A new class of dianionic sulfur-ylides: alkylenediazasulfites

The compounds [[(thf)Li2-[H2CS(NtBu)2]]2] (1) and [((thf)Li2[(Et)-(Me)CS(NtBu)2])2] (2) can be synthesized in a two-step reaction. Firstly addition of an alkyllithium to sulfur diimide gives the diazaalkylsulfinate [RS(NtBu)2] (R =Me, sBu). In a second step the alpha-carbon atom in R is metalated with one equivalent of methyllithium to give the S-ylides. This new class of compounds can be rationalized as sulfite analogues, in which two oxygen atoms are each isoelectronically replaced by a NtBu group and the remaining oxygen atom is replaced by a CR2 group. Similar to Corey's S-ylides (R2(O)S+-CR2) and Wittig's phosphonium ylides (R3P+ - -CR2), these molecules contain a positively charged sulfur atom next to a carbanionic center. Therefore nucleophilic addition reactions of the carbon atom are feasible. The reaction of a sulfur diimide with the anionic carbon center in [H2CS-(NtBu)2]2- gives the intermediate alkylbis(diazasulfinate) [(tBuN)2SCH2S(NtBu)2]2-. The acidity of the hydrogen atoms at the bridging CH2 group is high enough to give, upon deprotonation, the [(tBuN)2SCHS(NtBu)2]3- trianion in [[(thf)Li3[(tBuN)2SCHS(NtBu)2]]2] (3). In [(Et)(Me)CS(NtBu)2]2 the nucleophilic carbon atom is sterically hindered and transimidation instead of deprotonation is observed. In a complex redox process [(thf)6Li6S((NtBu)3S]2] is recovered. The two new classes of compounds broaden the rich coordination chemistry of the triazasulfites by the introduction of a hard carbon center.     

Mechanism of S-oxygenation by a cysteine dioxygenase model complex

In this work, we present the first computational study on a biomimetic cysteine dioxygenase model complex, [Fe(II)(LN(3)S)](+), in which LN(3)S is a tetradentate ligand with a bis(imino)pyridyl scaffold and a pendant arylthiolate group. The reaction mechanism of sulfur dioxygenation with O(2) was examined by density functional theory (DFT) methods and compared with results obtained for cysteine dioxygenase. The reaction proceeds via multistate reactivity patterns on competing singlet, triplet, and quintet spin state surfaces. The reaction mechanism is analogous to that found for cysteine dioxygenase enzymes (Kumar, D.; Thiel, W.; de Visser, S. P. J. Am. Chem. Soc. 2011, 133, 3869-3882); hence, the computations indicate that this complex can closely mimic the enzymatic process. The catalytic mechanism starts from an iron(III)-superoxo complex and the attack of the terminal oxygen atom of the superoxo group on the sulfur atom of the ligand. Subsequently, the dioxygen bond breaks to form an iron(IV)-oxo complex with a bound sulfenato group. After reorganization, the second oxygen atom is transferred to the substrate to give a sulfinic acid product. An alternative mechanism involving the direct attack of dioxygen on the sulfur, without involving any iron-oxygen intermediates, was also examined. Importantly, a significant energetic preference for dioxygen coordinating to the iron center prior to attack at sulfur was discovered and serves to elucidate the function of the metal ion in the reaction process. The computational results are in good agreement with experimental observations, and the differences and similarities of the biomimetic complex and the enzymatic cysteine dioxygenase center are highlighted.     

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>SO₂Ph>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.     

Iron Carbonyl Complexation of Dithioesters. Formation of a Chiral Carbon Center σ-Bonded to an Iron Atom

Dithioesters react with diiron nonacarbonyl to afford binuclear complexes resulting from coordination of the carbon—sulfur double bond to the two iron atoms and donation of two electrons from the S-alkyl group to one iron center. This novel mode of complexation creates a carbon—iron single bond and a chiral center at the carbon atom bonded to the metal, as shown by the spectroscopic studies and by an X-ray structure determination,     

The intramolecular sila-Pummerer cyclization: A new route to sulfur heterocycles

The generality of the intramolecular cyclization of suitable nucleophilic sites to a  S⁺CH₂ center created by a sila-Pummerer rearrangement has been investigated. Successful nucleophilic sites included the OH group (in alcohols, carboxylic acids, and hydroxylamines) and the NH group (in amines and carbamates): attempts to produce carbon-based nucleophilic sites were not effective. Successful cyclizations were achieved to produce sulfur heterocycles with 5-, 6-, and 7-membered rings.     

[Pd{2-CH2-5-MeC6H3C(H)NNC(S)NHEt}]3: An unprecedented trinuclear cyclometallated palladium(II) cluster through induced flexibility in the metallated ring

The reaction of 1-(2,5-dimethylbenzylidene)-3-ethylthiosemicarbazone and palladium acetate in acetic acid yields a trinuclear cyclometallated palladium(II) compound. Each thiosemicarbazone ligand is tridentate with the metal bonded to the carbon atom from the 2-methyl group, to the azomethine nitrogen and to the sulfur atom, which bridges to an adjacent palladium center. The crystal structure confirms the presence of a non-planar hexagonal metallated ring plus a central six-membered palladium-sulfur core within the trimer, which also displays a rather deep intramolecular cavity.     

The heliobacteria, a new group of photosynthetic bacteria

A review is given of the photosynthetic properties of the heliobacteria, a new group of photosynthetic bacteria, discovered only 14 years ago. These bacteria contain a “new” pigment, bacteriochlorophyll g, and they have a relatively simple pigment system, consisting of a core-reaction center complex only. Like the green sulfur bacteria, they have a Photosystem I-type reaction center, with a chlorophyll a derivative as primary electron acceptor. Because of the absence of an extensive peripheral antenna system, the reaction center processes in these bacteria are much easier to study than those in the green sulfur bacteria.     

"Sulfolefin": highly modular mixed S/olefin ligands for enantioselective Rh-catalyzed 1,4-addition

Reported is a single high yielding step approximation to mixed olefin/sulfinamide ligands enclosing a chiral sulfur atom as the sole chiral center. The synthetic design is validated by a rapid optimization of the substituent at the sulfinyl sulfur, and by the synthesis of an efficient, highly enantioselective catalyst for the Rh-catalyzed 1,4-addition of boronic acids to both, cyclic and acyclic olefins.     

THE CHEMISTRY OF OPTICALLY ACTIVE SULFUR COMPOUNDS PART III

Abstract

The chemistry of optically active sulfur compounds has proven to be one of great interest and challenge as demonstrated by the prolific publications in this area. An ever larger number of different types of compounds with sulfur as center of chirality are being synthesized and it is expected that in future publications additional members of this group will be described. Thus far the following chiral sulfur compounds have been prepared:     

Specific hydration effects on oxo-thio triazepine derivatives

The specific hydration of 2,7-dimethyl-1,2,4-triazepine oxo-thio derivatives by one water molecule has been investigated at the B3LYP/6-311++G(3df,2p)//B3LYP/6-311+G(d,p) level of theory. The existence of different hydrogen bond (HB) donor and acceptor centers in these molecules led to different kinds of hydrogen bonds (CH-O, OH-S, NH-O, OH-N, and OH-O) and different kinds of complexes. Among them, the most stable structures correspond to complexes where the heteroatom X or Y at positions 3 and 5 behaves as HB acceptor and the hydrogen atom associated with the nitrogen atom at position 4 as HB donor. In accordance with previous studies, it has been shown that the thiocarbonyl group forms stronger HBs than the carbonyl group because the sulfur atom is a better HB acceptor than the oxygen one. With the help of the AIM (atoms in molecules) theory and ELF (electron localization function) analysis, it has been shown that, in the case of 3O5O, 3S5O, and 3S5S, the most basic site is the heteroatom at position 3, while in 3O5S species the most basic center is the sulfur atom.     

焦炭中硫的空间分布规律研究

采用炼焦混合煤模拟工业焦化过程，研究了焦炭中硫的空间分布规律。结果表明，焦炭柱同一高度的有机硫、无机硫的质量分数从中心到边缘逐渐升高；相同取样位置处裂纹表面的有机硫、无机硫比对应内部位置硫的质量分数高；对于炭化室直径为230mm的模拟实验，有机硫增加约0.035%，无机硫增加约0.08%。XPS分析显示，有机硫与无机硫的质量分数的差异是由噻吩硫及金属硫化物的质量分数不同造成的。二维相似模拟实验进一步证实焦炭柱中硫的质量分数从中心沿径向到边缘逐渐升高。     

硫醚中碳硫键室温选择性断裂反应的研究

本文研究了在四氟硼酸银存在下, 硫醚与碘甲烷室温下发生碳硫键选择性断裂反应。研究结果表明: 只有当二苄基硫醚的苯环对位连有强的供电子基团甲氧基时, 方可发生碳硫键的断裂。提出了一个离子型反应机理且碳硫键的断裂分三步完成。首先, 硫醚与甲基化试剂反应生成甲基锍盐; 继而, 此锍离子离解成由苄基碳正离子和硫醚组成的离子-偶极集合物; 最后, 甲基化试剂再进攻集合物中的硫醚, 从而导致碳硫键的断裂。     

Organocatalytic asymmetric sulfa-Michael addition of thiols to 4,4,4-trifluorocrotonates

The first asymmetric sulfa-Michael addition of thiols to 4,4,4-trifluorocrotonates for the construction of a stereogenic center bearing a unique trifluoromethyl group and a sulfur atom has been achieved in high yields and excellent enantioselectivities with a 1 mol % bifunctional organocatalyst. Subsequent transformation led to the expedient preparation of enantioenriched thiochroman-4-one and the key intermediate of the potent inhibitor of MMP-3, (R)-γ-trifluoromethyl γ-sulfone hydroxamate.     

Evidence for a nonradical pathway in the photoracemization of aryl sulfoxides

Photolysis of (R(S),S(C))-1-deuterio-2,2-dimethylpropyl p-tolyl sulfoxide provides mainly (S(S),S(C))-1-deuterio-2,2-dimethylpropyl p-tolyl sulfoxide at low conversion, though the other two stereoisomers are formed to smaller extents. Thus, the predominant process leading to sulfur inversion yields only sulfur inversion, without inversion of the adjacent CHD stereogenic center. This is taken as evidence for a mechanism for photochemical epimerization of sulfoxides that does not involve homolytic alpha-cleavage chemistry.     

A mechanism from quantum chemical studies for methane formation in methanogenesis

The mechanism for methane formation in methyl-coenzyme M reductase (MCR) has been investigated using the B3LYP hybrid density functional method and chemical models consisting of 107 atoms. The experimental X-ray crystal structure of the enzyme in the inactive MCR(ox1)(-)(silent) state was used to set up the initial model structure. The calculations suggest a mechanism not previously proposed, in which the most remarkable feature is the formation of an essentially free methyl radical at the transition state. The reaction cycle suggested starts from a Michaelis complex with CoB and methyl-CoM coenzymes bound and with a squareplanar coordination of the Ni(I) center in the tetrapyrrole F(430) prosthetic group. In the rate-limiting step the methyl radical is released from methyl-CoM, induced by the attack of Ni(I) on the methyl-CoM thioether sulfur. In this step, the metal center is oxidized from Ni(I) to Ni(II). The resulting methyl radical is rapidly quenched by hydrogen-atom transfer from the CoB thiol group, yielding the methane molecule and the CoB radical. The estimated activation energy is around 20 kcal/mol, which includes a significant contribution from entropy due to the formation of the free methyl. The mechanism implies an inversion of configuration at the reactive carbon. The size of the inversion barrier is used to explain the fact that CF(3)-S-CoM is an inactive substrate. Heterodisulfide CoB-S-S-CoM formation is proposed in the final step in which nickel is reduced back to Ni(I). The suggested mechanism agrees well with experimental observations.     

Central (S) to Central (M=Ir,Rh) to Planar (Metallocene,M=Fe,Ru) Chirality Transfer Using Sulfoxide-Substituted Mesoionic Carbene Ligands: Synthesis of Bimetallic Planar Chiral Metallocenes

Enantiopure bimetallic systems containing three different elements of chirality, namely a main-group-based chiral center (sulfur), a transition-metal chiral center (rhodium or iridium), and a planar chiral element (ferrocene or ruthenocene), have been prepared by a sequence of diastereoselective reactions. The chirality of the chiral sulfur center attached to C-5 of a 1,2,3-triazolylidene mesoionic carbene (MIC) ligand coordinated to a metal (Ir, Rh) was transferred through the formation of bimetallic complexes having a chiral-at-metal center and a planar chiral metallocene by C−H activation of the sandwich moiety (M=Fe, Ru). The sense of the planar chirality formed in this sequence of reactions depended on the nature of the ligands at the metal center of the starting complex. The configurations of these species were assigned on the basis of a combination of X-ray diffraction and CD measurements. An electrochemical study of these bimetallic complexes in coordinating solvents showed an equilibrium between the cationic complexes and the neutral species. The effect of the half-sandwich moiety on the oxidation potentials of the system is remarkable, producing notable cathodic displacements. DFT calculations support these findings.     

Trigonal prismatic vs octahedral coordination geometry: syntheses and structural characterization of hexakis(arylthiolato) zirconate complexes

Treating [Li(tmeda)]2[Zr(CH3)6] with aryl thiols, HSC6H4-4-R, in a 1:6 stoichiometry in diethyl ether affords excellent yields of [Li(tmeda)]2[Zr(SC6H4-4-R)6], where R = CH3 (1(2-)) or OCH3 (2(2-)) and tmeda denotes N,N,N',N'-tetramethylethylenediamine. These complexes are air-sensitive canary-yellow solids, soluble in hexane, diethyl ether, THF, and acetonitrile, that form yellow single crystals of [Li(tmeda)](2)1 (diethyl ether solution) or [Li(THF)3](2)2 (THF solution) from saturated solutions at -20 degrees C. Both complexes were characterized by X-ray crystallography and consist of a zirconium atom coordinated solely by the sulfur atoms of six aryl thiolate ligands in a nonoctahedral geometry. In each structure the lithium cation coordinates to the three sulfur atoms on the triangular faces of the S6 pseudotrigonal prism. These lithium-sulfur interactions appear to play a role in determining the coordination geometry about the metal center by orienting the sulfur lone pairs of electrons slightly out of the plane defined by the S3 triangular face and tilted away from the zirconium atoms. A likely consequence is the positioning of the sulfur lone pairs of electrons away from orthogonality with the zirconium-sulfur vector, and hence, they are poorly arranged to pi-interact with zirconium. Complex 1(2-) with a twist angle of ca. 9.18 degrees (trigonal prism, 0 degree; octahedron, 60 degrees) agrees with the interpretations of computational studies on d degree complexes, which suggest that a nearly trigonal prismatic geometry is favored when the interaction between metal and ligand is primarily through sigma-bonds. The intrinsically weak pi-donor thiolate ligand is probably converted to a primarily sigma-bonding system by the lithium-sulfur interaction. On the other hand complex 2(2-) with a twist angle of ca. 30.38 degrees is trigonally twisted to the midpoint of the trigonal prismatic-to-octahedral reaction coordinate. In complex 2(2-) the 4-OCH3 group is an electron donor by resonance effects that possibly may lead to the movement away from the expected trigonal prismatic geometry due to either pi-interactions or electrostatics repulsion.     

S-oxygenation of thiocarbamides II: Oxidation of trimethylthiourea by chlorite and chlorine dioxide

The kinetics of the oxidation of a substituted thiourea, trimethylthiourea (TMTU), by chlorite have been studied in slightly acidic media. The reaction is much faster than the comparable oxidation of the unsubstituted thiourea by chlorite. The stoichiometry of the reaction was experimentally deduced to be 2ClO2- + Me2N(NHMe)C=S + H2O --> 2Cl- + Me2N(NHMe)C=O + SO4(2-) + 2H+. In excess chlorite conditions, chlorine dioxide is formed after a short induction period. The oxidation of TMTU occurs in two phases. It starts initially with S-oxygenation of the sulfur center to yield the sulfinic acid, which then reacts in the second phase predominantly through an initial hydrolysis to produce trimethylurea and the sulfoxylate anion. The sulfoxylate anion is a highly reducing species which is rapidly oxidized to sulfate. The sulfinic and sulfonic acids of TMTU exists in the form of zwitterionic species that are stable in acidic environments and rapidly decompose in basic environments. The rate of oxidation of the sulfonic acid is determined by its rate of hydrolysis, which is inhibited by acid. The direct reaction of chlorine dioxide and TMTU is autocatalytic and also inhibited by acid. It commences with the initial formation of an adduct of the radical chlorine dioxide species with the electron-rich sulfur center of the thiocarbamide followed by reaction of the adduct with another chlorine dioxide molecule and subsequent hydrolysis to yield chlorite and a sulfenic acid. The bimolecular rate constant for the reaction of chlorine dioxide and TMTU was experimentally determined as 16 +/- 3.0 M(-1) s(-1) at pH 1.00.     

Glutathione peroxidase (GPx)-like antioxidant activity of the organoselenium drug ebselen: unexpected complications with thiol exchange reactions

The factors that are responsible for the relatively low glutathione peroxidase (GPx)-like antioxidant activity of organoselenium compounds such as ebselen (1, 2-phenyl-1,2-benzisoselenazol-3(2H)-one) in the reduction of hydroperoxides with aromatic thiols such as benzenethiol and 4-methylbenzenethiol as cosubstrates are described. Experimental and theoretical investigations reveal that the relatively poor GPx-like catalytic activity of organoselenium compounds is due to the undesired thiol exchange reactions that take place at the selenium center in the selenenyl sulfide intermediate. This study suggests that any substituent that is capable of enhancing the nucleophilic attack of thiol at sulfur in the selenenyl sulfide state would enhance the antioxidant potency of organoselenium compounds such as ebselen. It is proved that the use of thiol having an intramolecularly coordinating group would enhance the biological activity of ebselen and other organoselenium compounds. The presence of strong S...N or S...O interactions in the selenenyl sulfide state can modulate the attack of an incoming nucleophile (thiol) at the sulfur atom of the -Se-S- bridge and enhance the GPx activity by reducing the barrier for the formation of the active species selenol.     

An asymmetric synthesis of carboxylic acid derivatives,including lactic acid and α-amino acid derivatives,from optically active 1-chlorovinyl p-tolyl sulfoxides and ester lithium enolates with creation of chirality at the α-position

Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from symmetrical ketones or methyl formate and (R)-(−)-chloromethyl p-tolyl sulfoxide in three steps, with lithium enolate of carboxylic acid tert-butyl esters gave optically active adducts having a substituent (alkyl, alkoxy, or dibenzylamino group) at the α-position with high 1,4-chiral induction from the sulfur chiral center. The adducts were converted to optically active esters, lactic acid, and α-amino acid derivatives having a chiral center at the α-position. When this addition reaction was carried out with an ester enolate generated from excess carboxylic acid tert-butyl ester with LDA in the presence of HMPA, the diastereomer of the adduct was obtained. By using the two reaction conditions for the generation of the ester enolate, a new method for asymmetric synthesis of both enantiomers of carboxylic acid derivatives having a substituent at the α-position from the one chiral source, (R)-(−)-chloromethyl p-tolyl sulfoxide, was achieved.