Conformational analysis and stereochemical dependences of 31P–1H spin–spin coupling constants of bis(2‐phenethyl)vinylphosphine and related phosphine chalcogenides

Theoretical energy‐based conformational analysis of bis(2‐phenethyl)vinylphosphine and related phosphine oxide, sulfide and selenide synthesized from available secondary phosphine chalcogenides and vinyl sulfoxides is performed at the MP2/6‐311G** level to study stereochemical behavior of their ³¹P–¹H spin–spin coupling constants measured experimentally and calculated at different levels of theory. All four title compounds are shown to exist in the equilibrium mixture of two conformers: major planar s‐cis and minor orthogonal ones, while ³¹P–¹ H spin–spin coupling constants under study are found to demonstrate marked stereochemical dependences with respect to the geometry of the coupling pathways, and to the internal rotation of the vinyl group around the P(X)‐C bonds (X = LP, O, S and Se), opening a new guide in the conformational studies of unsaturated phosphines and phosphine chalcogenides. Copyright © 2009 John Wiley & Sons, Ltd.     

Cyclization reactions of 4-(3′-butenyl)azetidin-2-one a route to the carbopenam ring system

Cyclization of 4-(3′-butenyl)azetidin-2-one, $\text{2}$ initiated by electrophilic reagents such as I₂, Hg(OAc)₂ results in the formation of bicyclic β-lactams having the carbopenam ring skeleton. Reaction of $\text{2}$ with Br₂ results in simple addition of Br₂ to the double bond, while PhSBr gives a mixture of cyclization and addition products.     

Conformational Analysis of Biphenyl Derivatives. I. A Novel Steric Constant from the Internal Rotation Rate of 2,2′‐Bis‐(N‐Substituted Carbamoylmethyl)Biphenyl by Means of Dynamic NMR

A novel scale of steric substituent constant E_s^D is defined from the correlation of the logarithms of the internal rotation rate (k_r) at 393 K with Hancock (E_s^c) steric constant by means of dynamic NMR. In the inhibition of Pseudomona species lipase by 2,2′‐bis‐(N‐substituted carbamoylmethyl)biphenyls (1‐8), the logarithms of bimolecular rate constants are multiply correlated with both the Taft substituent constant σ* and E_s^D.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 10. Synthesis and structure determination of naphtho[1′,2′:4,5]thieno[3,2-a]-4,7-phenanthroline

Naphtho[1′,2′:4,5]thieno[3,2-a]-4,7-phenanthroline, a novel hexacyclic ring system has been synthesized in four steps. The ¹H and ¹³C nmr assignments have been made using two-dimensional nmr techniques. The tertiary helical structure was determined by X-ray crystallographic analysis.     

Studies in spiroheterocycles. Part XIII. Synthesis of a novel spiro system: Spiro[9H-acridine-9,3′-[3h]indol]-2′(1′H)-one and related compounds from new fluorinated spiro[3H-indole-3,9′-[9H]xanthen]-2(1H)-ones

A new spiroheterocyclic system spiro[9H-acridine-9,3′-[3H]indol]-2′(1′H)-one and related compounds have been prepared by the reaction of spiro[3H-indole-3,9′-[9H]xanthen]-2(1H)-ones with aromatic amine or ammonium acetate. The latter were prepared by heating fluorinated indole-2,3-diones with m-/p-cresols or α-naphthol in the presence of sulphuric acid at 230-240°. The synthesized compounds have been characterized on the basis of their elemental analyses, ir, nmr (1_H, 13_C, 19_F) and mass spectral data.     

Nucleic-Acid Analogues with Constraint Conformational Flexibility in the Sugar-Phosphate Backbone (‘Bicyclo-DNA’). Part 1. Preparation of (3S,5′R)-2′-Deoxy-3′,5′-ethano-αβ-D-ribonucleosides (‘Bicyclonucleosides’)

We describe the synthesis of 2′-deoxy-3′,5′-ethano-D -ribonucleosides 1 – 8 (= (5′,8′-dihydroxy-2′-oxabicyclo-[3.3.0]oct-3′-yl)purines or -pyrimidines) of the nucleobases adenine, thymine, cytosine, and guanine. They differ from natural 2′-deoxyribonucleosides only by an additional ethylene bridge between the centers C(3′) and C(5′). The configuration at these centers (3S,5′R) was chosen as to match the geometry of a repeating nucleoside unit in duplex DNA as close as possible. These nucleosides were designed to confer, as constituents of an oligonucleotide chain, a higher degree of preorganization of a single strand for duplex formation with respect to natural DNA, thus leading to an entropic advantage for the pairing process. The synthesis of these ‘bicyclonucleosides’ was achieved by construction of an enantiomerically pure carbohydrate precursor 18 / 19 (Schemes 1), which was then converted to the corresponding nucleosides by known methods in nucleoside synthesis (Schemes 2 and 3). In all cases, both anomeric forms of the nucleosides were obtained in pure crystalline form, the relative configuration of which was established by ¹H-NMR-NOE spectroscopy. A conformational analysis of the nucleosides with β-configuration at the anomeric center by means of X-ray and ¹H-NMR (including NOE) spectroscopy show the furanose part of the molecules to adopt uniformly a 1′exo-conformation with the base substituents preferentially in the anti-range in the pyrimidine nucleosides (anti/syn ca. 2:1) distribution in the purine nucleosides (in solution).     

Nucleotides. Part XLII. The 2-dansylethoxycarbonyl (= 2-{[5-(dimethylamino)naphthalen-1-yl]sulfonyl}ethoxycarbonyl; dnseoc) group for protection of the 5′-hydroxy function in oligoribonucleotide synthesis

The 2-dansylethoxycarbonyl (Dnseoc) group was employed for protection of the 5′-hydroxy function in oligoribonucleotide synthesis by the phosphoramidite approach using the acid-labile tetrahydro-4-methoxy-2H-pyran-4-yl (Thmp) group for 2′-protection. The syntheses of monomeric building blocks, both phosphoramidites and nucleoside-functionalized supports, are described for the four common nucleosides adenosine, guanosine, cytidine, and uridine, and for the two modified minor nucleosides ribothymidine (= ribosylthymine) and pseudouridine.     

Nucleotides. Part XLIII. Solid-phase synthesis of oligoribonucleotides using the 2-dansylethoxycarbonyl (  2-{[5-(dimethylamino)naphthalen-1-yl]sulfonyl}ethoxycarbonyl; dnseoc) group for 5′-hydroxy protection

A new efficient method for solid-phase synthesis of oligoribonucleotides via the phosphoramidite approach is described. The combination of the base-labile 2-dansylethoxycarbonyl (Dnseoc) group for 5′-OH protection with the acid-labile tetrahydro-4-methoxy-2H-pyran-4-yl (Thmp) group as 2′-OH blocking group is orthogonal regarding cleavage reactions and fulfills the requirements of an automated synthesis in an excellent manner if the phosphoramidite function carries the N,N-diethyl-O-[2-(4-nitrophenyl)ethyl] substitution.     

Nucleotides. Part XLI. The 2-dansylethoxycarbonyl (  2-{[5-(dimethylamino)naphthalen-1-yl]sulfonyl}ethoxycarbonyl; dnseoc) group for protection of the 5′-hydroxy function in oligodeoxyribonucleotide synthesis

Use of the 2-dansylethoxycarbonyl ( ? 2-{[5-(dimethylamino)naphthalen-1-yl]sulfonyl}ethoxycarbonyl; Dnseoc) group as an intermediate 5′-OH protecting group in oligodeoxyribonucleotide synthesis using the automated phosphoramidite approach is described in a model study to an alternative strategy in RNA synthesis.     

The chemistry of 2H-1,3-benzoxazine-2,4-(1H)dione (isatoic anhydride). 8. A one step synthesis of the quinindoline ring system and related compounds

The reaction between N-substituted isatoic anhydrides and the carbanion generated from 3-methylthio-oxindole to produce the quinindoline ring skeleton is discussed. Analogous reactions of azaisatoic anhydride 6 and tricyclic anhydride 8 produces the 4-aza analog 7 and pentacycle 9 . Some spectral data is also described.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 4 . Benzo[f]thieno[2′,3′:4,5]thieno[2,3-c]quinoline and Benzo[h]thieno[2′,3′:4,5]thieno[2,3-c]quinoline and the total assignment of their 1H- and 13C-NMR spectra

The synthesis of two novel polycyclic heterocyclic ring systems via photocyclization are reported. These are benzo[f]thieno[2′,3′:4,5]thieno[2,3-c]quinoline and benzo[A]thieno-[2′,3′:4,5]thieno[2,3-c]quinoline. The total assignment of their ¹H- and ¹³C-nmr spectra was determined by utilizing two-dimensional nmr spectroscopic methods.     

Mixed-ligand complex formation in the copper(I)-2,9-dimethyl-1,10-phenanthroline-3,3′-bonded biquinoline system according to <Superscript>1</Superscript>H NMR data

The reaction of the copper(I) 2,9-dimethyl-1,10-phenanthroline (neocuproine, DMP) complex with 2,3,8,9-dibenzo-4,7-dimethyl-5,6-dihydro-1,10-phenanthroline (cuprotest, DMQ) in a CD₃OD solution has been studied by ¹H NMR spectroscopy. The substitution of DMQ for the DMP liqand in the inner coordination sphere of the Cu⁺ complex has been observed. A model of the process including the formation of a mixed-ligand complex, presumably of bridged structure, is proposed to describe the observed experimental dependences of integrated intensities of the NMR signals in the spectrum on the concentrations of the components of the solution.     

Conformations of the ten-membered ring in 5,10-secosteroids I. X-ray and NMR. Analysis of (E)-3 β-hydroxy-5,10-seco-1(10)-cholesten-5-one esters

X-ray structure determination of the p-bromobenzoate 2b of one of the (E/Z)-isomeric 3β-hydroxy-5,10-seco-1(10)-cholesten-5-ones confirmed the (E)-configuration proposed previously and showed the cyclodecenone ring to adopt an extended crown conformation of type A ₁ (Fig. 9). Analysis of the ¹H- and ¹³C-NMR. spectra of acetate 2a revealed that in solution the ten-membered ring of this steroid exists in at least two distinct forms, the predominant (about 85%) corresponding to the solid-state conformation of 2b (= A ₁), and the minor most likely to B ₂ (Fig. 9). From NMR. data the energy difference between the two species and the relevant activation energy were estimated. A number of conformational force field calculations using a simplified partial structural model was performed; but the computed energy differences between the various possible conformations do not reproduce the effective situation, neither in solution nor in the crystal lattice, indicating that additional effects such as the transannular interaction of the double bond with the carbonyl group may strongly influence the thermodynamic stability of the system. The conformations deduced were used to rationalize the stereochemical course of different chemical reactions of 2a .     

Synthesis, complete NMR assignments, and NOE versus GIAO data assisted ab initio modelling the overall conformations of amide 3,4′-diquinolinyl sulfides in solution. Another approach to analysis of flexible systems

Two isomeric amide sulfides 3 and 4 were prepared by the treatment of 6-substituted thioquinanthrene (2) with sodium methoxide and methyl iodide. Product structures were determined by ¹H and ¹³C NMR spectroscopy in solution, including 2D experiments HSQC and HMBC at 11.75 T. The time-averaged conformations were elucidated, based on best fitting the measured data δ_C and δ_H to those computed by the ab initio GIAO NMR method at the HF/6-31G^* level. All used input molecular models had been pre-selected before in the light of NOE experimental data. Excellent two-nuclear linear correlations δ_C,H^exp vs. δ_C,H^calc were achieved (R>0.999). Spatial orientations of the ring substituents [SMe and, especially, of C(O)NMe₂] in both isomers were considered to rationalise the NMR spectra of these and other related amide systems. A protocol for the three-step conformational analysis is described in detail.