driven by the transformation of the carbene to an alkyl ligand. Contrary to a previously reported ruthenium carbene system, the dihydrogen activation has been found to proceed by a stepwise mechanism, with the activation first taking place solely at the metal. The activated products further reacted to afford a cyclometalated complex through liberation of the activated substrates. In the case of triphenylsilane, cyclometalation could thus be induced by a substoichiometric (i.e., catalytic) amount of silane.

Chiral Lithiated Allylic α-Sulfonyl Carbanions: Experimental and Computational Study of Their Structure, Configurational Stability, and Enantioselective Synthesis.

X-ray crystal structure analysis of the lithiated allylic α-sulfonyl carbanions [CH2 CHC(Me)SO2 Ph]Li⋅diglyme, [cC6 H8 SO2 tBu]Li⋅PMDETA and [cC7 H10 SO2 tBu]Li⋅PMDETA showed dimeric and monomeric CIPs, having nearly planar anionic C atoms, only OLi bonds, almost planar allylic units with strong CC bond length alternation and the s-trans conformation around C1C2. They adopt a C1S conformation, which is similar to the one generally found for alkyl and aryl substituted α-sulfonyl carbanions. Cryoscopy of [EtCHCHC(Et)SO2 tBu]Li in THF at 164 K revealed an equilibrium between monomers and dimers in a ratio of 83:17, which is similar to the one found by low temperature NMR spectroscopy. According to NMR spectroscopy the lone-pair orbital at C1 strongly interacts with the CC double bond. Low temperature (6) Li,(1) H NOE experiments of [EtCHCHC(Et)SO2 tBu]Li in THF point to an equilibrium between monomeric CIPs having only OLi bonds and CIPs having both OLi and C1Li bonds. Ab initio calculation of [MeCHCHC(Me)SO2 Me]Li⋅(Me2 O)2 gave three isomeric CIPs having the s-trans conformation and three isomeric CIPs having the s-cis conformation around the C1C2 bond. All s-trans isomers are more stable than the s-cis isomers. At all levels of theory the s-trans isomer having OLi and C1Li bonds is the most stable one followed by the isomer which has two OLi bonds. The allylic unit of the C,O,Li isomer shows strong bond length alternation and the C1 atom is in contrast to the O,Li isomer significantly pyramidalized. According to NBO analysis of the s-trans and s-cis isomers, the interaction of the lone pair at C1 with the π* orbital of the CC double bond is energetically much more favorable than that with the "empty" orbitals at the Li atom. The C1S and C1C2 conformations are determined by the stereoelectronic effects nC -σSR * interaction and allylic conjugation. (1) H DNMR spectroscopy of racemic [EtCHCHC(Et)SO2 tBu]Li, [iPrCHCHC(iPr)SO2 tBu]Li and [EtCHC(Me)C(Et)SO2 tBu]Li in [D8 ]THF gave estimated barriers of enantiomerization of ΔG(≠) =13.2 kcal mol(-1) (270 K), 14.2 kcal mol(-1) (291 K) and 14.2 kcal mol(-1) (295 K), respectively. Deprotonation of sulfone (R)-EtCHCHCH(Et)SO2 tBu (94 % ee) with nBuLi in THF at -105 °C occurred with a calculated enantioselectivity of 93 % ee and gave carbanion (M)-[EtCHCHC(Et)SO2 tBu]Li, the deuteration and alkylation of which with CF3 CO2 D and MeOCH2 I, respectively, proceeded with high enantioselectivities. Time-dependent deuteration of the enantioenriched carbanion (M)-[EtCHCHC(Et)SO2 tBu]Li in THF gave a racemization barrier of ΔG(≠) =12.5 kcal mol(-1) (168 K), which translates to a calculated half-time of racemization of t1/2 =12 min at -105 °C.

Preparation of new polysulfones with –O–(CH2)3–SO3H side chains

New polymer electrolytes consisting of diphenyl sulfone units with –O–(CH2)3SO3M (M=H or Na) side chains have been prepared. Dehalogenative polycondensation using a zero-valent nickel complex, [Ni(0)Lm], gave a homopolymer, Polymer-1(Na), from Cl–Ph(R)–SO2–Ph(R)–Cl (monomer-1; Ph(R)=1,3-phenylene unit having the –O–(CH2)3SO3Na side group at the 4-position). Protonolysis of Polymer-1(Na) gave Polymer-1(H) with a weight average molecular weight of 25,000. Polymer-2(H) was synthesized by Suzuki-Miyaura cross coupling of Br–Ph(R)–SO2–Ph(R)–Br (monomer-2) and C6H4(B(OH)2)2-p using [Pd(PPh3)4] and ensuing protonolysis. Crosslinking of Polymer-2(H) with 1,4-benzenedimethanol gave a water-protected film. The cross-linked film of Polymer-2(H) showed proton conductivity of 0.26Scm−1 at 80°C and 90% humidity.

Facile synthesis of α-monofluoromethyl alcohols: Nucleophilic monofluoromethylation of aldehydes using TMSCF(SO 2Ph) 2

α-Fluoromethyl phenyl sulfone derivatives have been extensively employed in various reactions as versatile fluoromethylating reagents. While nucleophilic monofluoromethylations of aldehydes have been achieved using fluoromethyl phenyl sulfone or fluorobis(sulfonyl)methanes, a facile protocol under mild reaction conditions remains an ardently sought goal. We now report a feasible synthetic approach toward β-monofluorinated alcohols using α-trimethylsilyl-α-fluorobis(phenylsulfonyl)methane [TMSCF(SO 2Ph) 2, TFBSM] as a novel monofluoromethylating reagent. Initiated by a catalytic amount of fluoride, the reagent can be readily added to a variety of aldehydes providing the desired products in high yields. Computational and kinetic studies have revealed the exceptional lability of the Si–C bond in TFBSM compared with other fluoromethylsilane counterparts.

Synthesis and evaluation of vinyl sulfones as caspase-3 inhibitors. A structure–activity study

The first structure–activity relationship study of vinyl sulfones as caspase-3 inhibitors is reported. A series of 12 vinyl sulfones was synthesized and evaluated for two downstream caspases (caspases-3 and -7). Dipeptidyl derivatives were significantly superior to their counterparts containing only Asp at P 1, as caspase-3 inhibitors. Fmoc-Val-Asp- trans-CH CH–SO 2Me was the most potent inhibitor of caspase-3 in the series, with a IC 50 of 29 μM and a second-order rate constant of inactivation, k inact/ K i, of 1.5 M −1 s −1. Computational studies suggest that the second amino acid occupies position S 3 of the enzyme. In addition, Fmoc-Val-Asp- trans-CH CH–SO 2Ph was inactive for caspase-7 for the tested concentrations.

Lithiated γ- O-functionalized propyl phenyl sulfides and sulfones of the type Li[CH(SO xPh)CH 2CH 2OR] ( x = 0, 2). [Li{CH(SPh)CH 2CH 2O t-Bu}(tmeda)] – A structurally characterized organolithium inner complex

Lithiation of O-functionalized alkyl phenyl sulfides PhSCH 2CH 2CH 2OR (R = Me, 1a; i-Pr, 1b; t-Bu, 1c; CPh 3, 1d) with n-BuLi/tmeda in n-pentane resulted in the formation of α- and ortho-lithiated compounds [Li{CH(SPh)CH 2CH 2OR}(tmeda)] (α- 2a– d) and [Li{ o-C 6H 4SCH 2CH 2CH 2OR)(tmeda)] ( o- 2a– d), respectively, which has been proved by subsequent reaction with n-Bu 3SnCl yielding the requisite stannylated γ-OR-functionalized propyl phenyl sulfides n-Bu 3SnCH(SPh)CH 2CH 2OR (α- 3a– d) and n-Bu 3Sn( o-C 6H 4SCH 2CH 2CH 2OR) ( o- 3a– d). The α/ ortho ratios were found to be dependent on the sterical demand of the substituent R. Stannylated alkyl phenyl sulfides α- 3a– c were found to react with n-BuLi/tmeda and n-BuLi yielding the pure α-lithiated compounds α- 2a– c and [Li{CH(SPh)CH 2CH 2OR}] (α- 4a– b), respectively, as white to yellowish powders. Single-crystal X-ray diffraction analysis of [Li{CH(SPh)CH 2CH 2O t-Bu}(tmeda)] (α- 2c) exhibited a distorted tetrahedral coordination of lithium having a chelating tmeda ligand and a C, O coordinated organyl ligand. Thus, α- 2c is a typical organolithium inner complex. Lithiation of O-functionalized alkyl phenyl sulfones PhSO 2CH 2CH 2CH 2OR (R = Me, 5a; i-Pr, 5b; CPh 3, 5c) with n-BuLi resulted in the exclusive formation of the α-lithiated products Li[CH(SO 2Ph)CH 2CH 2OR] ( 6a– c) that were found to react with n-Bu 3SnCl yielding the requisite α-stannylated compounds n-Bu 3SnCH(SO 2Ph)CH 2CH 2OR ( 7a– c). The identities of all lithium and tin compounds have been unambiguously proved by NMR spectroscopy ( 1H, 13C, 119Sn).

Zirconium-catalyzed methylalumination of heterosubstituted arylethynes: Factors affecting the regio-, stereo-, and chemoselectivities

The Zr-catalyzed methylalumination of heterosubstituted arylethynes containing O, S, Cl, and Si can proceed in high yields (>70%) and in a highly regio- and stereoselective manner (⩾98–99%), although SO 2Ph, Br, and Cl in a benzylic position present serious chemoselectivity-related problems. The low regioselectivity of 60% initially observed with o-ethynylphenol ( 1a) has been elevated to ⩾98% through the use of either a catalytic amount of Zr(ebi)Cl 2 or Zr(2-Me-Ind) 2Cl 2 or, more conveniently, the stoichiometric amount of ZrCp 2Cl 2, ZrCp 2MeCl, or ZrCp 2Me 2 in conjunction with the use of a deficient amount (0.9 molar equiv.) of I 2 for subsequent iodinolysis.

Theoretical insights of copper(I)–nitrene complexes

Density functional theory has been used to study the geometries and character of the copper–nitrene complexes L n Cu N R ( 1, R = Me; 2, R = CO 2Me; 3, R = SO 2Me; 4, R = SO 2ph). Calculation results confirm that the copper–nitrene nitrogen bonds of the copper–nitrene complexes A2, B2, C2, and D2 (R=CO 2Me) show strong double-bonded character, and thus those of the copper–nitrene complexes A1, A3, A4, B1, B3, B4, C1, C3, C4, D1, D3, D4, E1, E2, E3, E4, F1, F2, F3, and F4 show single-bonded character. The copper–nitrene nitrogen bonds and the copper and nitrogen atoms of the bonds are the reactive center for the copper–nitrene complexes. The geometry, electronic structure, frontier orbitals (HOMO and LUMO), and molecular electrostatic potential (MEP) are discussed in detail.

Syntheses and structures of lithiated sulfones Li[CR(R′)SO 2Ph] – C versus O bound lithium. [{Li{CH(Me)SO 2Ph}(thf)} ∞] – The structure of a C-bound derivative

Sulfones RCH(R′)SO 2Ph were reacted with n-BuLi in thf/ n-hexane (R/R′ = H/Me, Me/Et, H/CH 2Ph) and toluene/ n-hexane (R/R′ = Me/Ph) yielding under deprotonation Li[CR(R′)SO 2Ph] which reacted with Me 3SiCl and n-Bu 3SnCl forming the requisite trimethylsilyl and tri( n-butyl)tin substituted derivatives R 3 ″ E - C ( R ) R ′ SO 2 Ph ( R 3 ″ E = Me 3 Si , n - Bu 3 Sn ) . Performing the reactions of RCH(R′)SO 2Ph with n-BuLi in n-hexane (instead of thf/ n-hexane) and toluene/ n-hexane, respectively, resulted in the precipitation of the organo lithium compounds Li[CR(R′)SO 2Ph] ( 1– 4) which were isolated as strongly moisture-sensitive yellow powders in essentially quantitative yields. Their identities were confirmed by 1H and 13C NMR spectroscopic measurements in thf- d 8. Solutions of each 1, 3, and 4 in thf/ n-hexane and thf/ n-pentane afforded crystals of each [{Li{CH(Me)SO 2Ph}(thf)} ∞] ( 1a), [{Li{CH(CH 2Ph)SO 2Ph}(thf)} ∞] ( 3a), and [{Li{CMe(Ph)SO 2Ph}(thf) 2} 2] ( 4a), respectively, whose structures were determined by single-crystal X-ray crystallography. The compounds 1a and 3a crystallize in 1D polymeric ladder-like structures. The strands of 1a are built-up by eight-membered Li 2C 2S 2O 2 rings having direct Li–C bonding interactions (Li–C 2.215(5) Å). The donor set of Li is completed by three oxygen atoms, one from the thf ligand and two from SO 2 groups of neighboring Li{CH(Me)SO 2Ph}(thf) entities. The strands of 3a are built-up of alternating Li 2S 2O 4 eight- and Li 2O 2 four-membered rings. Each lithium atom is coordinated to three oxygen atoms, two from O 2S(Ph)CHCH 2Ph groups and one from thf oxygen atom. There is no Li–C bonding. Compound 4a crystallizes in dimers consisting of eight-membered Li 2S 2O 4 rings in which the two lithium atoms are bridged by two O 2S(Ph)CHMePh groups. The coordination sphere of lithium is completed by two oxygen atoms of the thf ligands.

Ring expansion of 5- to 6-member zirconacycles by carbenoid insertion

A wide range of carbenoids (1-lithio-1-halo species), including those with α-SiR 3, OEt, SPh, SO 2Ph, P(O)(OEt) 2, and CN substituents, insert into 5-member zirconacycles (saturated and unsaturated, mono- and bi-cyclic) to afford functionalized 6-member zirconacycles. 1-Lithio-1-haloalkenes insert to afford 6-member zirconacycles with an alkylidene substituent next to the metal. Unexpected double insertion of some carbenoids, and evidence for endocylic β-hydride transfer processes provide additional mechanistic interest.

Preparation of α-functionalized alkenylmagnesium reagents via a halide–magnesium exchange

A general preparation of alkenylmagnesium derivatives bearing an electron-withdrawing function in the α-position (Y=CN, CO 2R, CONR 2, SO 2Ph) has been made possible by using a low temperature (−40 to −30°C) bromine–magnesium exchange with i-PrMgBr in THF. This reaction has also been used to prepare 5-magnesiated-1,3-dioxin-4-one derivatives bearing an alkoxy substituent in β-position to the carbon–magnesium bond.

Generation and in situ Diels–Alder reactions of activated nitroethylene derivatives

Dienes readily undergo Diels–Alder reaction with CH 2C(NO 2)SO 2Ph ( 2a ), CH 2C(NO 2)CO 2Et ( 2b ), and CH 2C(NO 2)COPh ( 2c ), all observed in situ by 1H NMR. The cycloadducts of 2a undergo S RN1 reactions.

Observations on the alkylation of β-acetalic carbanions: monoalkylation versus dialkylation and elimination

The reaction with methyl iodide and a base ( t-BuOK) of 1,3-dioxolanes and 1,3-dithiolanes substituted at the β-position with an electron-withdrawing substituent (EWG=CO 2Me, SO 2Ph, SO 2Ph- p-NO 2, SO 2Ph- o-NO 2) leads to mono- or dialkylated or ring-opened products in good yield.

Metallacyclic platinum(II) bis(sulfonamides)

A series of metallacyclic platinum(II) bis(sulfonamido) complexes have been synthesised by reaction of cis-[PtCl 2L 2] [L=PPh 3 or L 2=1,5- cyclo-octadiene (cod)] with the sulfonamides [RSO 2NHCH 2CH 2NHSO 2R, RSO 2NHCH 2CHMeNHSO 2R or RSO 2NHC 6H 4NHSO 2R; R=Ph or p-C 6H 4Me] and Ag 2O. The products have been characterised by NMR spectroscopy, electrospray mass spectrometry, elemental analysis, and for the complexes [ Pt{N(SO 2Ph)CH 2CH 2N (SO 2Ph)}(PPh 3) 2] and [ Pt{N(SO 2Ph)C 6H 4N (SO 2Ph)}(cod)], by single-crystal X-ray structure determinations. In both of these complexes, one of the amido nitrogen atoms has the expected approximately planar geometry, but the other nitrogen atom is surprisingly distorted towards a tetrahedral geometry. The more pyramidal nitrogen has a higher trans-influence in the solid state, reflected by a shorter PtN bond, and longer cyclo-octadiene PtC bond length trans to this nitrogen.

Radical cyclisation onto nitriles

Iminyl radicals, generated by 5- exo cyclisation of alkyl, vinyl and aryl C-centred radicals onto nitriles, undergo β-scission (nitrile translocation), reduction or tandem cyclisation onto alkenes depending on the nature of the α-substituent. 5- exo Cyclisations of aryl radicals onto nitriles undergo nitrile translocation when the α-substituent is CN, CO 2R, SO 2Ph or CONMe 2. The rate of translocation is faster than 5- or 6- exo cyclisation onto alkenes or 1,5-hydrogen abstraction of allylic hydrogens. When the α-substituents are alkyl, the intermediate iminyl radicals do not undergo nitrile translocation.

Highly stereoselective additions of sulfur stabilized carbanions to [(S) R]-2-( p-tolylsulfinyl)cyclohexanones

We describe the addition reactions of α-thiocarbanions derived from sulfoxides, thioethers, and sulfones to 2-( p-tolylsulfinyl)cyclohexanones. The high stereoselectivity observed in the formation of the chiral hydroxylic carbon is controlled by the configuration of the sulfinyl group at the substrate, but it is modulated by the nature of the sulfur function at the reagent (SOTol>SO 2Ph>SPh). The highly stereoselective formation of the second stereogenic center generated in these reactions from prochiral anions is only achieved with sulfinylcarbanions, the configuration of which controls that of such a center.

Carbenoid insertion into alkenylzirconocenes—a convergent synthesis of functionalised allylmetallics

Insertion of lithium alkylcarbenoids RC(A)LiX, A=CN, P(O)(OEt) 2, SO 2Ph, OMe into alkenylzirconocene chlorides derived by hydrozirconation of terminal alkynes affords functionalised allylzirconium reagents which may be further elaborated.