Conformational Studies of (±)‐11,12‐Didehydro‐11‐deoxycorynoline and (+)‐11,13‐Didehydro‐11‐deoxychelidonine,Hexahydrobenzo[c]phenanthridine‐Type Alkaloid Derivatives,by X‐Ray Crystal Structure and NMR Analyses

The X‐ray crystal analyses of the two 11‐deoxy‐didehydrohexahydrobenzo[c]phenanthridine‐type alkaloid derivatives 3 and 4 , derived from (±)‐corynoline ( 1 ) and (+)‐chelidonine ( 2 ), established their structures as (±)‐(5bRS,12bRS)‐5b,12b,13,14‐tetrahydro‐5b,13‐dimethyl[1,3]benzodioxolo[5,6‐c]‐1,3‐dioxolo[4,5‐i]phenanthridine ( 3 ) and (+)‐rel‐(12bR)‐7,12b,13,14‐tetrahydro‐13‐methyl[1,3]benzodioxolo[5,6‐c]‐1,3‐dioxolo[4,5‐i]phenanthridine ( 4 ). The conformations of 3 and 4 in CDCl₃ were determined on the basis of ¹H‐ and ¹³C‐NMR spectroscopy.     

The Synthesis,Photophysical Characterization,and X‐Ray Structure Analysis of Two Polymorphs of 4,4′‐Diacetylstilbene

A palladium(II) acetate‐catalyzed synthesis of 1 that utilizes the novel triazene 1‐{4‐[(E)‐morpholin‐4‐yldiazenyl]phenyl}ethanone as a synthon is described. The room temperature absorption spectra of 1 in various solvents exhibited a π→π* transition in the range of 330–350 nm. Compound 1 was observed to be luminescent, with room‐temperature solution and solid‐state emission spectra that exhibited maxima in the range 400–500 nm. All room‐temperature absorption and emission spectra exhibited some degree of vibrational structure. The emission spectrum of 1 at 77 K in propanenitrile glass was broad and featureless with a maximum at 447 nm. Compound 1 crystallized as a yellow and colorless polymorph. X‐Ray structure analyses of both of these polymorphs and 1‐{4‐[(E)‐morpholin‐4‐yldiazenyl]phenyl}ethanone are presented.     

Palladium(II) Complexes of the Thiosemicarbazone and N‐Ethylthiosemicarbazone of 3‐Hydroxypyridine‐2‐carbaldehyde: Synthesis,Properties, and X‐Ray Crystal Structure

Two novel, stable Pd^II complexes, compounds 3 and 4 , of two 3‐hydroxypyridine‐2‐carbaldehyde thiosemicarbazones, 1 and 2 , resp., were prepared from Li₂PdCl₄. The single‐crystal X‐ray structure of complex 3 (= [Pd( 2 )Cl]) shows that the ligand monoanion coordinates in a planar conformation to the metal via the pyridyl N‐, the imine N‐, and the thiolato S‐atoms. Intermolecular H‐bonds, π–π, and CH ? ? ? π interactions lead to a two‐dimensional supramolecular assembly. The electronic, IR, UV/VIS, and NMR spectroscopic data of the two complexes are reported, together with their electrochemical properties. A sophisticated experimental procedure was used to determine the multiple dissociation constants of the ligands 1 and 2 by UV/VIS titration.     

Platinum(II) and Palladium(II) Halides and Pseudohalides with the Ligand Tri(1‐cyclohepta‐2, 4, 6‐trienyl)phosphane. X‐Ray Structural Analysis of [P(C7H7)2(η2‐C7H7)]PtI2

Tri(1‐cyclohepta‐2, 4, 6‐trienyl)phosphane, P(C₇H₇)₃ ( 1 ) ([P] when coordinated to a metal) stabilizes platinum(II) ( 2 ) and palladium(II) dihalides ( 3 ) as [P]MX₂ with X = Cl ( a ), Br ( b ) and I ( c ). The phosphane coordinates to the metal as a chelate ligand via both phosphorus and the central η²‐C=C bond of one of the cyclohepta‐2, 4, 6‐trienyl rings. The complexes were prepared by various routes, mainly by the reaction of (cod)MCl₂ (cod = cycloocta‐1, 5‐diene) with 1 to give the chlorides 2a and 3a , which then could be converted into the bromides 2b , 3b or the iodides 2c , 3c by reaction with NaBr or NaI, respectively. The molecular structure of 2c was determined by X‐ray analysis. Treatment of 2a and 3a with sodium or potassium salts of several pseudohalides afforded the complexes [P]MX₂ 2d (NCO/NCO), 2e₁ (NCS/SCN), 2e₁' (SCN/NCS), 2f₂ (SeCN/SeCN), 3f₁ (NCSe/SeCN), 2g and 3g (X = N₃). Attempts failed to synthesize the cyanides 2h and 3h by the same route. By using an excess of trimethylsilyl cyanide in the reaction with 2a in THF solution, the complex trans‐{[(C₇H₇)₃P]₂Pt(CN)₂} ( 4h ) was obtained instead of 2h . The analogous complexes trans‐{[(C₇H₇)₃P]₂MX₂} with M = Pt ( 4 ) and Pd ( 5 ) for X = Cl ( a ), Br ( b ), I ( c ) could be prepared from the reaction of the corresponding tetrahalogenometallates and 1 (in the case of 5c from PdI₂ and 1 ). In contrast to 4h , the complexes 4a‐c and 5a‐c were found to be labile in solution with respect to partial loss of the phosphane 1 and rearrangement into 2a‐c and 3a‐c , respectively. All compounds were characterized by IR spectroscopy and by multinuclear magnetic resonance spectroscopy (¹H, ¹³C, ³¹P, ⁷⁷Se and ¹⁹⁵Pt NMR). The ligand [P] in 2 and 3 is fluxional with regard to coordination of the C₇H₇ rings to the metal.     

Efficient One‐Pot Synthesis of Alkyl 2‐(Dialkylamino)‐4‐phenylthiazole‐5‐carboxylates and Single‐Crystal X‐Ray Structure of Methyl 2‐(Diisopropylamino)‐4‐phenylthiazole‐5‐carboxylate

The reaction between secondary amines, benzoyl isothiocyanate, and dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) in the presence of silica gel (SiO₂) led to alkyl 2‐(dialkylamino)‐4‐phenylthiazole‐5‐carboxylates in fairly high yields. The structures of the products were confirmed by their IR, ¹H‐ and ¹³C‐NMR, and mass spectra, and by a single‐crystal X‐ray structure determination.     

cis‐trans Peptide‐Bond Isomerization in α‐Methylproline Derivatives

α‐Methyl‐L ‐proline is an α‐substituted analog of proline that has been previously employed to constrain prolyl peptide bonds in a trans conformation. Here, we revisit the cis‐trans prolyl peptide bond equilibrium in derivatives of α‐methyl‐L ‐proline, such as N‐Boc‐protected α‐methyl‐L ‐proline and the hexapeptide H‐Ala‐Tyr‐αMePro‐Tyr‐Asp‐Val‐OH. In Boc‐α‐methyl‐L ‐proline, we found that both cis and trans conformers were populated, whereas, in the short peptide, only the trans conformer was detected. The energy barrier for the cis‐trans isomerization in Boc‐α‐methyl‐L ‐proline was determined by line‐shape analysis of NMR spectra obtained at different temperatures and found to be 1.24 kcal/mol (at 298 K) higher than the corresponding value for Boc‐L ‐proline. These findings further illuminate the conformationally constraining properties of α‐methyl‐L ‐proline.     

The Structures of Indazolin‐3‐one (=1,2‐Dihydro‐3H‐indazol‐3‐one) and 7‐Nitroindazolin‐3‐one

The existence of polymorphism in parent indazolin‐3‐one (=1,2‐dihydro‐3H‐indazol‐3‐one; 1 ) is reported as well as an X‐ray and NMR CPMAS study establishing that its 7‐nitro derivative 2 exists as the 3‐hydroxy tautomer. Absolute shieldings calculated at the GIAO/B3LYP/6‐311++G(d,p) level were used to determine the tautomeric oxo/hydroxy equilibrium in solution, i.e., always the 1H‐indazol‐3‐ol tautomer predominates.     

Synthesis and Crystal Structure of 3,3,6,6‐Tetramethylmorpholine‐2,5‐dione,and Its 5‐Monothioxo and 2,5‐Dithioxo Derivatives

The synthesis of 3,3‐dimethylmorpholine‐2,5‐diones 4a was achieved conveniently via the ‘direct amide cyclization’ of the linear precursors of type 3 , which were prepared by coupling of 2,2‐dimethyl‐2H‐azirin‐3‐amines 2 with 2‐hydroxyalkanoic acids 1 . Thionation of 4a with Lawesson's reagent yielded the corresponding 5‐thioxomorpholin‐2‐ones 10 and morpholine‐2,5‐dithiones 11 , respectively, depending on the reaction conditions. The structures of 3aa, 4aa, 10a , and 11a were established by X‐ray crystallography. All attempts to prepare S‐containing morpholine‐2,5‐dione analogs or thiomorpholine‐2,5‐diones by cyclization of corresponding S‐containing precursors were unsuccessful and led to various other products. The structures of some of them have also been established by X‐ray crystallography.     

Synthesis,Characterization, Crystal and Molecular Structure of 1,5‐Dihydro‐2H‐cyclopenta[1,2‐b:5,4‐b′]dipyridin‐2‐imine

The reaction of 1,5‐dihydro‐2H‐cyclopenta[1,2‐b:5,4‐b′]dipyridin‐2‐one ( 3 ) with an alkylamine (butylamine, hexylamine or ethylenediamine) yields, quite unexpectedly and in the absence of catalyst, the novel compound 1,5‐dihydro‐2H‐cyclopenta[1,2‐b:5,4‐b′]dipyridin‐2‐imine ( 4 ) as the sole, analytically pure, solid product, which was fully characterized. The structure of 4 was unequivocally solved by single‐crystal X‐ray‐diffraction analysis. The compound crystallizes in a monoclinic cell (space group P 2₁/c), with two molecules in the asymmetric unit, held together by intermolecular H‐bonds. Compound 4 could be interesting as a bi‐ or even tridentate ligand, and exhibits a strong fluorescence upon excitation at 310 nm. A mechanism, based on the observed C? N bond cleavage, is proposed.     

X‐Ray Structure Analyses of syn/anti‐Conformers of N‐Furfuroyl‐, N‐Benzoyl‐, and N‐Picolinoyl‐Substituted (2R)‐Bornane‐10,2‐sultam Derivatives

The synthesis and the X‐ray structure of the three new N‐(arylcarbonyl)‐substituted derivatives 2a – 2c of (2R)‐bornane‐10,2‐sultam are presented and discussed. Direct comparison of the solid‐state analyses shows that the dipole‐directed SO₂/C?O anti‐/syn‐conformations may be very sensitive to weak electronic/electrostatic repulsions of the heteroatom lone pairs. The optimum interactions are reached when the lone pair of the β‐positioned heteroatom is oriented in the O(3)?C(11)? N(1) plane. Such rare syn‐conformations may be observed with at least up to 1.8 kcal/mol higher energy as compared to their ground states. Additionally, these anti/syn‐conformations are also very sensitive to external influences such as, for example, the crystal‐packing forces.     

2‐Amino‐1,2,3,6‐tetrahydro‐6‐oxocyclopenta[c]fluorene‐2‐carboxylic Acid (FlAib), a Completely Rigidified,Fluoren‐9‐one‐Based α‐Amino Acid

The synthesis, optical resolution, determination of absolute configuration and conformational preference, and spectroscopic characteristics of terminally protected (blocked) derivatives and short peptides of 2‐amino‐1,2,3,6‐tetrahydro‐6‐oxocyclopenta[c]fluorene‐2‐carboxylic acid (FlAib), a novel, rigid, chiral, cyclized C^α,α‐disubstituted glycine are described.     

Reactions of α,β‐Unsaturated Thioamides with Diazo Compounds

Several reactions of the α,β‐unsaturated thioamide 8 with diazo compounds 1a – 1d were investigated. The reactions with CH₂N₂ ( 1a ), diazocyclohexane ( 1b ), and phenyldiazomethane ( 1c ) proceeded via a 1,3‐dipolar cycloaddition of the diazo dipole at the C?C bond to give the corresponding 4,5‐dihydro‐1H‐pyrazole‐3‐carbothioamides 12a – 12c , i.e., the regioisomer which arose from the bond formation between the N‐terminus of the diazo compound and the C(α)‐atom of 8 . In the reaction of 1a with 8 , the initially formed cycloadduct, the 4,5‐dihydro‐3H‐pyrazole‐3‐carbothioamide 11a , was obtained after a short reaction time. In the case of 1c , two tautomers 12c and 12c ′ were formed, which, by derivatization with 2‐chlorobenzoyl chloride 14 , led to the crystalline products 15 and 15 ′. Their structures were established by X‐ray crystallography. From the reaction of 8 and ethyl diazoacetate ( 1d ), the opposite regioisomer 13 was formed. The monosubstituted thioamide 16 reacted with 1a to give the unstable 4,5‐dihydro‐1H‐pyrazole‐3‐carbothioamide 17 .     

Synthesis and Asymmetric Oxidation of (Caranylsulfanyl)‐1H‐imidazoles

For the first time 2‐(cis‐caran‐4‐ylsulfanyl)‐1H‐imidazole, 1‐methyl‐2‐(cis‐caran‐4‐ylsulfanyl)‐1H‐imidazole, and 2‐(cis‐caran‐4‐ylsulfanyl)‐1H‐benzimidazole (carane=3,7,7‐trimethylbicyclo[4.1.0]heptane) were synthesized, and the asymmetric oxidation of these compounds was also carried out. It was shown that oxidation by the Bolm system and the modified system of Sharpless lead to corresponding sulfoxides with de values of 91–100%.     

One‐Pot Diastereoselective Synthesis of Densely Functionalized 2H‐Indeno[2,1‐b]furans. Single‐Crystal X‐Ray Structure of Dimethyl 8,8a‐Dihydro‐8‐oxo‐8a‐(2,2,2‐trichloroethoxy)‐2H‐indeno[2,1‐b]furan‐2,3‐di­carboxylate

Highly reactive 1 : 1 intermediates were produced in the reaction of Ph₃P and dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates). Protonation of these intermediates by alcohols (2,2,2‐trichloroethanol, propargyl alcohol (=prop‐2‐yn‐1‐ol), MeOH, benzyl alcohol, and allyl alcohol (=prop‐2‐en‐1‐ol) led to vinyltriphenylphosphonium salts 4 , which underwent a Michael addition reaction with the conjugate base to produce the corresponding stabilized phosphonium ylides 5 (Scheme). Wittig reaction of the stabilized phosphonium ylides with ninhydrin ( 6 ) led to the corresponding densely functionalized 2H‐indeno[2,1‐b]furans 10 in fairly good yields (Table 1). The structures of the final products were confirmed by IR, ¹H‐ and ¹³C‐NMR spectroscopy, and mass spectrometry. The configuration of dimethyl 8,8a‐dihydro‐8‐oxo‐8a‐(2,2,2‐trichloroethoxy)‐2H‐indeno[2,1‐b]furan‐2,3‐dicarboxylate ( 10a ) was established by a single‐crystal X‐ray structure determination, establishing that the one‐pot multicomponent condensation reaction was completely diastereoselective.     

Synthesis,Interionic Structure,and Reactivity toward CO and p‐Methylstyrene of Palladacyclic Compounds Bearing α‐Diimine Ligands

Palladacyclic compounds [Pd(C₆H₄(C₆H₅C?O)C?N? R)(N? N)] [X] (R = Et, ⁱPr, 2,6‐ⁱPr₂C₆H₃; N? N = bpy = 2,2′‐bipyridine, or 1,4‐(o,o′‐dialkylaryl)‐1,4‐diazabuta‐1,3‐dienes; [X]^? = [BF₄]^? or [PF₆]^?) were synthesized from the dimers [{Pd(C₆H₄(C₆H₅C?O)C?N? R)(μ‐Cl)}₂] and N? N ligands. Their interionic structure in CD₂Cl₂ was determined by means of ¹⁹F,¹H‐HOESY experiments and compared with that in the solid state derived from X‐ray single‐crystal studies. [Pd(C₆H₄(C₆H₅C?O)C?N? R)(N? N)] [X] complexes were found to copolymerize CO and p‐methylstyrene affording syndiotactic or isotactic copolymers when bpy or 1,4‐(o,o′‐dimethylaryl)‐1,4‐diazabuta‐1,3‐dienes were used, respectively. The reactions with CO and p‐methylstyrene of the bpy derivatives were investigated. Two intermediates derived from a single and a double insertion of CO into the Pd? C bonds were isolated and completely characterized in solution.     

A New Germanium Complex Containing Chelating Pyridinecarboxylate Ligands: cis‐Dihydroxybis(pyridine‐2‐carboxylato‐κN1,κO2)germanium Hydrate (1 : 2) (cis‐[Ge(pyca)2(OH)2]⋅2 H2O)

A new germanium complex, cis‐[Ge(pyca)₂(OH)₂]?2 H₂O ( 1 ; pyca=pyridine‐2‐carboxylato), was synthesized by the reaction of [Ge(acac)₂Cl₂] (acac=acetylacetonato=pentane‐2,4‐dionato) with potassium pyridine‐2‐carboxylate (Kpyca) in H₂O/THF. According to the single‐crystal X‐ray diffraction analysis, each Ge‐atom of 1 is coordinated by two pyca ligands and two OH^? groups (Fig. 1). These molecules are bonded to each other via a system of H‐bonds resulting in a sheet‐like structure (Fig. 2). The complex is decomposed during heating with stepwise mass loss and formation of GeO₂ as final product (Fig. 3).     

Preparation and Structures of 2‐Substituted 5‐Benzyl‐3‐methylimidazolidin‐4‐one‐Derived Iminium Salts,Reactive Intermediates in Organocatalytic Transformations Involving α,β‐Unsaturated Aldehydes

Preparations of the title compounds, 5 – 7 (Scheme 1 and Table 1), of their ammonium salts, 9 – 11 (Scheme 2 and Table 2), and of the corresponding cinnamaldehyde‐derived iminium salts 12 – 14 (Scheme 3 and Table 3) are reported. The X‐ray crystal structures of 15 cinnamyliminium PF₆ salts have been determined (Table 4). Selected ¹H‐NMR data (Table 5) of the ammonium and iminium salts are discussed, and structures in solution are compared with those in the solid state.     

The Biomimetic Synthesis and Final Structure Determination of (+)‐ and (−)‐Centrolobine,Naturally Occurring Diarylheptanoid 2,6‐cis‐Disubstituted Tetrahydro‐2H‐pyrans

The enantiomerically pure title compounds were prepared by oxidative cyclization of their optically active diarylheptanoid precursors. The approach is considered as a biomimetic phenol oxidation via an intermediate quinone methide. The absolute configuration of the precursors is retained, and the transition state adopts the sterically most favorable diequatorial arrangement of the 2,6‐substituents to afford the cis‐configured natural products. The outcome unambiguously establishes the absolute configurations and the correlation with the chiroptical data. In addition, a problem of regioisomerism that had not been discussed before was solved, and the original assignment of the position of the MeO group in the natural centrolobines could be confirmed. As such the results are the experimental evidence for the corrections of long‐term inconsistencies we had postulated in an earlier review article.