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Terminally dilithiated tetramethylethylenediamine (TMEDA), LiCH2N(Me)CH2CH2N(Me)CH2Li (1), was prepared by transmetalation from Me3SnCH2N(Me)CH2CH2N(Me)CH2SnMe3 and n-BuLi. It was isolated as a highly air-sensitive white powder and was characterized by elemental analysis and by further transmetalation reactions. Compound 1 was used as a difunctional aminomethylating agent and reacted with R2MCl (R = Me, t-Bu; M = Al, Ga, In) to give the selective formation of 1,2,2,4,5,5-hexamethyl-1,4-diaza-2,5-dimetallabicyclo[2.2.2]octane (M = Al (2), Ga (3), In (4)) and 2,2,5,5-tetra-tert-butyl-1,4-dimethyl-1,4-diaza-2,5-dimetallabicyclo[2.2.2]octane (M = Al (5), Ga (6)) by simultaneous formation of two metal−carbon and two dative metal−nitrogen bonds accompanied by two ring closures. Compounds 2−6 were characterized by elemental analyses, by NMR spectroscopy (¹H, ¹³C, ²⁷Al), and by crystal structure determinations. The 1,4-diazabicyclo[2.2.2]octane-like structure is favored over potential isomers containing three-membered rings and over polymeric aggregation. Despite the high steric demand of the tert-butyl groups, this conformation persists even in the case of 5 and 6.

A series of C1-bridged Cp/amido group 4 metal complexes [(“CpCN”)MX2] was prepared. The starting compound 6-tert-butylfulvene (7) was reacted with LiNHR (R = o-anisyl (a), p-anisyl (b), phenyl (c), or tert-butyl (d)) to yield the Li(C5H4-CH(tBu)-NHR) compounds (8). Subsequent deprotonation with n-butyllithium, followed by transmetalation with Cl2Ti(NMe2)2, yielded the (“CpCN”)Ti(NR2)2 complexes 10 (a−d). A second synthetic series started from 6-(dimethylamino)fulvene (11). The reaction with the LiNHR reagents led to addition followed by HNMe2 elimination to yield the respective imino-substituted cyclopentadienides Li(C5H4-CH&dbd;NR) (13). Addition of methyllithium to 13 gave the (Li⁺)2(C5H4-CHMe-NR)^2-, (“CpCN”)^2-, ligands (14). Transmetalation with Cl2Ti(NMe2)2 subsequently yielded the corresponding μ-CHMe-bridged Cp/amido group 4 complexes 15 (a−c). Treatment with Me2SiCl2 cleanly converted the (“CpCN”)M(NR2)2 complexes to the respective (“CpCN”)MCl2 systems [3a−d, 4a−c (Ti), 5a (Zr)]. These were transformed to the (“CpCN”)M(CH3)2 complexes [μ-CHCMe3:  17a−d (Ti), 19a (Zr), μ-CHMe:  18a−c (Ti)] and the (s-cis-supine-η⁴-butadiene)(“CpCN”)Ti systems 21a−d and 22b,c. With respect to X-ray structure analyses the (CpCN)MX2 systems must be regarded as more “constrained” than their (“CpSiN”)MX2 analogues. The (“CpCN”)MCl2 and (“CpCN”)M(CH3)2 complexes were used as catalysts for ethene homopolymerization and ethene/1-octene copolymerization. All systems gave active catalysts, but these were quite different in their catalytic performance when compared with the usually applied (“CpSiN”)TiX2-derived catalysts. The (“CpCN”)M catalyst activities and selectivities were very dependent on the specific activator components employed.

The zirconacyclocumulenes 1a (R = CH3) and 1b (R = Ph) were prepared by isomerization of bis(propynyl)ZrCp2 or bis(phenylethynyl)ZrCp2, respectively, catalyzed by B(C6F5)3 (6 mol %). The compounds 1 added PCl3, PhPCl2, or Ph2PCl with cleavage of only one zirconium−carbon single bond. Chloride was added to zirconium and the remaining −PCl2, −P(Ph)Cl, or −PPh2 moiety attached at the distal β-carbon atom of the strained ZrC4R2 metallacycle to yield the respective ring-opened Zr/P-substituted enyne systems (5−7). The complexes 7a and 7b (both with −PPh2) and 6b (with −P(Ph)Cl) were characterized by X-ray diffraction.

Upon treatment with lithiumorganic nucleophiles, trans-configured oxiranyl carbaldimines are transformed into anti-configured cis-aziridinyl alcohols with excellent diastereoselectivity. This conversion may be explained by a new type of the aza-Payne rearrangement, including first a nucleophilic attack on the imine carbon atom with diastereofacial differentiation followed by an intramolecular nucleophilic opening of the oxiranyl ring with simultaneous formation of the aziridine ring.

The reaction of (C5H4−PPh2)2Zr(CH3)2 (5a) with HRh(CO)(PPh3)3 (6) leads to methane evolution and the formation of the early−late heterobimetallic complex [(μ-C5H4−PPh2)2(H3C−Zr−Rh(CO)PPh3)] (7a), which was characterized by X-ray diffraction (d(Zr−Rh) = 2.863(1) Å). The analogous dialkylphosphino-substituted complexes (C5H4−PR2)2Zr(CH3)2 (5b, R = isopropyl; 5c, R = cyclohexyl) react with the hydrido−rhodium reagent 6 to initially form the analogous bimetallic (Zr−Rh) complexes 7b,c, respectively. However, these complexes are not stable at ambient temperature in toluene solution, due to an equilibration with the products [(μ-C5H4−PR2)2(μ-CH3−Zr−Rh(PPh3))] (11) and [(μ-C5H4−PR2)2(H3C−Zr−Rh(CO)2)] (10). Treatment of the initially formed complexes 7b,c with carbon monoxide rapidly leads to the formation of the H3C(Zr−Rh)−dicarbonyl complexes 10b,c. The product 10c was characterized by X-ray crystal structure analysis. The systems 7b,c are not stable in dichloromethane. They react readily with the solvent by abstraction of two chlorine atoms to yield the compounds [(μ-C5H4−PR2)2(μ-O&dbd;C(CH3))(Cl−Zr−Rh−Cl)] (12b,c). Both products were characterized by X-ray diffraction. A cooperative action of the involved metals is assumed to account for the observed reactions at the intact heterobimetallic Zr−Rh framework.

N,N-Diisopropylaminomethyllithium (1) was prepared by transmetalation from Me3SnCH2NⁱPr2 and n-BuLi. It was characterized by NMR spectroscopy (¹H, ¹³C, ⁷Li). Compound 1 crystallizes as a hexamer (LiCH2NⁱPr2)6 and allowed the determination of the first solvent-free structure of an α-lithiated amine. It contains a Li6 core (distorted octahedron) 6-fold capped by CH2NⁱPr2 units. 1 is very sensitive to air-oxidation. A partially [(LiCH2NⁱPr2)4(LiOCH2NⁱPr2)2 (2)] and a completely oxidized [(LiOCH2NⁱPr2)6 (3)] cluster compound could be isolated. 2 and 3 were characterized by multinuclear NMR spectroscopy and by single-crystal X-ray diffraction. The results show that the hexameric structure is retained upon partial or complete oxidation. 1 was used as aminomethylating agent and reacted with Me2AlCl and Me2GaCl to give the aminomethylaluminum and -gallium compounds (Me2MCH2NⁱPr2)2 (M = Al, Ga), which are dimers containing six-membered rings. They were characterized by elemental analyses, NMR spectroscopy, and crystal structure determinations. They are present as dimers containing six-membered M2C2N2 rings in solution and in the solid state.

Estrogenicity-directed fractionation of a methanol extract of the strobiles of Humulus lupulus that had been extracted previously with supercritical CO2, known as “spent hops”, led to the isolation and identification of 22 compounds including 12 prenylated chalcones (1−8, 10−13), five prenylflavanones (14−17), 4-hydroxybenzaldehyde (18), sitosterol-3-O-β-glucopyranoside (19), humulinone (20), and cohumulinone (21). In addition, the prenylated chalcone xanthohumol C (9a) was obtained as a 6:1 mixture along with its 1‘ ‘,2‘ ‘-dihydro derivative (9b). Three new chalcones (4, 11, 12) and four previously unreported constituents of hops (5, 6, 9b, 13) are reported. The structures of the new compounds were determined through a combination of spectrometric techniques including 1D and 2D NMR, HRESIMS, and ESIMS-MS. Full ¹H NMR spin system analyses were performed to characterize the higher-order glucopyranosyl, prenyl, and chalcone B-ring spectra of the isolates. The principle estrogen 8-prenylnaringenin (15) from hops is an artifact formed along with its positional isomer 6-prenylnaringenin (16) through the spontaneous isomerization of the pro-estrogenic chalcone DMX (7).

A series of para-substituted diastereopure cis- and trans-2-fluoro-2-arylcyclopropylamines were synthesized and these were investigated as inhibitors of microbial tyramine oxidase from Arthrobacter sp. All compounds were shown to be competitive inhibitors of this enzyme. The nature of the para-substituents in the more potent trans-isomer (cis-relationship between fluorine and the amino group) of 2-fluoro-2-arylcyclopropylamine influenced the inhibitory potency in a consistent fashion. Thus, electron-withdrawing groups (F, Cl) slightly decreased the activity, while the methyl group (+ I substituent) increased the activity by a factor of ca. 7 compared to trans-2-fluoro-2-phenylcyclopropylamine and by a factor of 90 compared to tranylcypromine. Activity also was strongly dependent on the absolute configuration. The (1S,2S)-enantiomer of 2-fluoro-2-phenylcyclopropylamine was an excellent inhibitor of tyramine oxidase whereas the (1R,2R)-enantiomer was essentially devoid of activity.

The rearrangement of the carbamoyl group in allenyl carbamate 1 in the presence of n-BuLi in situ generates the allenolate 3, which is subsequently intercepted with aromatic aldehydes furnishing (Z)- or (E)-configured Baylis−Hillman-type adducts 4 or 5. The double bond isomers can be interconverted by a retro aldol-type reaction.

An overall stereoconservative protection and deprotection method of amino and carboxyl groups is presented. N-Phthaloyl N‘-alkyl secondary amides of α-amino acids can be generated from corresponding N-phthaloyl amino acids by coupling reaction of N-alkylamines using mixed anhydride method. These secondary amides can be transformed by thermal rearrangement of intermediate nitrosoamides to O-alkyl esters with retention of configuration and excellent yields.

1-Trimethylsilyl-1-alkenyl carbamates 1 are deprotonated by n-butyllithium/(−)-sparteine (2) with a high degree of enantiotopic differentiation in the γ-position to form the enantiomerically enriched allyllithium derivatives 3. Trapping these with several electrophiles proceeds stereospecifically in an anti-SE‘ or syn-SE‘ substitution to form products 4 or ent-4, respectively. Compounds 3a (R = Me) and 3b (R = Ph) exhibit toward carbonyl electrophiles opposite senses of almost complete stereospecificity, thus for 3b·2 the involvement of a η³-complex is suggested.

Treatment of the dimethylamino-[3]ferrocenophane 1a with B(C6F5)3 results in hydride abstraction at the −CH(NMe2) moiety in α-position to the ferrocene nucleus to yield the corresponding cation 4a. The X-ray crystal structure analysis of the salt 4a·[HO{B(C6F5)3}2^-] has revealed a residual Fe−Cα interaction even in this case of a strongly substituent-stabilized α-ferrocenyl carbenium ion. A DFT calculation of a series of derivatives containing nitrogen substituents of a decreasing ability for carbenium ion stabilization (4a, −NMe2; 4b, −pyrrolyl; 4c, −triazolyl) revealed a markedly increased Fe−C interaction with decreasing C⁺ stabilization by the hetarene substituents.

Treatment of 1,1‘-diacetylferrocene (1) with dimethylamine, catalyzed by titanium tetrachloride, proceeded in a Mannich-type C−C coupling reaction to yield the unsaturated [3]ferrocenophane 2. Subsequent catalytic hydrogenation gave the saturated [3]ferrocenophane derivative [(C5H4CHMeCH2CH(NMe2)C5H4)Fe] (trans-3). Directed Cp metalation of trans-3 was carried out by treatment with n-BuLi, followed by reaction with ClPPh2 to yield the “ortho-phosphorylated” P,N-[3]ferrocenophane chelate ligand 4. Its treatment with HPPh2 in acetic acid resulted in a clean substitution of the −NMe2 group by −PPh2 with overall stereochemical retention to yield the P,P-[3]ferrocenophane ligand 5. The stereochemical pathway of such substitution reactions at the [3]ferrocenophane framework, which proceed cleanly by a double-inversion route with participation of the metal center, was modeled by computational chemistry and its reactive cationic intermediate 14 characterized by a DFT calculation. Reaction of 4 with (cod)PdCl2 gave the chelate complex 6. The analogous reaction of 5 with (cod)PdCl2 furnished the P,P-[3]ferrocenophane−PdCl2 chelate complex 7. Both the complexes 6 and 7 and the ligand 5 were characterized by X-ray diffraction. Treatment of 7 with AgBF4 in dichloromethane or alternatively of 5 with palladium acetate, followed by BF3 addition, gave very active catalyst systems for alternating carbon monoxide/ethene copolymerization.

Treatment of 6-(dimethylamino)-6-methylpentafulvene (2a) with methyllithium in ether at −40 °C leads to CH3 addition to the C6-fulvene carbon atom to yield the [C5H4−CMe2−NMe2]Li reagent 3a, whereas treatment of 2a with MeLi in THF at −78 °C results in deprotonation with formation of [C5H4−C(&dbd;CH2)−NMe2]Li (4a). In contrast, treatment of 6-diethylamino-6-methylfulvene (2b) with methyllithium under any of these conditions leads only to H⁺-abstraction to give [C5H4−C(&dbd;CH2)−NEt2]Li (4b). Treatment of the reagents 4 with CpZrCl3 yields the enamino-Cp-substituted bent metallocenes [η⁵-C5H4−C(&dbd;CH2)−NR2]CpZrCl2 5a (R = CH3) and 5b (R = C2H5), respectively. Analogous treatment of 4b with zirconium tetrachloride gave the doubly functionalized zirconocene complex [η⁵-C5H4−C(&dbd;CH2)−NEt2]2ZrCl2 (6b). The complexes 5a, 5b, and 6b were characterized by X-ray diffraction. Treatment of 3a with CpZrCl3 gave [η⁵-C5H4−CMe2−NMe2]CpZrCl2 (8a); the analogous reaction with ZrCl4 gave [η⁵-C5H4−CMe2−NMe2]2ZrCl2 (8b). Both complexes 8 reacted with (butadiene)magnesium with replacement of both chloride ligands at zirconium. The probably generated (η⁴-butadiene)zirconocene complexes were, however, not stable under the applied reaction conditions, but reacted further by C−H activation at the N−CH3 group with intramolecular hydrogen transfer to the butadiene ligand to yield the cyclometalated products [η⁵-C5H4−CMe2− N(CH3)−CH2−]Zr(L)(CH2CHCHCH3) 13a (L = Cp) and 13b (L = [η⁵-C5H4−CMe2−NMe2]), respectively. Complex 5a reacts analogously with (butadiene)magnesium to yield the C−H activation product [η⁵-C5H4−C(&dbd;CH2)−N(CH3)−CH2−]ZrCp(CH2CHCHCH3) 14. The 1-diethylaminoethenyl-Cp-substituted systems 5b and 6b react differently with (butadiene)magnesium. They form the stable η⁴-butadiene complexes s-trans-15 and s-cis-15A/B (from 5b) and s-trans-17 and s-cis-17 (from 6b), respectively. [N]CH activation was not observed in these cases. Treatment of the cyclometalated products 13a, 14, and 15 with B(C6F5)3 gave active homogeneous Ziegler−Natta catalysts for ethene polymerization, whereas the systems 13b/B(C6F5)3 and 17/B(C6F5)3 were close to inactive under comparable conditions.

Fischer carbene complexes were found to undergo Baylis−Hillman type additions to α,β-unsaturated acid amides. Reactions of (non-CH-acidic) carbene tungsten complexes 1a−c with (CH-acidic) but-2-enoic acid amides 2 in the presence of POCl3/Et3N resulted in an α-addition of the carbene ligand to the amide backbone and formation of cross-conjugated aminocarbene complexes 3. Reaction of CH-acidic carbene tungsten complexes 1d−h gave the cross-conjugated aminocarbene complexes 9 (which are double-bond isomers of compounds 3) together with (cyclobutenyl)carbene complexes 10, by α- and β-addition, respectively, to the but-2-enoic amides 2. Compounds 9 and 10 are valence isomers, but they do not interconvert thermally.

Double deprotonation of [(C5Me4H)−SiMe2−PH(cyclohexyl)] (4) was achieved by treatment with n-butyllithium in THF/pentane to afford the dianionic ligand [(C5Me4)-SiMe2−P(cyclohexyl)]^2- as its dilithio salt (5). The reagent 5 was transmetalated by subsequent treatment with [Cl2Ti(NMe2)2] (6a) to yield the dimethylsilanediyl-bridged Cp*/phosphido titanium complex [(C5Me4)−SiMe2−PCy]Ti(NMe2)2 (7a; 67% isolated yield). The analogous reaction of 5 with [Cl2Zr(NEt2)2(THF)2] (6b) gave [(C5Me4)−SiMe2−PCy]Zr(NEt2)2 (7b; isolated in 59% yield). Single crystals of the complexes 7a,b were obtained from pentane. The X-ray crystal structure analyses revealed distorted “constrained geometry” group 4 metal complex structures due to the presence of a chiral, nonplanar coordination geometry at the phosphorus atom. Complexes 7a,b both give active homogeneous Ziegler−Natta catalysts for ethene/1-octene copolymerization upon activation with excess methylalumoxane.

Treatment of [Cp2TiCH3(thf)⁺] (5, with [BPh4^-] anion) with 1,3-diisopropylimidazol-2-ylidene (4) at ambient temperature resulted in a rapid displacement of the thf ligand by the stable heterocyclic carbene to yield the Arduengo carbene methyltitanocene cation complex 6a (>90% isolated). The X-ray crystal structure analysis of 6a showed that the heteroatom-stabilized carbene ligand [d(Ti−C(carbene) = 2.289(2) Å, d(Ti−CH3) = 2.178(3) Å] was bonded to titanium in an orientation where the imidazol-2-ylidene ring lies in the major σ-ligand plane of the bent metallocene moiety. A DFT calculation of 6a and a series of related model compounds has revealed that the Arduengo carbene serves as a pure σ-donor ligand to the titanocene moiety. The observed favored “in-plane” orientation of the ligand is steric in origin. Consequently, complex 6a attains an analogous Cs-symmetric structure in solution, featuring symmetry-equivalent Cp rings and a pair of diastereotopic isopropyl substituents as well as chemically differentiated imidazol-2-ylidene C⁴H&dbd;C⁵H groups. The reaction of the ion pair [(Cp2ZrCH3)⁺(CH3B(C6F5)3^-] (7) with 4 gave the analogous Arduengo carbene zirconocene cation complex 6b (>95% isolated, with [CH3B(C6F5)3^-] anion).

Condensation of (ethoxy,methyl)carbene complexes (OC)5M&dbd;C(OEt)CH3 1a,b (M = W, Cr) with α,β-unsaturated secondary acid amides PhCH&dbd;CHC(&dbd;O)NHR 7a−c in the presence of POCl3/Et3N affords C-enamino carbene complexes (3Z)-3a−f (= 4-NH-amino-1-metalla-1,3,5-hexatrienes). A fundamental change of the reaction course was induced by an α-substituent of the carbene complex 1. Thus, (n-butyl,ethoxy)carbene complex 1c under similar conditions yields N-enamino carbene complexes 8h−l instead of C-enamino carbene complexes (Scheme 2). Formation of compounds 8 involves an unprecedented retro-Fischer reaction, by which the C,C bond between the α-carbon atom and the carbene carbon atom is broken under the influence of a β-imino functionality.

3-Aza-1-metallahexa-1,3,5-trienes 3a−f were obtained in good yields by condensation of the (NH2-amino)carbene complexes (CO)5M&dbd;C(Ph)NH2 (1a,b; M = Cr, W) with α,β-unsaturated acid amides 2 in the presence of phosphoryl chloride and triethylamine. Compounds 3 undergo a thermally induced π-cyclization to pyrroles 4.

4-Amino-1-tungsta-1,3,5-hexatrienes (CO)5W&dbd;C(OEt)CH&dbd;C(NR2)CH&dbd;CHPh (3E)-2 and (cyclohexan-4-on-1-yl)carbene tungsten complexes 6 were obtained by condensation of (ethoxy,methyl)carbene tungsten complex (OC)5W&dbd;C(OEt)CH3 1a with α,β-unsaturated tertiary acid amides PhCH&dbd;CHC(&dbd;O)NR2 7 in the presence of POCl3/Et3N and (COCl)2/Et3N, respectively. Compounds 2 underwent a π-cyclization to zwitterionic η¹-cyclopentadiene complexes 3. Condensation of (prim-alkyl,ethoxy)carbene complexes (CO)5M&dbd;C(OEt)CH2R¹ 1 (M = W, Cr; R¹ = c-C7H7, n-Pr) with compounds 7 afforded (cyclobutenyl)carbene complexes 9.

Increasing worldwide regulations require increased efforts toward validation of analytical and pharmacological reference materials. A detailed survey of glucoiberin, a prototype lead constituent of therapeutic value, using 1D/2D NMR, MS, and X-ray spectroscopy provided precise phytochemical data for structure assignment. Quantitative reference validation was achieved by the recently proposed qNMR method.

Addition of methyllithium or p-tolyllithium to the C-6 carbon atom of the lithium (N-phenylformimidoyl)cyclopentadienide reagent 5 resulted in the formation of the dianionic sp³-C1-alkylidene-bridged Cp/amido ligand systems [C5H4−CHR−NPh]^2- (6a, R = CH3; 6b, R = p-tolyl; each with Li⁺ cations). Transmetalation of 6a from lithium to zirconium was achieved by treatment with ZrCl4(THF)2 (7a) to yield the metallacyclic sp³-C1-linked spiro constrained geometry complex (η⁵-C5H4−CHMe−NPh-κN)2Zr (2a). Treatment of 6a with Cl2Ti(NMe2)2 (7c) gave the alkylidene-bridged Cp/amido titanium complex (η⁵-C5H4−CHMe−NPh-κN)Zr(NMe2)2 (2b). Analogous treatment of Cl2Zr(NEt2)2(THF)2 (7b) with 6a or 6b furnished the related (CpCN)Zr complexes (C5H4−CHR−NPh)Zr(NEt2)2 (2c, R = CH3; 2d, R = p-tolyl) each in ≥70% yield. The complexes 2a and 2b were both characterized by X-ray crystal structure analyses. The observation that both exhibit Cp(centroid)−M−N angles that are by ca. 10° smaller than those of their respective dimethylsilanediyl-bridged analogues renders the CpCN group metal complexes as more constrained than their conventional (Cp*SiN)M analogues. Lithium 4-methylanilide adds to the C-6 carbon atom of the non-CH-acidic pentafulvene (C5H4)&dbd;CHCMe3 (13a) to yield Li[C5H4−CH(CMe3)(NH-p-tolyl)] (14a), which was subsequently NH-deprotonated by treatment with LDA to yield the dianionic reagent [C5H4−CH(CMe3)(N-p-tolyl)]^2- (6c, as the dilithium compound). Analogous addition of lithium tert-butylamide to 13a, followed by NH-deprotonation by treatment with tert-butyllithium, yielded Li2[C5H4−CH(NCMe3)CMe3] (6d). Lithium tert-butylamide added to 1,2,3,4-tetramethylpentafulvene (13b) to yield Li[C5Me4−CH2−NH(CMe3)] (14c), which was subsequently NH-deprotonated by treatment with tert-butyllithium to yield Li2[C5Me4−CH2N(CMe3)] (6e). Transmetalation of 6c by treatment with Cl2Ti(NMe2)2 (7c) or Cl2Zr(NEt2)2(THF)2 (7b) cleanly gave the respective CpCN group 4 metal complexes [C5H4−CH(CMe3)(N−p-tolyl)]M(NR2)2 (2e, M = Ti; 2f, M = Zr). Similarly, the sp³-C1-bridged “constrained geometry” system [C5H4−CH(CMe3)(NCMe3)]Zr(NEt2)2 (2g) was obtained in good yield (70%) from the reaction of 6d with 7b, and treatment of 6e with 7b furnished the (Cp*CN)Zr complex [C5Me4−CH2−N(CMe3)]Zr(NEt2)2 (2h, 65% isolated). Activation of the (CpCN)M(NR2)2 systems by treatment with a large excess of methylalumoxane in toluene solution gave homogeneous Ziegler−Natta catalysts for the polymerization of ethylene (carried out at 60 °C) and the copolymerization of ethene with 1-octene (at 90 °C).