Palladium‐Catalyzed Formal Hydroalkylation of Aryl‐Substituted Alkynes with Hydrazones

We have developed an unprecedented Pd‐catalyzed formal hydroalkylation of alkynes with hydrazones, which are generated in situ from naturally abundant aldehydes, as both alkylation reagents and hydrogen donors. The hydroalkylation proceeds with high regio‐ and stereoselectivity to form (Z)‐alkenes, which are more difficult to generate compared to (E)‐alkenes. The reaction is compatible with a wide range of functional groups, including hydroxy, ester, ketone, nitrile, boronic ester, amine, and halide groups. Furthermore, late‐stage modifications of natural products and pharmaceutical derivatives exemplify its unique chemoselectivity, regioselectivity, and synthetic applicability. Mechanistic studies indicate the possible involvement of Pd‐hydride intermediates.     

Characterization of linear and branched polyacrylates by tandem mass spectrometry

The unimolecular degradation of alkali-metal cationized polyacrylates with the repeat unit CH₂CH(COOR) and a variety of ester pendants has been examined by tandem mass spectrometry. The fragmentation patterns resulting from collisionally activated dissociation depend sensitively on the size of the ester alkyl substituent (R). With small alkyl groups, as in poly(methyl acrylate), lithiated or sodiated oligomers (M) decompose via free-radical chemistry, initiated by random homolytic C-C bond cleavages along the polymer chain. The radical ions formed this way dissociate further by backbiting rearrangements and β scissions to yield a distribution of terminal fragments with one of the original end groups and internal fragments with 2–3 repeat units. If the ester alkyl group bears three or more carbon atoms, cleavages within the ester moieties become the predominant decomposition channel. This distinct reactivity is observed if R = t-butyl, n-butyl, or the mesogenic group (CH₂)₁₁-O-C₆H₄-C₆H₄-CN. The [M+alkali metal]⁺ ions of the latter polyacrylates dissociate largely by charge-remote 1,5-H rearrangements that convert COOR to COOH groups by expulsion of 1-alkenes. The acid groups may displace an alcohol unit from a neighboring ester pendant to form a cyclic anhydride, unless hindered by steric effects. Using atom transfer radical polymerization, hyperbranched polyacrylates were prepared carrying ester groups both within and between the branches. Unique alkenes and alcohols are cleaved from ester groups at the branching points, enabling determination of the branching architecture. Figure MALDI-CAD tandem mass spectrum of the lithiated 4-mer from a hyperbranched polyacrylate. The fragments marked by green stars diagnose the branched architecture shown on top of the spectrum. The fragments marked by violet stars diagnose a different isomer.     

Field ionization mass spectrometry of higher n-alkenes

In a strong electric field the molecular ions of n-alkenes ≤C-12 decompose via cleavage of the C? C bond β to the double bond to form the characteristic alkenyl ions that may be used for the identification of positional isomers. For 3-alkenes (>C-10), 4-, 5- and 6-alkenes the formation of the ions with m/e 54 via double β-cleavage is typical. The field ionization mass spectra of the cis and trans isomers are indistinguishable.     

Palladium-catalyzed intramolecular hydroalkylation of alkenyl-beta-keto esters, alpha-aryl ketones, and alkyl ketones in the presence of Me3SiCl or HCl

Reaction of 3-butenyl beta-keto esters or 3-butenyl alpha-aryl ketones with a catalytic amount of [PdCl2(CH3CN)2] (2) and a stoichiometric amount of Me3SiCl or Me3SiCl/CuCl2 in dioxane at 25-70 degrees C formed 2-substituted cyclohexanones in good yield with high regioselectivity. This protocol tolerated a number of ester and aryl groups and tolerated substitution at the allylic, enolic, and cis and trans terminal olefinic positions. In situ NMR experiments indicated that the chlorosilane was not directly involved in palladium-catalyzed hydroalkylation, but rather served as a source of HCl, which presumably catalyzes enolization of the ketone. Identification of HCl as the active promoter of palladium-catalyzed hydroalkylation led to the development of an effective protocol for the hydroalkylation of alkyl 3-butenyl ketones that employed sub-stoichiometric amounts of 2, HCl, and CuCl2 in a sealed tube at 70 degrees C.     

Electrochemical polymerization of dicarboxylic acids—II. Oligomers and side products in the polymerization of adipic acid

The electrochemical polymerization of adipic acid in methanol and in methanol-pyridine (1:1) via the Kolbe reaction

was investigated as regards the oligomeric and side products. GC-MS, i.r. and NMR were used to identify the many products. Gaseous and volatile compounds were identified as C₄ and C₈ hydrocarbons besides λ- and δ-valerolactones. The less volatile compounds were separated on silica gel columns to fractions, viz. that eluted by heptane which contained hydrocarbons, that eluted by benzene which contained ether and ester groups and that eluted by methanol which contained higher oligomeric products containing oxygen. Four types of hydrocarbons were formed, viz.n-alkanes, n-alkenes, x-alkenes (the place of the double bond is not known) and cycloalkanes. Saturated and unsaturated oligomeric mono- and di-carboxylic acids were also formed.     

Metathesis of silicon-containing olefins: IX. Synthesis of 1-(trimethylsilyl)-1-alkenes by olefin metathesis

1-(Trimethylsilyl)-1-alkenes of general formula CH₃(CH₂)_nCH?CHSi(CH₃)₃, where n = 3–15, have been prepared by a novel method, viz. by an effective cross-metathesis of vinyltrimethylsilane with 1-alkenes catalyzed by RuCl₂(PPh₃)₃. Excess of 1-alkene in the reaction mixture gave 1-(trimethylsilyl)-1-alkenes in good yields of up to 60% (in terms of vinylsilane). The products were identified by NMR spectroscopic (¹H, ¹³C NMR) and GC MS methods.     

Temperature effects on 13C n.m.r. chemical shifts of normal alkanes and some line r and branched 1-alkenes

¹³C n.m.r. chemical shifts of a number of 1,1-disubstituted ethylenes are presented. Moreover, effects of changing temperatures on the ¹³C n.m.r. chemical shifts of some of these compounds as well as of three normal alkanes are given. These variations in chemical shifts are attributed to varying amounts of sterically induced shifts in the different conformational equilibria. In addition to the well-known 1,4 interaction between two alkyl groups shielding effects on the carbon atoms of the connecting bonds are also proposed. No definite explanation of this effect is presented at this time. It is further shown that no simple correlations exist between ¹³C n.m.r. chemical shifts and calculated total charge densities at this level. Instead, the experimental results in 1-alkenes are rationalized by assuming a linear dependence of the ¹³C n.m.r. chemical shifts of C-1 and C-2 via rehybridizations on changes in bond angles for small skeletal deformations caused by steric interactions. These changes in geometries, as well as conformational energies in three 1-alkenes, were calculated by means of VFF calculations. Finally. upfield shifts for both C-2 and C-4 are proposed for those conformations of 1-alkenes in which the C-3? C-4 group interacts with the p_z-orbital of C-2.     

Formation of C(sp3)–C(sp3) Bonds through Nickel‐Catalyzed Decarboxylative Olefin Hydroalkylation Reactions

Olefins and carboxylic acids are among the most important feedstock compounds. They are commonly found in natural products and drug molecules. We report a new reaction of nickel‐catalyzed decarboxylative olefin hydroalkylation, which provides a novel practical strategy for the construction of C(sp³)?C(sp³) bonds. This reaction can tolerate a variety of synthetically relevant functional groups and shows good chemo‐ and regioselectivity. It enables cross‐coupling of complex organic molecules containing olefin groups and carboxylic acid groups in a convergent fashion.     

Enantio- and Diastereoselective NiH-Catalyzed Hydroalkylation of Enamides or Enecarbamates with Racemic α-Bromoamides**

Catalytic methods which control multiple stereogenic centers simultaneously are highly desirable in modern organic synthesis and chemical manufacturing. Herein, we report a regio-, enantio-, and diastereoselective NiH-catalyzed hydroalkylation process which proceeds with simultaneous control of vicinal stereocenters originating from two readily accessible partners, prochiral internal alkenes (enamides or enecarbamates) and racemic alkyl electrophiles (α-bromoamides or Katritzky salts). This reaction produces high-value β-aminoamides and their derivatives under mild conditions and with precise selectivity. Preliminary studies of the mechanism indicate that the reaction involves an enantioselective syn-hydronickelation to generate an enantiomerically enriched alkylnickel(II) species. Subsequent enantioconvergent alkylation with a racemic alkyl electrophile generates the desired product as a single stereoisomer.     

Photoredox- and Nickel-Catalyzed Hydroalkylation of Alkynes with 4-Alkyl-1,4-dihydropyridines: Ligand-Controlled Regioselectivity

Dual photoredox- and nickel-catalyzed hydroalkylation of terminal alkynes with 4-alkyl-1,4-dihydropyridines under visible light irradiation to afford Markovnikov- or anti-Markovnikov-type alkylated alkenes in good-to-high yields has been achieved, in which the regioselectivity of the products was effectively controlled by coordination ligands for nickel species. Using [NiCl₂(dtbbpy)] as a catalyst led to the formation of Markovnikov-type products, whereas using NiCl₂ ⋅ 6 H₂O led to the formation of anti-Markovnikov-type products.     

Alkyl Formates as Transfer Hydroalkylation Reagents and Their Use in the Catalytic Conversion of Imines to Alkylamines**

Easily accessible via a simple esterification of alcohols with formic acid, alkyl formates are used as a novel class of transfer hydroalkylation reagents, CO₂ acting as a traceless linker. As a proof-of-concept, their reactivity in the transfer hydroalkylation of imines is investigated, using a ruthenium-based catalyst and LiI as promoter to cleave the C−O σ-bond of the formate scaffold. Providing tertiary amines, the reaction displays a divergent regioselectivity compared to previously reported transfer hydroalkylation strategies.     

Use of carbowax 20M glass capillary columns below their lower temperature limit

The optimal separation properties of Carbowax 20M as a stationary phase in 300-m glass capillary columns at temeperatures below its lower temperature limit (60°) in terms of the selectivity, efficiency and speed of the gas chromatographic analysis of isomeric C₁₀---₁₃n-alkenes were investigated.In the separation of isomeric n-alkenes two possible states of the Carbowax stationary phase below 60° were used (solid state and intermediate liquid state), and the dependence of the retention of the isomers on temperature was studied. The region of the hysteresis portion of the I^CW = f(T)diagram permits the continuous setting of column selectivity. The efficiency of the column at temperatures below the lower temperature limit of Carbowax 20M depends on the spatial cis-trans configuration of n-alkenes and, in the solid state, for cis-isomers is comparable to the high efficiency of this column at higher temperatures (115°). Utilization of Carbowax 20M in the solid state made it possible to achieve faster and more complete separations of the eleven possible positional and spatial isomers of n-tridecenes in comparison with previous methods.     

Rate constants for the gas-phase reaction of C5?C10 alkenes with ozone

The gas-phase reaction of ozone with C₅? C₁₀ alkenes(eight 1-alkenes, four 1,1-disubstituted alkenes, and cyclohexene) has been investigated at atmospheric pressure and ambient temperature (285–293 K). Cyclohexane was added to scavenge the hydroxyl radical, which forms as a product of the ozone-alkene reaction. The reaction rate constants, in units of 10^?18 cm³ molecule^?1 s^?1, are 9.6±1.6 for 1-pentene, 9.7±1.4 for 1-hexene, 9.4±0.4 for 1-heptene, 12.5±0.4 for 1-octene, 8.0±1.4 for 1-decene, 3.8±0.6 for 3-methyl-1-pentene, 7.3±0.7 for 4-methyl-1-pentene, 3.9±0.9 for 3,3-dimethyl-1-butene, 13.3±1.4 for 2-methyl-1-butene, 12.5±1.1 for 2-methyl-1-pentene, 10.0±0.3 for 2,3-dimethyl-1-butene, 13.7±0.9 for 2-ethyl-1-butene, and 84.6±1.0 for cyclohexene. Substituent effects on alkene reactivity are examined. Steric effect appear to be important for all 1,1-disubstituted alkenes as well as for those 1-alkenes that bear s-butyl and t-butyl groups. The results are briefly discussed with respect to the atomospheric persistence of the alkenes studied. © 1995 John Wiley & Sons, Inc.     

Synthesis of imidazo[1,5-a]pyridines from 1,1-dibromo-1-alkenes

An efficient method is developed for the synthesis of imidazo[1,5-a]pyridine from the reaction of 1,1-dibromo-1-alkenes with 2-aminomethylpyridines. The reaction requires an inorganic base, such as Na₂CO₃, and moderate heating in DMF to proceed. Moderate to good yields are obtained. As demonstrated by the authors and others, 1,1-dibromo-1-alkenes are employed as synthons for activated carboxyl groups.     

Cobalt-Catalyzed Facial-Selective Hydroalkylation of Cyclopropenes

Cyclopropene hydrofunctionalization has been a promising strategy for accessing multi-substituted cyclopropanes; however, cyclopropene hydroalkylation remains underdeveloped. Herein, we report a low-valent CoH-catalyzed facial-selective cyclopropene hydroalkylation to access multi-substituted cyclopropanes. This reaction exhibits a broad substrate scope of alkyl halides and cyclopropenes and tolerates many functional groups. Moderate-to-good facial-selectivity is obtained without any directing groups. Mechanism studies provide evidence that alkyl radicals are generated from alkyl halides and irreversible CoH insertion is responsible for the facial-selectivity. Our preliminary exploration demonstrates that asymmetric cyclopropene hydroalkylation can be realized without conspicuous auxiliary groups.     

Crystallization and crystal structure of poly(ester amide)s derived from L‐tartaric acid

The crystal structure and crystallization behavior of a series of poly(ester amide)s derived from L ‐tartaric acid, 1,6‐hexanediamine, and 6‐amino‐1‐hexanol were examined. The study included aregic polymers containing 5, 10, and 20% of ester groups in addition to the syndioregic polymer containing equal amounts of amide and ester groups. X‐ray diffraction data revealed that all the aregic poly(ester amide)s adopt the same crystal structure as the parent polyamide made of L ‐tartaric acid, and 1,6‐hexanediamine. In this structure, chains are slightly compressed and arranged as in the α‐form of nylon 66. Solid‐state nuclear magnetic resonance (NMR) revealed that ester groups are excluded from the crystal phase except for the case of the syndioregic polymer. Isothermal crystallization kinetics was analyzed according to the Avrami theory. Crystallization rates were found to decrease regularly with increasing contents in ester groups and with increasing crystallization temperature. Avrami exponent values close to 2 were found whereas spherulitic morphologies were observed by optical microscopy. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 116–125, 2007     

A Simple Nickel Catalyst Enabling an E-Selective Alkyne Semihydrogenation

Stereoselective alkyne semihydrogenations are attractive approaches to alkenes, which are key building blocks for synthesis. With regards to the most atom-economic reducing agent dihydrogen (H₂), only few catalysts for the challenging E-selective alkyne semihydrogenation have been disclosed, each with a unique substrate scope profile. Here, we show that a commercially available nickel catalyst facilitates the E-selective alkyne semihydrogenation of a wide variety of substituted internal alkynes. This results in a simple and broadly applicable overall protocol to stereoselectively access E-alkenes employing H₂, which could serve as a general method for synthesis.     

Stereoselective Synthesis of (Z)-Perfluoroalkyl-1-iodo-1-triisopropyl Silylalkenes: A Convenient Route to Perfluoroalkyl-Substituted Unsaturated Synthons

The quantitative and fully stereoselective synthesis of (Z)-perfluoroalkyl-1-iodo-1-triisopropylsilylalkenes and their easy, high-yielding transformation into the corresponding 1-iodo-2-perfluoroacetylenes and (Z)-2-perfluoroalkyl-1-iodo-1-alkenes, compounds of interest as synthons for classical organometallic chemistry or for metal-catalyzed coupling reactions, are discussed.     

Ene reaction of α-thiocarbocation: Simple synthesis of E,E-2,4-alkadienoic esters from 1-alkenes

Pummerer reaction intermediate $\text{2}$ of α-methylsulfinylacetate ($\text{1}$) has been found to react with 1-alkenes to afford ene adducts $\text{3}$. E,E-2,4-decadienoic ester ($\text{5}$) was synthesized from the adduct $\text{3}$ (n=5).     

Two‐ and Three‐Component Reactions Leading to New Enamines Derived from 2,3‐Dicyanobut‐2‐enoates

The three‐component reactions of 1‐azabicyclo[1.1.0]butanes 1 , dicyanofumarates (E)‐ 5 , and MeOH or morpholine yielded azetidine enamines 8 and 9 with the cis‐orientation of the ester groups at the C?C bond ((E)‐configuration; Schemes 3 and 4). The structures of 8a and 9d were confirmed by X‐ray crystallography. The formation of the products is explained via the nucleophilic addition of 1 onto (E)‐ 5 , leading to a zwitterion of type 7 (Scheme 2), which is subsequently trapped by MeOH or morpholine ( 10a ), followed by elimination of HCN. Similarly, two‐component reactions between secondary amines 10a – 10c and (E)‐ 5 gave products 12 with an (E)‐enamine structure and (Z)‐oriented ester groups. On the other hand, two‐component reactions involving primary amines 10d – 10f or NH₃ led to the formation of the corresponding (Z)‐enamines, in which the (E)‐orientation of ester groups was established.