Trans Adducts Research Articles

Isolation and Electronic Structures of Lanthanide(II) Bis(trimethylsilyl)phosphide Complexes.

While lanthanide (Ln) silylamide chemistry is mature, the corresponding silylphosphide chemistry is underdeveloped, with [Sm{P(SiMe3)2}{μ-P(SiMe3)2}3Sm(THF)3] being the sole example of a structurally authenticated Ln(II) silylphosphide complex. Here, we expand the Ln(II) {P(SiMe3)2} chemistry through the synthesis and characterization of nine complexes. The dinuclear "ate" salt-occluded complexes [{Ln[P(SiMe3)2]3(THF)}2(μ-I)K3(THF)] (1-Ln; Ln = Sm, Eu) and polymeric "ate" complex [KYb{P(SiMe3)2}3{μ-K[P(SiMe3)2]}2]∞ (2-Yb) were prepared by the respective salt metathesis reactions of parent [LnI2(THF)2] (Ln = Sm, Eu, Yb) with 2 or 3 equiv of K{P(SiMe3)2} in diethyl ether. The separate treatment of these complexes with either pyridine or 18-crown-6 led to the formation of the mononuclear solvated adducts trans-[Ln{P(SiMe3)2}2(py)4] (3-Ln; Ln = Sm, Eu, Yb) and [Ln{P(SiMe3)2}2(18-crown-6)] (4-Ln; Ln = Sm, Eu, Yb), with concomitant loss of K{P(SiMe3)2}. The complexes were characterized by a combination of NMR, electron paramagnetic resonance (EPR), attenuated total reflectance infrared (ATR-IR), electronic absorption and emission spectroscopies, elemental analysis, SQUID magnetometry, and single crystal X-ray diffraction. We find that these complexes contrast with those of related Ln(II) bis(silyl)amide complexes due to differences in ligand donor atom hardness and ligand steric requirements from Ln-P bonds being longer than Ln-N bonds. This leads to higher coordination numbers, shorter luminescence lifetimes, and smaller easy-axis magnetic anisotropy parameters.

Coordination of Al(C6F5)3 vs. B(C6F5)3 on group 6 end-on dinitrogen complexes: chemical and structural divergences.

The coordination of the Lewis superacid tris(pentafluorophenyl)alane (AlCF) to phosphine-supported, group 6 bis(dinitrogen) complexes [ML2(N2)2] is explored, with M = Cr, Mo or W and L = dppe (1,2-bis(diphenylphosphino)ethane), depe (1,2-bis(diethylphosphino)ethane), dmpe (1,2-bis(dimethylphosphino)ethane) or 2 × PMe2Ph. Akin to tris(pentafluorophenyl)borane (BCF), AlCF can form 1 : 1 adducts by coordination to one distal nitrogen of general formula trans-[ML2(N2){(μ-η1:η1-N2)Al(C6F5)3}]. The boron and aluminium adducts are structurally similar, showing a comparable level of N2 push-pull activation. A notable exception is a bent (BCF adducts) vs. linear (AlCF adducts) M-N-N-LA motif (LA = Lewis acid), explained computationally as the result of steric repulsion. A striking difference arose when the formation of two-fold adducts was conducted. While in the case of BCF the 2 : 1 Lewis pairs could be observed in equilibrium with the 1 : 1 adduct and free borane but resisted isolation, AlCF forms robust 2 : 1 adducts trans-[ML2{(μ-η1:η1-N2)Al(C6F5)3}2] that isomerise into a more stable cis configuration. These compounds could be isolated and structurally characterized, and represent the first examples of trinuclear heterometallic complexes formed by Lewis acid-base interaction exhibiting p and d elements. Calculations also demonstrate that from the bare complex to the two-fold aluminium adduct, substantial decrease of the HOMO-LUMO gap is observed, and, unlike the trans adducts (1 : 1 and 1 : 2) for which the HOMO was computed to be a pure d orbital, the one of the cis-trinuclear compounds mixes a d orbital with a π* one of each N2 ligands. This may translate into a more favourable electrophilic attack on the N2 ligands instead of the metal centre, while a stabilized N2-centered LUMO should ease electron transfer, suggesting Lewis acids could be co-activators for electro-catalysed N2 reduction. Experimental UV-vis spectra for the tungsten family of compounds were compared with TD-DFT calculations (CAM-B3LYP/def2-TZVP), allowing to assign the low extinction bands found in the visible spectrum to unusual low-lying MLCT involving N2-centered orbitals. As significant red-shifts are observed upon LA coordination, this could have important implications for the development of visible light-driven nitrogen fixation.

Metal-Involving Halogen Bonding Confirmed Using DFT Calculations with Periodic Boundary Conditions

The cocrystallization of trans-[PtI2(NCN(CH2)5)2] and iodoform (CHI3) yields crystalline adduct trans-[PtI2(NCN(CH2)5)2]∙2CHI3, the structure of which was studied via single-crystal X-ray diffractometry (XRD). In the XRD structure of trans-[PtI2(NCN(CH2)5)2]∙2CHI3, apart from rather predictable C–H∙∙∙I hydrogen bonds (HBs) and C−I∙∙∙I halogen bonds (XBs) with the iodide ligands, we identified C–I∙∙∙Pt metal-involving XBs, where the platinum center functions as an XB acceptor (that includes a metal dz2-orbital) toward the σ-holes of I atoms of CHI3. DFT calculations (PBE-D3/jorge-TZP-DKH with plane waves in the GAPW method) were carried out in the CP2K program for isolated molecules, complex–iodoform clusters, and crystal models with periodic boundary conditions, where the noncovalent nature and the existence of the interactions were confirmed using charge analysis, Wiberg bond indexes, and QTAIM topology analysis of electron density, whereas the philicities of the noncovalent partners were proved using charge analysis, electron localization function, electron density deformation, and one-electron potential projections, as well as electron density/electrostatic potential profiles for cluster models and electrostatic potential surfaces (ρ = 0.001 a.u.) for isolated molecules.

Well‐defined Nickel P3C Complexes as Hydrogenation Catalysts of N‐Heteroarenes Under Mild Conditions

AbstractThe reactivity of metal complexes can be primarily controlled by their coordinating ligands. Electronic effects and geometric restrictions imposed by ligands, prototypically modify their reactivity, but are not always straightforward accessible. In the course of the study, we explored new C3‐symmetric organometallic nickel (II) complexes ((P3C)Ni)) with the particularity of having a metalated apical carbon trans to a labile coordination site readily available as a catalytic site. The synthetic methodology allowed to tune the electronic properties by introducing substituents on the phosphines. We studied the nature of the C−Ni bond by X‐ray absorption spectroscopy (XAS) and DFT and applied them to the catalytic hydrogenation of quinolines with a good chemical scope and group tolerance. 1H‐NMR monitoring, isotopic labelling, and computational studies are consistent with a heterolytic activation of the dihydrogen molecule after forming a σ‐H2 adduct trans to the metalated carbon.

Isomorphous Series of PdII-Containing Halogen-Bond Donors Exhibiting Cl/Br/I Triple Halogen Isostructural Exchange

Two isomorphous series including the adducts trans-[PdI2(CNC6H4-4-X)2]·2I2 [(1–3)·2I2; X = Cl 1, Br 2, I 3] and the complexes cis-[PdCl2(CNC6H4-4-X)(PPh3)] (4–6; X = Cl 4, Br 5, I 6) were characterized by X-ray crystallography. Inspection of the X-ray diffraction data allowed the identification of halogen-bonding C–X···I–I in (1–3)·2I2 and C–X···Cl–[Pd] in 4–6 thus providing a rare example of the triple Cl/Br/I exchange of σ-hole donating halogens. In accord with the conducted theoretical considerations, the strength of these XBs are in the range of 0.9–2.8 kcal/mol, and these contacts are of a noncovalent nature. The calculated maximum electrostatic potentials on the σ-hole donating X centers of CNC6H4-4-X on the 0.001 au molecular surfaces for both (1–3)·2I2 and 4–6 series are increased along with the decrease of relative XB lengths. These data are consistent with Politzer and co-workers conclusions that are based exclusively on theoretical ground.

One-pot synthesis of a PCsp3P-type pincer complex via double C[sbnd]H palladation of a large chelate ring

The diphosphine proligand R2P(CH2)5PR2 (R = i-Pr) reacts with PdCl2 or Pd(PhCN)2Cl2 in CH2Cl2 to give the 2:2 adduct trans-{µ-kP,kP′-R2P(CH2)5PR2}2Pd2Cl4 (1) featuring a 16-atom chelate ring, along with other uncharacterized species. Treating 1 with AgOTf or heating it in the solid state gave the PCsp3P-type pincer complexes {kP,kC,kP-(R2P(CH2)2)2CH}PdX (X: OTf, 2; Cl, 2-Cl). Complex 2 was also prepared via a one-pot route by refluxing a mixture of the proligand, PdCl2, and AgOTf in toluene. Complexes 1 and 2 have been characterized by NMR spectroscopy, elemental analysis, mass spectrometry and single crystal X-ray analysis.

Asymmetric Wacker-Type Oxyallenylation and Azaallenylation of Cyclic Alkenes.

Palladium-catalyzed three-component carboetherification of cyclic alkenes proceeded to give trans adducts exclusively with excellent enantioselectivity through a Wacker-type pathway. The reaction is also applicable to other oxygen nucleophiles, such as water, phenols, and carboxylic acids, as well as some electron-poor aryl amines.

Asymmetric Wacker‐Type Oxyallenylation and Azaallenylation of Cyclic Alkenes

AbstractPalladium‐catalyzed three‐component carboetherification of cyclic alkenes proceeded to give trans adducts exclusively with excellent enantioselectivity through a Wacker‐type pathway. The reaction is also applicable to other oxygen nucleophiles, such as water, phenols, and carboxylic acids, as well as some electron‐poor aryl amines.

Platinum complexes containing or derived from olefinic phosphines P(X)((CH2)6CH[dbnd]CH2)2 (X = OH, Ph, (CH2)6CH[dbnd]CH2); ring closing metatheses, structures, and trans/cis isomerizations

The reaction of (O)PH((CH2)6CHCH2)2 (2.0 equiv) and PtCl2 in toluene gives trans-PtCl2(P(OH)((CH2)6CHCH2)2)2 in 68% yield as a 82:18 mixture of Pt–Cl⋯H–OP hydrogen bond isomers. Addition of Grubbs’ first generation catalyst followed by hydrogenation (5 bar, cat. RhCl(PPh3)3 or PtO2) affords the doubly trans spanning macrocyclic diphosphine adduct trans-▪ (31–9% crude yields). A crystal structure shows that the two OH groups are anti, and hydrogen bond to opposite Cl–Pt–Cl chlorine atoms. The reaction of P(Ph)((CH2)6CHCH2)2 (2.0 equiv) and PtCl2 in toluene gives cis-PtCl2(P(Ph)((CH2)6CHCH2)2)2 (cis-5, 40%) and trans-5 (8%). The crystal structure of the former is determined. The trans/cis equilibrium ratios of these and related complexes are probed by DFT. Attempts to crystallize trans-▪ (trans-7′), which is a minor product from a published metathesis/hydrogenation sequence involving trans-PtCl2(P((CH2)6CHCH2)3)2, give only cis-7′, as established by 31P NMR and crystallography.

Origin of the Base‐Dependent Facial Selectivity in Annulation Reactions of Nazarov‐Type Reagents with Unsaturated Indolo[2,3‐a]quinolizidine Lactams

Methyl‐substituted Nazarov reagent 4 reacts stereoselectively with Nind‐Boc indoloquinolizidine lactams to give the expected 3‐H/15‐H cis pentacyclic yohimbine‐type adducts when using 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as the base. However, a dramatic change of the facial selectivity was observed when the reaction was performed in the presence of Cs2CO3, leading to the corresponding trans adducts. This annulation is the key step of a stereocontrolled synthesis of the 17a‐carba analogue of the heteroyohimbine alkaloid akuammigine. Theoretical calculations were used to rationalize the facial selectivity of these double Michael addition reactions.

Domino Synthesis of Embelin Derivatives with Antibacterial Activity.

A series of dihydropyran embelin derivatives was synthesized through a direct and highly efficient approach based on a domino Knoevenagel intramolecular hetero-Diels-Alder reaction from natural embelin (1), using unsaturated aldehydes in the presence of organocatalysts such as ethylendiamine diacetate or l-proline. The aliphatic aldehydes yielded exclusively trans adducts, while mixtures of trans and cis isomers were found in reactions with aromatic aldehydes, with the cis form always predominating. Some of the compounds obtained were active and selective against Gram-positive bacteria, including multiresistant Staphylococcus aureus clinical isolates.

Synthesis of Mitomycin C and Decarbamoylmitomycin C N2 deoxyguanosine-adducts

Mitomycin C (MC) and Decarbamoylmitomycin C (DMC) – a derivative of MC lacking the carbamate on C10 – are DNA alkylating agents. Their cytotoxicity is attributed to their ability to generate DNA monoadducts as well as intrastrand and interstrand cross-links (ICLs). The major monoadducts generated by MC and DMC in tumor cells have opposite stereochemistry at carbon one of the guanine–mitosene bond: trans (or alpha) for MC and cis (or beta) for DMC. We hypothesize that local disruptions of DNA structure from trans or cis adducts are responsible for the different biochemical responses produced by MC and DMC. Access to DNA substrates bearing cis and trans MC/DMC lesions is essential to verify this hypothesis. Synthetic oligonucleotides bearing trans lesions can be obtained by bio-mimetic methods. However, this approach does not yield cis adducts. This report presents the first chemical synthesis of a cis mitosene DNA adduct. We also examined the stereopreference exhibited by the two drugs at the mononucleotide level by analyzing the formation of cis and trans adducts in the reaction of deoxyguanosine with MC or DMC using a variety of activation conditions. In addition, we performed Density Functional Theory calculations to evaluate the energies of these reactions. Direct alkylation under autocatalytic or bifunctional conditions yielded preferentially alpha adducts with both MC and DMC. DFT calculations showed that under bifunctional activation, the thermodynamically favored adducts are alpha, trans, for MC and beta, cis, for DMC. This suggests that the duplex DNA structure may stabilize/oriente the activated pro-drugs so that, with DMC, formation of the thermodynamically favored beta products are possible in a cellular environment.

Enhanced asymmetric photocycloaddition of anthracene tethered to maleate versus fumarate through non-fluorescent exciplex intermediate

The asymmetric photocycloaddition of anthracene-tethered maleate with a small (S)-1-methylpropyl auxiliary at the peripheral position (1Z) underwent much faster than that of the corresponding fumarate (1E). The absolute configuration of the newly created chiral center in the major product was ambiguously assigned as (4S) by X-ray crystallographic as well as CD spectral studies. The facile E–Z photoisomerization was simultaneously observed for both 1Z and 1E, again much faster for 1Z. The concurrent electron transfer works as a quenching process and the fumarate acted as a better quencher than maleate in both intramolecular and intermolecular systems. The fluorescence quenching and quantum yield investigations also supported such facile electron transfer from excited-state anthracene to acceptor in the singlet manifold. Observed diastereoselectivities in the photocycloaddition of 1Z and 1E were moderate but substantial (5–12% de), given the fact that the chiral auxiliary is introduced at the remote position from the reaction center (4-bond separation). The non-fluorescent exciplex, probably in a triplet manifold derived from the singlet exciplex, plays a crucial role in this efficient cyclization process, affording a biradical intermediate, that can either dissociate or undergo second bond formation to afford a diastereomeric trans adduct 2. The diastereoselectivity was higher in less polar solvents, suggesting the polar nature of the exciplex.

Stereocontrolled Annulations of Indolo[2,3‐a]quinolizidine‐Derived Lactams with a Silylated Nazarov Reagent: Access to Allo and Epiallo Yohimbine‐Type Derivatives

The facial selectivity of double Michael addition reactions of the silylated Nazarov reagent 4 to unsaturated indolo[2,3-a]quinolizidine lactams 3 has been studied. Pentacyclic 3-H/15-H trans adducts 5 are generated from Nind -unsubstituted lactams, but the corresponding cis isomers 6 are formed when the indole nitrogen has a tert-butyloxycarbonyl (Boc) substituent. This reversal in the facial selectivity of the annulation has been rationalized by means of theoretical calculations, which indicate that the initial nucleophilic attack under stereoelectronic control is hampered by the presence of the bulky Boc group. The synthetic usefulness of the pentacyclic Nazarov-derived adducts is demonstrated by their conversion into allo and epiallo yohimbine-type targets.

Steric hindrances to the cycloaddition of (Z)-1-arylmethylidene-5,5-dimethyl-3-oxopyrazolidin-1-ium-2-ides to N-arylmaleimides

Sterically hindered cycloaddition of (Z)-1-arylmethylidene-5,5-dimethyl-3-oxopyrazolidin-1-ium-2-ides to 4-mono- and 2,6-disubstituted N-arylmaleimides requires prolonged heating (40–60 h) at ~150–155°C and yields mixtures of diastereoisomeric cycloadducts. The observed diastereoselectivity is determined by both electronic and steric interactions, depending on the nature and position of substituents in the azomethine imine and maleimide. The reactions of (Z)-1-(2,6-dichlorobenzylidene)-5,5-dimethyl-3-oxopyrazolidin-1-ium-2-ide with 4-substituted N-arylmaleimides give mainly the corresponding cis adducts as a result of preferential exo attack by the dipolarophile, whereas trans adducts predominate in the cycloaddition of (Z)-1-(4-X-benzylidene)-5,5-dimethyl-3-oxopyrazolidin-1-ium-2-ide and (Z)-1-(2,6-dichlorobenzylidene)-5,5-dimethyl-3-oxopyrazolidin- 1-ium-2-ide to 2,6-disubstituted N-arylmaleimides.

Platinum oxoboryl complexes as substrates for the formation of 1:1, 1:2, and 2:1 Lewis acid-base adducts and 1,2-dipolar additions.

The oxoboryl complex trans-[(Cy3 P)2 BrPt(B≡O)] (2) reacts with the Group 13 Lewis acids EBr3 (E=Al, Ga, In) to form the 1:1 Lewis acid-base adducts trans-[(Cy3 P)2 BrPt(B≡OEBr3 )] (6-8). This reactivity can be extended by using two equivalents of the respective Lewis acid EBr3 (E=Al, Ga) to form the 2:1 Lewis acid-base adducts trans-[(Cy3 P)2 (Br3 Al-Br)Pt(B≡OAlBr3 )] (18) and trans-[(Cy3 P)2 (Br3 Ga-Br)Pt(B≡OGaBr3 )] (15). Another reactivity pattern was demonstrated by coordinating two oxoboryl complexes 2 to InBr3 , forming the 1:2 Lewis acid-base adduct trans-[{(Cy3 P)2 BrPt(B≡O)}2 InBr3 ] (20). It was also possible to functionalize the B≡O triple bond itself. Trimethylsilylisothiocyanate reacts with 2 in a 1,2-dipolar addition to form the boryl complex trans-[(Cy3 P)2 BrPt{B(NCS)(OSiMe3 )}] (27).

Interactions between anticancer trans-platinum compounds and proteins: crystal structures and ESI-MS spectra of two protein adducts of trans-(dimethylamino)(methylamino)dichloridoplatinum(II).

The adducts formed between trans-(dimethylamino)(methylamino)dichloridoplatinum(II), [t-PtCl2(dma)(ma)], and two model proteins, i.e., hen egg white lysozyme and bovine pancreatic ribonuclease, were independently characterized by X-ray crystallography and electrospray ionization mass spectrometry. In these adducts, the Pt(II) center, upon chloride release, coordinates either to histidine or aspartic acid residues while both alkylamino ligands remain bound to the metal. Comparison with the cisplatin derivatives of the same proteins highlights for [t-PtCl2(dma)(ma)] a kind of biomolecular metalation remarkably different from that of cisplatin.

Non-covalent interactions of the carcinogen (+)-anti-BPDE with exon 1 of the human K-ras proto-oncogene

Investigating the complementary, but different, effects of physical (non-covalent) and chemical (covalent) mutagen-DNA and carcinogen-DNA interactions is important for understanding possible mechanisms of development and prevention of mutagenesis and carcinogenesis. A highly mutagenic and carcinogenic metabolite of the polycyclic aromatic hydrocarbon benzo[α]pyrene, namely (+)-anti-BPDE, is known to undergo both physical and chemical complexation with DNA. Previous studies of BPDE-DNA complex formation have focused on processes that require substantial structural reorganization, such as intercalation, and consequently relatively long time scales. However, some initial processes which occur within shorter time scales, such as external non-covalent binding, and which do not require major DNA structural reorganization have not been thoroughly investigated. A detailed computational study of such initial BPDE-DNA interactions is needed to elucidate the temporal and structural origins of the major covalent adduct, a promutagenic, which is known to exist in an external (+)-trans-anti-BPDE-N(2)-dGuanosine configuration. Accordingly, the initial stages of external non-covalent BPDE-DNA binding are studied in this work as well as their relationship to subsequent formation of the major, also external, covalent adduct. To study mechanisms that occur prior to extensive DNA structural reorganization, we present a first and detailed codon by codon computational study of the non-covalent interactions of (+)-anti-BPDE with DNA. In particular, due to its relevance to carcinogenesis, the interaction of (+)-anti-BPDE with exon 1 of the human K-ras gene has been studied. External solvent-exposed non-covalent binding sites have been found which may be precursors of the major external trans adduct and, importantly, are located in codons 12 and 13 of the K-ras gene which are known to be key mutation hotspots. In addition, our study explains and correctly predicts preferential (+)-anti-BPDE binding at minor groove guanosines. A subtle combination of van der Waals and hydrogen bonding interactions has been found to be a primary factor in preferentially positioning (+)-anti-BPDE toward the 5' position of a guanosine's strand, consistent with proton NMR observations for the major trans adduct, and at 5'-TGG-3' sequences which are known to yield high binding probability.

Synthesis of Enantiopure 5-Substituted 2,3-Methanopyrrolidines by Cyclization of Enantiopure α-Branched α-N-Homoallylamino Nitriles

The preparation of 5-substituted 2,3-methanopyrro- lidines by the stereoselective cyclization of zincated α-amino ni- triles derived from enantiopure α-branched homoallylamines has been investigated. The formation of trans adducts in excellent dia- stereoselectivities (up to >98:2) and good yields (up to 71%) is ob- served. The absolute configuration and enantiomeric excess are dependent on the nitrogen protecting group. 2,3-Methanopyrrolidines {2-azabicyclo(3.1.0)hexane de- rivatives} are interesting molecules that have attracted in- terest both for their use as scaffolds in biologically active peptide mimics 1,2 and as synthetic intermediates for nitro- gen-containing compounds. 3 In contrast with the prepara- tion of 2,3-methanopyrrolidines in racemic form, 1a,3,4 general synthetic methods for the preparation of enantio- pure 2,3-methanopyrrolidines are not common. 1b-e,5-7

Stable azomethine imines derived from pyrazolidin-3-one and their cycloaddition to N-arylmaleimides

Reactions of (Z)-1-arylmethylidene-3-oxopyrazolidin-1-ium-2-ides (stable analogs of azomethine imines generated by thermal opening of the diaziridine fragment in 6-aryl-1,5-diazabicyclo[3.1.0]hexanes) with N-arylmaleimides having no ortho substituents in the aryl group are stereoselective: the products are mixtures of the corresponding cis and trans adducts, the latter prevailing (∼1.4–2.6: 1). trans Adducts are formed as the only products in the reactions with di-ortho-substituted N-arylmaleimides. (Z)-1-[(2,6-Dichlorophenyl) methylidene]-3-oxopyrazolidin-1-ium-2-ide reacts with both para- and ortho-substituted N-arylmaleimides to give exclusively trans adducts. Labile azomethine imines generated by thermolysis of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes are likely to have Z configuration as well.