Geminal Substituents Research Articles

Understanding the Structure-Polymerization Thermodynamics Relationships of Fused-Ring Cyclooctenes for Developing Chemically Recyclable Polymers.

Polymers that can be chemically recycled to their constituent monomers offer a promising solution to address the challenges in plastics sustainability through a circular use of materials. The design and development of monomers for next-generation chemically recyclable polymers require an understanding of the relationships between the structure of the monomers/polymers and the thermodynamics of polymerization/depolymerization. Here we investigate the structure-polymerization thermodynamics relationships of a series of cyclooctene monomers that contain an additional ring fused at the 5,6-positions, including trans-cyclobutane, trans-cyclopentane, and trans-five-membered cyclic acetals. The four- and five-membered rings trans-fused to cyclooctene reduce the ring strain energies of the monomer, and the enthalpy changes of polymerizations are found to be in the range of -2.1 to -3.3 kcal mol-1. Despite the narrow range of enthalpy changes, the ceiling temperatures at 1.0 M span from 330 to 680 °C, due to the low entropy changes, ranging from -2.7 to -5.0 cal mol-1 K-1. Importantly, geminal substituents on the trans-five-membered cyclic acetal fused cyclooctenes are found to reduce the ceiling temperature by ∼300 °C, although they are not directly attached to the cyclooctene. The remote gem-disubstituent effect demonstrated here can be leveraged to promote depolymerization of the corresponding polymers and to tune their thermomechanical properties.

Group 14 Central Atoms and Halogen Bonding in Different Dielectric Environments: How Germanium Outperforms Silicon.

The nature of halogen bonding under different dielectric conditions remains underexplored, especially for inorganic systems. The structural and energetic properties of model halogen bonded complexes (R3 M-I-NH3 for R=H and F, and M=C, Si, and Ge) are examined computationally for relative permittivities between 1 and 109 using an implicit solvent model. We confirm and assess the exceptionally high maximum potentials at the sigma hole on I (Vs,max ) in F3 Ge-I relative to cases where M=C or Si. In particular, Ge far outperforms Si in mediating inductive effects. Linear relationships, typically with R2 >0.97, are identified between Vs,max , the full point charge on I in R3 M-I, and the interaction energy, and optimized I-N distance in the complexes. An anomalous trend is identified in which, for each M, F3 M-I-NH3 becomes less stable as the optimized I-N distance gets shorter in different dielectric environments; it is explained using the F-I-NH3 complex as a reference.

Synthesis of Forms of a Chiral Ruthenium Complex Containing a Ru-Colefin(sp2) Bond and Their Application to Catalytic Asymmetric Cyclopropanation Reactions.

Organometallic complexes [Ru-Colefin(sp2)-Ru(II)-Pheox 2a-2d] containing a Ru-Colefin(sp2) bond have been prepared from unsaturated chiral oxazoline derivatives and evaluated for asymmetric cyclopropanation reactions. The corresponding optically active cyclopropanes were obtained with high yields and high stereoselectivities (≥99/<1 trans/cis, 99% trans ee). The enantioselectivities were found to be affected by the geminal substituent on the Ru-C(sp2) bond. In particular, Ru(II)-Prox catalyst 2c, in which there was no geminal substituent on the metal, was shown to have the highest enantioselectivities.

Copper-Catalyzed Enantio- and Diastereoselective Addition of Silicon Nucleophiles to 3,3-Disubstituted Cyclopropenes.

A highly stereocontrolled syn‐addition of silicon nucleophiles across cyclopropenes with two different geminal substituents at C3 is reported. Diastereomeric ratios are excellent throughout (d.r.≥98:2) and enantiomeric excesses usually higher than 90 %, even reaching 99 %. This copper‐catalyzed C−Si bond formation closes the gap of the direct synthesis of α‐chiral cyclopropylsilanes.

Conformational rivalry of geminal substituents in silacyclohexane derivatives: 1-Phenyl vs. 1-OR, R=H or Me

Molecular structure and conformational equilibria of 1-methoxy- 1 and 1-hydroxy-1-phenylsilacyclohexanes 2 were studied by quantum chemical (QC) calculations and combined gas electron diffraction/mass spectrometry (GED/MS). Both molecules may exist in 5 or 6 forms, differing from each other by the substituents' position: (i) axial or equatorial and (ii) rotational orientation relative to the six-membered ring frame. The contribution of axial forms of both compounds varies from 35 to 60% depending on the theoretical method applied. From the GED data, the summarized molar fractions of the conformers were found to be Phax:Pheq = 70(15):30(20) and 50(20):50(20)% which corresponds to ΔG = Gax–Geq = −0.55(46) and 0.00(56) kcal/mol, for compound 1 and 2, respectively. The concentration of the Phax forms of 1-phenyl-1-(X)-silacyclohexanes (X = H, HO, Me, MeO and Me2N) increases with the size of the second substituent at the silicon atom: 38(10)<50(20)<58(15)<70(15) <80(15)%.

Asymmetric [3 + 2] Cycloaddition of Vinylcyclopropanes and α,β-Unsaturated Aldehydes by Synergistic Palladium and Organocatalysis.

The stereoselective [3 + 2] cycloaddition between vinylcyclopropanes and α,β-unsaturated aldehydes promoted by combined palladium and organocatalysis is disclosed. The unique synergistic catalytic system allows for the stereoselective formation of highly substituted cyclopentanes with up to four stereocenters in high yields and selectivities. Vinylcyclopropanes with two different geminal substituents facilitate the formation of cyclopentanes containing a quaternary stereocenter. Furthermore, the developed reaction performs well on gram scale, and a number of transformations are demonstrated.

Design, Synthesis, and Applications of Potential Substitutes of t-Bu-Phosphinooxazoline in Pd-Catalyzed Asymmetric Transformations and Their Use for the Improvement of the Enantioselectivity in the Pd-Catalyzed Allylation Reaction of Fluorinated Allyl Enol Carbonates

The design, synthesis, and applications of potential substitutes of t-Bu-PHOX in asymmetric catalysis is reported. The design relies on the incorporation of geminal substituents at C5 in combination with a substituent at C4 other than t-butyl (i-Pr, i-Bu, or s-Bu). Most of these new members of the PHOX ligand family behave similarly in terms of stereoinduction to t-Bu-PHOX in three palladium-catalyzed asymmetric transformations. Electronically modified ligands were also prepared and used to improve the enantioselectivity in the Pd-catalyzed allylation reaction of fluorinated allyl enol carbonates.

4-(4,6-Di[2,2,2-trifluoroethoxy]-1,3,5-triazin-2-yl)-4-methylomorpholinium Tetrafluoroborate. Triazine-Based Coupling Reagents Designed for Coupling Sterically Hindered Substrates

4-(4,6-Di[2,2,2-trifluoroethoxy]-1,3,5-triazin-2-yl)-4-methylomorpholinium tetrafluoroborate (DFET/NMM/BF(4)) was prepared and used as a reagent for coupling sterically hindered substrates. The formation of the appropriate triazine "superactive" ester in a reaction of DFET/NMM/BF(4) with carboxylic acids was confirmed. The efficiency of the reagent has been studied in the synthesis of Leu-enkephaline pentapeptide carried out on a Fmoc-RinkAmide-AM-PS resin, by systematically modifying the -Gly-Gly- fragment for N-methyl or α,α-disubstituted residues and compared with the efficiency of classic aminium salt 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) under a variety of reaction conditions. In syntheses of Aib-Aib (Aib: α-aminoisobutyric acid), MeVal-MeVal, and MeLeu-MeLeu, the considerably superior performance of enkephaline analogues was obtained for DFET/NMM/BF(4) relative to TBTU, regardless of reaction conditions. Analysis of the couplings involving triazine reagent suggests that factors controlling efficiency of coupling sterically hindered substrates are the structure of the leaving group permitting formation of the cyclic intermediate or cyclic transition state and the absence of strongly solvating solvents. It has to be considered as highly probable that the absence of strongly solvating milieu favors cyclic intermediates or the cyclic transition state. Arrangement of both components into the cyclic intermediate or cyclic transition state by accumulation of the geminal (vicinal) substituents effect (known as the Thorpe-Ingold effect) would compensate retardation of the coupling process caused by steric hindrance.

ChemInform Abstract: Conformational Analysis on Cyclohexane, Oxane, and Thiane Derivatives Bearing Two Geminal Electron-Withdrawing Groups and Acetoxy Substituents at the β and β′ Carbons.

Abstract A qualitative conformational analysis on cyclohexane, oxane, and thiane structures bearing two geminal electron-withdrawing groups and having two acetoxy substituents at the β and β′ positions has been performed. The predominant conformation in thiane structures is determined by a preponderant hockey-stick effect. In the other structures, the predominant conformation is determinated by the competition between stabilizing gauche and destabilizing steric effects depending on the R1 and R2 bulks. Molecular mechanics procedure reproduces the conformational behaviour in compounds 25–32. Crystals of 29 are triclinic, P-1, a= 9.607(6), b= 13.437(8), c= 14.838(8)A , α= 106.50(7) β= 98.61(6), β= 91.17°, V= 1836(2) A3, Z=4, Dx= 1.246 Mg·m−3, λ (Mo Kα) = 0.71069 A, μ= 0.094 mm−1, F(000)= 736, T= 293 °K, R= 0.046 and wR= 0.063, S= 0.88, for 2277 unique observed reflections with F2o 8σ(F2o). The bond lengths and angles are normal and do not reflect delocalization.

ChemInform Abstract: Geminal Substituent Effects. Part 4. The Dependence of the Inverse Anomeric Effect of Geminal Cyano Groups on the Structure.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Sulfoxide-Induced Stereoselection in [1,5]-Sigmatropic Hydrogen Shifts of Vinylallenes. A Computational Study

The sulfoxide-induced preference for a migrating trajectory in the vinylallene [1,5]-H sigmatropic shift (resulting in stereodefined trienes in the conceptual equivalent of torquoselectivity in electrocyclizations), originally reported by Okamura, has been computationally studied at the B3LYP/6-311++G(3df,2p)//B3LYP/6-31++G(d,p) level. The face selectivity this group induces in the [1,5]-H shift is enhanced by bulky geminal substituents and is not reproduced by any of the other (more than 20) substituents tested. Analysis of transition-state geometries or charges and evaluation of steric effects did not show any correlation with the preferences. The origin of this selectivity is thought to lie in a secondary orbital interaction (SOI) involving the termini of the pericyclic array and the sulfinyl group which is only observed for this substituent. This secondary orbital interaction, arising from the favorable energies of the orbitals involved, is enhanced in the transition structure due to a better orbital overlap (piC2-C3-->sigma*C1-S), which correlates with a piC2-C3-->sigma*C6-H SOI, which is more important in the transition structure, that weakens the C-H bond, thus lowering the energy of the corresponding transition structure.

Vinyldimethylphenylsilanes as Safety Catch Silanols in Fluoride‐Free Palladium‐Catalyzed Cross‐Coupling Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Catalytic [4+1] Cycloaddition of α,β-Unsaturated Carbonyl Compounds with Isocyanides

The GaCl(3)-catalyzed [4+1] cycloaddition reactions of alpha,beta-unsaturated ketones with isocyanides leading to lactone derivatives are described. While some other Lewis acids also show catalytic activity, GaCl(3) was the most efficient catalyst. The reaction is significantly affected by the structure of both the isocyanides and the alpha,beta-unsaturated ketones. Aromatic isocyanides, especially sterically demanding ones and those bearing an electron-withdrawing group, can be used, but aliphatic isocyanides cannot. The bulkiness of substituents at the beta-position of acyclic alpha,beta-unsaturated ketones is an important factor for the reaction to proceed efficiently. Generally, the more the bulky substituent, the higher is the yield. The reaction of alpha,beta-unsaturated ketones bearing geminal substituents at the beta-position gave the corresponding products in high yields. In monosubstituted derivatives, the yields are relatively low. However, substrates having a bulky substituent, such as a tert-Bu group, at the beta-position give high yields. Bulkiness is also required in cyclic alpha,beta-unsaturated ketones, but the effect is small. In alkyl vinyl ketones, the reactivity decreased with the steric bulk of the alkyl group. In aryl vinyl ketones, the presence of an electron-donating group on the aromatic ring decreases the reactivity. The success of the catalysis can be attributed to the low affinity of GaCl(3) toward heteroatoms, compared with usual Lewis acids.

Vinyldimethylphenylsilanes as Safety Catch Silanols in Fluoride-Free Palladium-Catalyzed Cross-Coupling Reactions

A series of five structurally diverse vinyldimethylphenylsilanes have been shown to undergo a fluoride-free one-pot palladium-catalyzed cross-coupling reaction with phenyl iodide to give ipso coupled products in 62-86% yield. The limitations of this present protocol lie in the activation of Si-Ph vs protodesilylation by KOTMS/18-C-6, which seems sensitive to the sterics of cis substituents, but not geminal substituents.

Synthesis and Conformational Studies of Methylated, Highly Branched Fluoroolefins: Gear‐Meshed Conformational Isomers

AbstractMethylated, highly branched fluoroolefins were prepared by treatment of hexafluoropropene trimers with CH3Li and CH3MgBr. Their structures, which included some rotational isomers, were determined by NMR and GC‐MS and were further confirmed by B3LYP‐GIAO calculation of NMR shieldings. Of the seven methylated fluoroolefins isolated in pure states, three were shown to be mixtures of pairs of conformational isomers. The methylated fluoroolefins containing two bulky geminal substituents such as (CF3)2CF and (CF3)2CCH3 showed gear‐meshed conformations in which the two bulky substituents were conformationally locked. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)

Study of Unusually High Rotational Barriers about SN Bonds in Nonafluorobutane‐1‐sulfonamides: The Electronic Nature of the Torsional Effect

AbstractSlow rotation about the SN bond in N,N‐disubstituted nonafluorobutane‐1‐sulfonamides 1 can easily be detected by NMR measurements at room temperature. This effect causes magnetic nonequivalence of otherwise identical geminal substituents in symmetrical staggered ground‐state conformation A. The torsional barriers determined (62–71 kJ⋅mol−1) proved to be the highest ever observed for sulfonamide moieties. They are comparable to the values routinely measured for carboxylic acid amides or carbamates. The restricted rotation is interpreted as result (nNdS)‐π and of nNσ interactions, which develop substantial S,N double‐bond character in sulfonamides 1. The S,N binding interaction is increased by the highly electron‐withdrawing effect of the perfluorobutyl group. The anticipated symmetry of the ground‐state conformation A and the considerable shortening of the SN bond (1.59 Å) compared to the mean value in sulfonamides (1.63 Å) are confirmed by single‐crystal X‐ray study of N,N‐dibenzylnonafluorobutane‐1‐sulfonamide (1c).

Crowded piperidines with intramolecularly hydrogen-bonded nitrogen: synthesis and conformation study.

2,2,6,6-Tetramethyl substituted piperidines with a beta-branched N-alkyl substituent were synthesized by the photoreaction of N-Me precursors with ketones. The main conformation features of these sterically-hindered amines (established by NMR and IR spectroscopy) are a ring in the chair form, an eclipsed conformation for the N-substituent and an intramolecular OH...N bond. High barriers for the geminal substituent topomerization were measured for these piperidines at different temperatures by means of line-shape analysis of the temperature-dependent 13C and 1H NMR spectra. An MM3-derived conformation scheme indicated that, for one of the studied analogues, the rotation of the N-substituent determines a slow topomerization rate. A new mechanism of nitrogen inversion--a concerted hydrogen-bond dissociation/nitrogen inversion process--is considered for hydrogen-bonded amines.

A novel thermosensitive polymer, poly(methyl 2-propionamidoacrylate), with geminal substituents

A novel thermosensitive polymer, poly(methyl 2-propionamidoacrylate) (PMPA), was prepared and the phase transition behavior in an aqueous solution was studied. PMPA have geminal substituents of propionamide and methoxy carbonyl in each monomer unit. It was found that PMPA shows the lower critical solution temperature (LCST) at 50.6°C sharply. The LCST of PMPA was almost independent of the polymer concentration above 40g/l, while, below 40g/l, it decreased with the increasing polymer concentration. The effect of salt addition (NaCl, NaBr, and Na2SO4) on the LCST was also studied. The LCST of PMPA linearly decreased with the increasing concentration of each salt. The salting-out effect of these salts was in line with the Hofmeister series: Na2SO4>NaCl>NaBr.

CD Spectra in Methanol ofβ-Oligopeptides Consisting ofβ-Amino Acids with Functionalized Side Chains, with Alternating Configuration, and with Geminal Backbone Substituents - Fingerprints of New Secondary Structures?

β-Hexa-, β-hepta-, and β-nonapeptides, 1 – 6, which carry functionalized side chains (CO2R, CO, (CH2)4NH, CH2−CH=CH2) consisting of β3-amino-acid residues of alternating configuration, or which carry geminal substituents in the 2- or 3-positions of all residues, have been synthesized (Schemes 1 – 3), and their CD spectra in MeOH are reported (Figs. 2 – 6). Strong Cotton effects (Θ>105) are indicative of the presence of chiral secondary structures. It is suggested by simple modelling (Fig. 1) that the new β-peptides should not be able to fold to the familiar 314-helical structures. Still, three of them (3, 4, and 5) give rise to CD spectra matching those of β-peptides that are known to be present as (M)- or (P)-314-helices in MeOH solution. While possible folding motifs (Figs. 3,b, and 7) of the new β-peptides have been identified in crystal structures, an interpretation of the CD spectra has to be postponed until NMR solution structures become available. A list of all β-peptides giving rise to CD spectra with a minimum near 215 nm is included (Table).

Mass spectral fragmentation pathways in cyclic difluoramino and nitro compounds

The recently synthesized compounds 4, 4-bis(difluoramino)-1-nitropiperidine (I), 1,4,4-trinitropiperidine (II), 1,1,4,4-tetranitrocyclohexane (III), 1,1,4, 4-tetrakis(difluoramino)cyclohexane (IV) and 3,3,7, 7-tetrakis(difluora-mino)octahydro-1,5-dinitro-1,5-diazocine (HNFX, V) are being considered as potential energetic materials. The mass spectra of these compounds were studied using electron ionization (EI) mass spectrometry. A collision-induced dissociation (CID) study of the major EI peaks was carried out using a Finnigan TSQ 700 tandem mass spectrometer. The mass fragmentation pathways are constructed and discussed. The decomposition of HNFX (V), under EI, appeared to parallel the thermal decomposition of nitramines where N-NO(2) cleavage is often the first step. However, the two nitramines with a six-membered ring structure (I and II) underwent initial loss of a geminal substituent; loss of a nitramine nitro group was the secondary step. The two cyclohexane structures (III and IV) showed similar initial fragmentation pathways, featuring successive losses of nitro or difluoramino groups. Copyright 2000 John Wiley & Sons, Ltd.