A Straightforward Synthesis of 2‐[1‐Alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic Acid Derivatives via Domino Michael Addition?Cyclization Reaction

A new and efficient synthesis of 2‐[1‐alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic acid derivatives by a one‐pot three‐component reaction between primary amine, dialkyl acetylenedicarboxylate, and itaconic anhydride (=3,4‐dihydro‐3‐methylidenefuran‐2,5‐dione) is reported. The reaction was performed without catalyst and under solvent‐free conditions with excellent yields. Notably, the ready availability of the starting materials, and the high level of practicability of the reaction and workup make this approach an attractive complementary method to access to unknown 2‐[1‐alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic acid derivatives. The structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of domino Michael addition? cyclization reaction is proposed (Scheme 2).     

Partial Hydrolysis of Poly(2‐ethyl‐2‐oxazoline) and Potential Implications for Biomedical Applications?

The hydrolysis of PEtOx is studied to evaluate the potential toxicity of partially hydrolyzed polymers that might interfere with its increasing popularity for biomedical applications. The hydrolysis of PEtOx is studied in the presence of digestive enzymes (gastric and intestinal) and at 5.8 M hydrochloric acid as a function of temperature (57, 73, 90, and 100 °C). It is found that PEtOx undergoes negligible hydrolysis at 37 °C and that thermal and solution properties are not altered when up to 10% of the polymer backbone is hydrolyzed. Mucosal irritation and cytotoxicity is also absent up to 10% hydrolysis levels. In conclusion, PEtOx will not decompose at physiological conditions, and partial hydrolysis will not limit its biomedical applications.

     

Bis(4‐picoline‐κN)gold(I) dibromidoaurate(I) and bis(4‐picoline‐κN)gold(I) dichloridoaurate(I): space‐group ambiguity?

Bis(4‐picoline‐κN)gold(I) dibromidoaurate(I), [Au(C₆H₇N)₂][AuBr₂], (I), crystallizes in the monoclinic space group P2₁/n, with two half cations and one general anion in the asymmetric unit. The cations, located on centres of inversion, assemble to form chains parallel to the a axis, but there are no significant contacts between the cations. Cohesion is provided by flanking anions, which are connected to the cations by short Au...Au contacts and C—H...Br hydrogen bonds, and to each other by Br...Br contacts. The corresponding chloride derivative, [Au(C₆H₇N)₂][AuCl₂], (II), is isotypic. A previous structure determination of (II), reported in the space group P with very similar axis lengths to those of (I) [Lin et al. (2008). Inorg. Chem. 47 , 2543–2551], might be identical to the structure presented here, except that its γ angle of 88.79 (7)° seems to rule out a monoclinic cell. No phase transformation of (II) could be detected on the basis of data sets recorded at 100, 200 and 295 K.     

Formation of Trinuclear Rhodium‐Hydride Complexes [{Rh(PP*)H}3‐ (μ2‐H)3(μ3‐H)][anion]2—During Asymmetric Hydrogenation?

Recently described and fully characterized trinuclear rhodium‐hydride complexes [{Rh(PP*)H}₃(μ₂‐H)₃(μ₃‐H)][anion]₂ have been investigated with respect to their formation and role under the conditions of asymmetric hydrogenation. Catalyst–substrate complexes with mac (methyl (Z)‐ N‐acetylaminocinnamate) ([Rh(tBu‐BisP*)(mac)]BF₄, [Rh(Tangphos)(mac)]BF₄, [Rh(Me‐BPE)(mac)]BF₄, [Rh(DCPE)(mac)]BF₄, [Rh(DCPB)(mac)]BF₄), as well as rhodium‐hydride species, both mono‐([Rh(Tangphos)‐ H₂(MeOH)₂]BF₄, [Rh(Me‐BPE)H₂(MeOH)₂]BF₄), and dinuclear ([{Rh(DCPE)H}₂(μ₂‐H)₃]BF₄, [{Rh(DCPB)H}₂(μ₂‐H)₃]BF₄), are described. A plausible reaction sequence for the formation of the trinuclear rhodium‐hydride complexes is discussed. Evidence is provided that the presence of multinuclear rhodium‐hydride complexes should be taken into account when discussing the mechanism of rhodium‐promoted asymmetric hydrogenation.     

Synthesis of Perfluoroalkyl‐Substituted γ‐Lactones and 4,5‐Dihydropyridazin‐3(2H)‐ones via Donor?Acceptor Cyclopropanes

Rh₂(OAc)₄‐Catalyzed decomposition of diazo esters in the presence of perfluoroalkyl‐ or perfluoroaryl‐substituted silyl enol ethers smoothly provided the corresponding alkyl 2‐siloxycyclopropanecarboxylates in very good yields. The generated donor? acceptor cyclopropanes are equivalents of γ‐oxo esters, which we demonstrated by their one‐pot transformations to yield fluorine‐containing heterocycles. A reductive procedure selectively afforded perfluoroalkyl‐substituted γ‐hydroxy esters or γ‐lactones. The treatment of the donor? acceptor cyclopropanes with hydrazine or phenylhydrazine afforded a series of perfluoroalkyl‐ and perfluoroaryl‐substituted 4,5‐dihydropyridazin‐3(2H)‐ones.     

Isostructural or not? Adducts of some aryl­tin halides with (E)‐1,2‐bis(4‐pyridyl)­ethene

The title complexes [μ‐(E)‐4,4′‐(ethene‐1,2‐diyl)­di­pyridine‐κ²N:N′]­bis­[halotris(4‐methyl­phenyl)­tin(IV)], [Sn₂(C₇H₇)₆X₂(C₁₂H₁₀N₂)], where halo is chloro (X = Cl) and bromo (X = Br) are isostructural. In both crystals, the mol­ecules lie on inversion centers, and there are voids of ca 80 ų that could, but apparently do not, accommodate water mol­ecules. The corresponding iodo structure (X = I) is almost, but not quite, isostructural with the other two compounds; when Br is changed to I, the length of the c axis decreases by more than 1 Å and the voids are no longer large enough to accomodate any solvent mol­ecule. The related complex [μ‐(E)‐4,4′‐(ethene‐1,2‐diyl)­di­pyridine‐κ²N:N′]­bis­[chloro­tri­phenyl­tin(IV)], [Sn₂(C₆H₅)₆Cl₂(C₁₂H₁₀N₂)], crystallizes in a related structure, but the mol­ecules lie on general rather than on special positions. The molecular structures of the four complexes are similar, but the conformation of the phenyl derivative is approximately eclipsed rather than staggered.     

2‐Halogeno‐1,3,2‐diazaarsolenes and 2‐halogeno‐1,3,2‐diazastibolenes: Examples for spontaneous E?X bond heterolysis or not?

2‐X‐1,3,2‐diazaarsolenes and 2‐X‐1,3,2‐ stibolenes (X = Cl, Br) were prepared from appropriate α‐amino‐aldimine precursors via transamination with ClSb(NMe₂)₂ or via base‐induced dehydrohalogenation with EX₃ (E = As, Sb). The products were further converted into 2‐iodo‐derivatives via halide exchange with Me₃SiI, or into 1,3,2‐diazaarsolenium or 1,3,2‐stibolenium salts via halide abstraction using E′X₃ (E′ = Al, Ga, Sb) or Me₃SiOTf. All compounds synthesized were characterized by spectroscopic data and several of them by single‐crystal X‐ray diffraction studies. The results of these investigations confirmed that diazaarsolenium or stibolenium cations are stabilized by similar π‐delocalization effects as the corresponding diazaphospholenium cations. 2‐Halogeno‐1,3,2‐diazaarsolenes and 2‐halogeno‐132‐stibolenes are best addressed as molecular species whose covalent E X bonds are as in 2‐chloro‐diazaphospholenes weakened by intramolecular π(C₂N₂) → σ*(E X) and, in the case of the Sb‐containing heterocycles, inter‐ molecular n(X′) → σ*(E X) hyperconjugation between the σ* (E X) orbital and a lone‐pair of electrons on the halogen atom of a neighboring molecule. Correlation of structural and spectroscopic data and the evaluation of halide transfer reactions allowed to conclude that the extent of E X bond weakening in the 2‐X‐substituted heterocycles decreases and thus the Lewis acidity of the cations increases, with increasing atomic number of the pnicogen atom. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:327–338, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20098     

Access to β‐Lactams by Enantioselective Palladium(0)‐Catalyzed C(sp3)?H Alkylation

β‐Lactams are very important structural motifs because of their broad biological activities as well as their propensity to engage in ring‐opening reactions. Transition‐metal‐catalyzed C H functionalizations have emerged as strategy enabling yet uncommon highly efficient disconnections. In contrast to the significant progress of Pd⁰‐catalyzed C H functionalization for aryl–aryl couplings, related reactions involving the formation of saturated C(sp³) C(sp³) bonds are elusive. Reported here is an asymmetric C H functionalization approach to β‐lactams using readily accessible chloroacetamide substrates. Important aspects of this transformation are challenging C(sp³) C(sp³) and strain‐building reductive eliminations to for the four‐membered ring. In general, the β‐lactams are formed in excellent yields and enantioselectivities using a bulky taddol phosphoramidite ligand in combination with adamantyl carboxylic acid as cocatalyst.     

Microwave Accelerated Polymerization of 2‐Phenyl‐2‐oxazoline: Microwave or Temperature Effects?

Summary: Investigations regarding the cationic ring‐opening polymerization of 2‐phenyl‐2‐oxazoline under microwave irradiation and conventional heating are reported. This study was inspired by contradictory reports of the (non‐)existence of non‐thermal microwave effects that might accelerate the cationic ring‐opening of 2‐oxazolines. The polymerization of 2‐phenyl‐2‐oxazoline was investigated under pressure in acetonitrile and under reflux (or at the boiling point of butyronitrile in a closed vessel) in butyronitrile utilizing a single‐mode microwave reactor and automated synthesis robots with conventional heating.

     

Temperature‐Dependent Product Selectivity in the Vilsmeier?Haack Reaction on Bis(phenylhydrazones) of Bis(aroylmethyl) Sulfides (=1,1′‐[Thiobis(methylene)]bis[arylmethanone] Bis(2‐phenylhydrazones)): Synthesis of 3‐Aroylindoles (=Aryl(1H‐indol‐3‐yl)methanones)

The bis(phenylhydrazone) of substituted diphenacyl sulfides (=1,1′‐[thiobis(methylene)]bis[arylmethanone] bis(2‐phenylhydrazones)) 1 underwent a tandem sequence of reactions upon treatment with Vilsmeier reagent, ultimately yielding 3‐aroylindoles (=aryl(1H‐indol‐3‐yl)methanones) 3 (Scheme 1 and Table 1). The reaction seems to be product selective depending upon the reaction temperature.