Evaluating cis‐2,6‐Dimethylpiperidide (cis‐DMP) as a Base Component in Lithium‐Mediated Zincation Chemistry

Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6‐tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non‐TMP based mixed‐metal bases and, as cis‐2,6‐dimethylpiperidide (cis‐DMP) was chosen as the alternative amide, developing cis‐DMP zincate chemistry which has received meagre attention compared to that of its methyl‐rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis‐DMP)Et₂] (TMEDA=N,N,N′,N′‐tetramethylethylenediamine) has been synthesised by co‐complexation of Li(cis‐DMP), Et₂Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X‐ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N‐diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis‐DMP)Et₂] has been probed and contrasted with that of the known but previously uninvestigated di‐tert‐butylzincate, [(TMEDA)LiZn(cis‐DMP)tBu₂]. The former was found to be the superior base (for example, producing the ortho‐deuteriated product in respective yields of 78 % and 48 % following D₂O quenching of zincated benzamide intermediates). An 88 % yield of 2‐iodo‐N,N‐diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3‐hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et₂Zn and TMEDA system. Under certain conditions, the cis‐DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di‐tert‐butylzincate and crystallographically characterised, namely the pre‐metallation complex [{(iPr)₂N(Ph)C?O}LiZn(cis‐DMP)tBu₂] and the post‐metallation complex [(TMEDA)Li(cis‐DMP){2‐[1‐C(=O)N(iPr)₂]C₆H₄}Zn(tBu)], shed valuable light on the structures and mechanisms involved in these alkali‐metal‐mediated zincation reactions. Aspects of these reactions are also modelled by DFT calculations.     

cis‐Dioxocyclam

Molecules of 1,4,8,11‐tetra­aza­cyclo­tetra­decane‐5,7‐dione, or cis‐dioxocyclam, C₁₀H₂₀N₄O₂, lie across mirror planes in space group Cmca; the crystal structure reveals interleaved columns of cis‐dioxocyclam mol­ecules along the 2₁ screw axis parallel to the crystallographic b axis. The columns are interconnected in a chain‐like arrangement by an amido hydrogen‐bonding network (N?O = 2.816 Å) and an amino hydrogen‐bonding network (N?N = 3.193 Å). The intracolumn spacing is 9.02 Å.     

Efficient Separation of cis‐ and trans‐1,2‐Dichloroethene Isomers by Adaptive Biphen[3]arene Crystals

Reported here is the highly efficient separation of industrially important cis‐ and trans‐1,2‐dichloroethene (cis‐DCE and trans‐DCE) isomers by activated crystalline 2,2′,4,4′‐tetramethoxyl biphen[3]arene (MeBP3) materials, MeBP3α. MeBP3 can be synthesized in excellent yield (99 %), and a cyclic pentamer is also obtained when using 1,2‐dichloroethane as the solvent. The structure of MeBP3 in the CH₃CN@MeBP3 crystal displays a triangle‐shape topology, forming 1D channels through window‐to‐window packing. Desolvated crystalline MeBP3 materials, MeBP3α, preferentially adsorb cis‐DCE vapors over its trans isomer. MeBP3α is able to separate cis‐DCE from a 50:50 (v/v) cis/trans‐isomer mixture, yielding cis‐DCE with a purity of 96.4 % in a single adsorption cycle. Single‐crystal structures and powder X‐ray diffraction patterns indicate that the uptake of cis‐DCE triggers a solid‐state structural transformation of MeBP3, suggesting the adaptivity of MeBP3α materials during the sorption process. Moreover, the separation can be performed over multiple cycles without loss of separation selectivity and capacity.     

cis‐Verbenol

cis‐Verbenol (alternative name: 4,6,6‐tri­methyl­bi­cyclo­[3.1.1]­hept‐3‐en‐2‐ol), C₁₀H₁₆O, forms an orthorhombic P2₁2₁2₁ crystal that contains three mol­ecules per asymmetric unit. These three mol­ecules form hydrogen‐bonded helices parallel to the shortest axis of the lattice. The O?O distances associated with the hydrogen bonds are 2.760 (3), 2.760 (3) and 2.766 (3) Å.     

Enantioselective Synthesis of Arene cis‐Dihydrodiols from 2‐Pyrones

An enantioselective chemical synthesis of arene cis‐dihydrodiols has been realized from 2‐pyrones through sequential ytterbium‐catalyzed asymmetric inverse‐electron‐demand Diels–Alder (IEDDA) reaction of 2‐pyrones and retro‐Diels–Alder extrusion of CO₂. By using this strategy, a series of substituted arene cis‐dihydrodiols can be obtained efficiently with high enantioselectivity (>99 % ee in many cases). Based on this strategy, efficient and concise asymmetric total syntheses of (+)‐MK7607 and 1‐epi‐(+)‐MK7607 were accomplished.     

Iron‐Catalyzed Highly Enantioselective cis‐Dihydroxylation of Trisubstituted Alkenes with Aqueous H2O2

Reliable methods for enantioselective cis‐dihydroxylation of trisubstituted alkenes are scarce. The iron(II) complex cis‐α‐[Fe^II(2‐Me₂‐BQPN)(OTf)₂], which bears a tetradentate N₄ ligand (Me₂‐BQPN=(R,R)‐N,N′‐dimethyl‐N,N′‐bis(2‐methylquinolin‐8‐yl)‐1,2‐diphenylethane‐1,2‐diamine), was prepared and characterized. With this complex as the catalyst, a broad range of trisubstituted electron‐deficient alkenes were efficiently oxidized to chiral cis‐diols in yields of up to 98 % and up to 99.9 % ee when using hydrogen peroxide (H₂O₂) as oxidant under mild conditions. Experimental studies (including ¹⁸O‐labeling, ESI‐MS, NMR, EPR, and UV/Vis analyses) and DFT calculations were performed to gain mechanistic insight, which suggested possible involvement of a chiral cis‐Fe^V(O)₂ reaction intermediate as an active oxidant. This cis‐[Fe^II(chiral N₄ ligand)]²⁺/H₂O₂ method could be a viable green alternative/complement to the existing OsO₄‐based methods for asymmetric alkene dihydroxylation reactions.     

Water‐Promoted Kinetic Separation of trans‐ and cis‐Limonene Oxides

The efficient hydrolytic kinetic separation of trans/cis‐(R)‐(+)‐limonene oxides was realized in a 1:1 mixed solvent of water and 1,4‐dioxane without additional catalyst. Optically pure trans‐(R)‐(+)‐limonene oxide was recovered in high yield (77%).     

Cationic photopolymerization of cis‐2,3‐tetramethylene‐1,4,6‐trioxaspiro[4,4]nonane

The spiro‐orthoester, cis‐2,3‐tetramethylene‐1,4,6‐trioxaspiro[4,4]nonane (cis‐TTN) ( I ), underwent rapid cationic photopolymerization when exposed to UV light using diphenyliodonium salts as a photoinitiator. The polymer, poly[(trans‐OCB)_x′‐(cis‐OCB)_x″‐(CHO)_y] thus formed consisted of poly(trans‐2‐oxycyclohexyl butanoate) (trans‐OCB)_x′ ( II ), poly(cis‐2‐oxycyclohexyl butanoate) (cis‐OCB)_x″ ( III ), and poly‐ (1,2‐cyclohexene oxide) (CHO)_y segments, and no expected pure poly(ether‐ester), that is, poly(2‐oxycyclohexyl butanoate), was isolated. The structure of the polymer was identified, and the mechanism of the reaction was deduced. The polymer thus formed exhibited expansion in volume during cationic photopolymerization when compared to that obtained by conventional cationic polymerization using a Lewis acid (e.g., BF₃OEt₂, CH₃OSO₂CF₃, or SnCl₄) as an initiator, which demonstrated volume shrinkage during polymerization. The volume expansion of the polymer during polymerization was due to (1) the lower content of the higher density (CHO)_y segment in the polymer chain and, more importantly, (2) the higher and optimal mole ratio of (trans‐OCB)_x′ and (cis‐OCB)_x″ segments that led the polymer in a more disordered, less dense, and higher volumetric state. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3680–3690, 2009     

Caesium cis‐tetrachloridodioxidorhenate(VII)

The title crystal structure, Cs[ReCl₄O₂], consists of cis‐tetrachloridodioxidorhenate(VII) anions and caesium cations. The distorted octahedral anion has nearly C_2v symmetry, with a cis arrangement of the oxide ligands. The Re—Cl bond lengths for the Cl atoms trans to the oxide ligands are affected by the trans influence of the Re—O bonds and are longer than for the Cl atoms cis to the oxide ligands [average of 2.472 (2) Åversus average of 2.322 (2) Å, respectively]. There are ten Cl atoms from six cis‐tetrachloridodioxidorhenate(VII) anions in the neighbourhood of the caesium cation.     

One Pot Synthesis of Medicinally Important cis‐2‐Methyl‐4‐amino substituted‐1,2,3,4‐tetrahydroquinolines

A simple synthesis of medicinally important cis‐2‐methyl‐4‐azapan‐2‐one‐1,2,3,4‐tetrahydroquinolines/cis‐9‐(2‐methyl‐1,2,3,4‐tetrahydroquinolin‐4‐yl)‐9H‐carbazole was reported. Multicomponent one pot synthesis with anilines and N‐vinylcaprolactam/N‐vinyl carbazole via imino Diels‐Alder reaction by using antimony trichloride as catalyst and acetonitrile as solvent was employed. NMR technique (2D) was used to study the regio‐ and stereo‐chemistry of newly synthesized compounds. The cis diastereo‐selectivity of the products was predicted by COSY and NOESY studies.     

A First Approach to the cis‐trans‐cis‐Photocyclodimers of 1,2‐Naphthoquinone

On irradiation (λ=350 nm), 1,2‐naphthoquinone (=naphthalene‐1,2‐dione) monoacetals 1 are converted quantitatively to mixtures of the cis‐trans‐cis‐photocyclodimers 2 and 3 . Careful hydrolysis of each of the (parent) pentacyclic diacetals 2a and 3a affords the – rather unstable – compounds 4 and 5 , respectively.     

A new polymorph of cis–transoid–cis‐dicyclohexano‐18‐crown‐6

A new orthorhombic polymorphic modification of the title compound (alternative name: cis–transoid–cis‐2,5,8,15,18,21‐hexaoxatri­cyclo­[20.4.0.0^9,14]­hexa­cosane), C₂₀H₃₆O₆, has been found and is compared with the previously known monoclinic modification. In the structures of the two polymorphs, the crown‐ether mol­ecules are centrosymmetric and reveal essen­tially the same molecular shape but different packing motifs.     

Total syntheses of (±)‐cis‐ and trans‐11‐methoxydeethyleburnamonine

The total syntheses of 11‐methoxydeethyleburnamonines ( 4 ) and ( 13 ) were carried out with use of 6‐methoxytryptophyl bromide ( 5 ) as starting material. Compound 5 was converted in three steps to trans‐ester 8 . Acid‐catalysed epimerization of 8 , lithium aluminum hydride reduction of the ester group, tosylation and substitution with cyanide gave the cis‐nitrile 12 . Acid‐induced cyclization of 12 yielded mainly (±)‐trans‐11‐methoxydeethyleburnamonine ( 13 ), whereas base‐induced cyclization gave (±)‐cis‐11‐methoxydeethyleburnamonine ( 4 ).     

13‐cis‐β,β‐Carotene and 15‐cis‐β,β‐carotene

13‐cis‐β,β‐Carotene, C₄₀H₅₆, crystallizes with a complete molecule in the asymmetric unit, whereas 15‐cis‐β,β‐carotene, also C₄₀H₅₆, has twofold symmetry about an axis through the central bond of the polyene chain. The polyene methyl groups are arranged on one side of the polyene chains for each molecule and the 6‐s‐cisβ end groups, with the cyclohexene rings in half‐chair conformations, are twisted out of the planes of the polyene chains by angles ranging from 41.37 (17) to 52.2 (4)°. The molecules in each structure pack so that the arms of one occupy the cleft of the next, and there is significant π–π stacking of the almost‐parallel polyene chains of the 15‐cis isomer, which approach at distances of 3.319 (1)–3.591 (1) Å.     

An Expeditious Access to Enantiomerically Pure cis‐Dialkyl‐Substituted γ‐ and δ‐Lactones

A facile general route to enantiomerically pure 3,4‐cis‐dialkyl‐substituted γ‐lactones and 4,5‐cis‐dialkyl‐substituted δ‐lactones by TiCl₄‐mediated Evans asymmetric aldolization as the key step is exemplified by synthesis of cis‐(3R,4R)‐3‐methyldecan‐4‐olide and (4R,5R)‐aerangis lactone.     

Semiempirical studies of ring twisting in cis‐stilbene and related biomolecules

The geometric and energetic predictions of the MNDO, AM1, and SAM1 models as they describe rotation of the dihedral angle between the plane of one of the phenyl rings and the plane of the olefin core of cis‐stilbene (cis‐1,2‐diphenylethylene) were tested for a variety of constraints. All three models predict that distortions away from the stable structure fixed by a compromise between π‐electron and steric repulsions lead to small (at most 1–2 kcal/mol) strain energies and geometry relaxations. Extensive peripheral substitution on the phenyl rings present in a prototype natural product having the cis‐stilbene structure, Combretastatin A‐4 (3,4,5‐trimethoxy‐3′‐hydroxy‐4′‐methoxy‐(Z)‐stilbene), distorted the shapes of the cis‐stilbene barriers to conformation change only minimally. It is concluded that natural products having the cis‐stilbene structure should be expected to interact with other biomolecules as if the phenyl twists are barrier free. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 71: 57–62, 1999     

Boronate affinity adsorption of cis‐diol‐containing biomolecules in nonaqueous solvent

Boronate affinity has attracted much attention in recent years. It has been broadly used for selective isolation and enrichment of cis‐diol‐containing molecules. Conventionally, the cis‐diols are adsorbed in mild alkaline aqueous solutions. In this work, for the first time, we found that boronate affinity adsorption could also be performed in nonaqueous solvent at nonbasic pH. Cis‐diol‐containing compounds present in herbal medicines were used for the adsorption test. The results indicated that all compounds obtained higher recoveries in the organic solvents (methanol, acetonitrile, ethyl acetate) compared with alkaline buffer. The adsorption of vicinal cis‐diol‐containing molecules in organic solvents could be accomplished rapidly, with high selectivity and high recoveries (>80%). These results shed light on the possibility of boronate affinity adsorption in nonaqueous solvents. The results are very important for the isolation and enrichment of cis‐diols, which have poor solubility in water, especially for those in herbal medicines. Copyright © 2015 John Wiley & Sons, Ltd.     

Homogeneous [RuIII(Me3tacn)Cl3]‐Catalyzed Alkene cis‐Dihydroxylation with Aqueous Hydrogen Peroxide

A simple and green method that uses [Ru(Me₃tacn)Cl₃] ( 1 ; Me₃tacn=N,N′,N′′‐trimethyl‐1,4,7‐triazacyclononane) as catalyst, aqueous H₂O₂ as the terminal oxidant, and Al₂O₃ and NaCl as additives is effective in the cis‐dihydroxylation of alkenes in aqueous tert‐butanol. Unfunctionalized alkenes, including cycloalkenes, aliphatic alkenes, and styrenes (14 examples) were selectively oxidized to their corresponding cis‐diols in good to excellent yield (70–96 %) based on substrate conversions of up to 100 %. The preparation of cis‐1,2‐cycloheptanediol (119 g, 91 % yield) and cis‐1,2‐cyclooctanediol (128 g, 92 % yield) from cycloheptene and cyclooctene, respectively, on the 1‐mol scale can be achieved by scaling up the reaction without modification. Results from Hammett correlation studies on the competitive oxidation of para‐substituted styrenes (ρ=?0.97, R=0.988) and the detection of the cycloadduct [(Me₃tacn)ClRuHO₂(C₈H₁₄)]⁺ by ESI‐MS for the 1 ‐catalyzed oxidation of cyclooctene to cis‐1,2‐cyclooctanediol are similar to those of the stoichiometric oxidation of alkenes by cis‐[(Me₃tacn)(CF₃CO₂)Ru^VIO₂]⁺ through [3+2] cycloaddition (W.‐P. Yip, W.‐Y. Yu, N. Zhu, C.‐M. Che, J. Am. Chem. Soc. 2005 , 127, 14239).     

Hydrogen bonding in polyamino‐polyalcohols: a monohydrated cocrystal of 1,3‐diamino‐5‐azaniumyl‐1,3,5‐trideoxy‐cis‐inositol iodide and 1,3,5‐triamino‐1,3,5‐trideoxy‐cis‐inositol

In the title monohydrated cocrystal, namely 1,3‐diamino‐5‐azaniumyl‐1,3,5‐trideoxy‐cis‐inositol iodide–1,3,5‐triamino‐1,3,5‐trideoxy‐cis‐inositol–water (1/1/1), C₆H₁₆N₃O₃⁺·I⁻·C₆H₁₅N₃O₃·H₂O, the neutral 1,3,5‐triamino‐1,3,5‐trideoxy‐cis‐inositol (taci) molecule and the monoprotonated 1,3‐diamino‐5‐azaniumyl‐1,3,5‐trideoxy‐cis‐inositol cation (Htaci⁺) both adopt a chair conformation, with the three O atoms in axial and the three N atoms in equatorial positions. The cation, but not the neutral taci unit, exhibits intramolecular O—H...O hydrogen bonding. The entire structure is stabilized by a complex three‐dimensional network of intermolecular hydrogen bonds. The neutral taci entities and the Htaci⁺ cations are each aligned into chains along [001]. In these chains, two O—H...N interactions generate a ten‐membered ring as the predominant structural motif. The rings consist of vicinal 2‐amino‐1‐hydroxyethylene units of neighbouring molecules, which are paired via centres of inversion. The chains are interconnected into undulating layers parallel to the ac plane, and the layers are further held together by O—H...N hydrogen bonds and additional interactions with the iodide counter‐anions and solvent water molecules.     

cis,cis‐Ceratospong­amide N,N‐di­methyl­acet­amide hemisolvate in the presence of twinning

Ceratospong­amide (CS) is a potent inhibitor of secreted phospho­lipase A₂, and cis,cis and trans,trans isomers, related with respect to the two proline amide bonds, are known. Crystals of cis,cis‐CS were grown from N,N‐di­methyl­acet­amide solution, giving the title compound, the cyclic ester of isoleucyl­oxazolinyl­phenyl­alanyl­prolyl­thia­zolyl­phenyl­alanyl­pro­line [cyclo(‐Ile–Oxz–Phe–Pro–Thz–Phe–Pro‐)] N,N‐di­methyl­acet­amide hemisolvate, C₄₁H₄₉N₇O₆S·0.5C₄H₉NO. The structure is the third example of cis,cis‐CS to be investigated and comprises twinned crystals, in which the a and b axes are interchanged. The ratio of co‐existing twin crystals is approximately 50%. The peptide has a `saddle‐like' structure and is very similar to previously reported structures of cis,cis‐CS, which implies that the structure of cis,cis‐CS is very stable in spite of differences in crystallization conditions.