Octahydrocyclopenta[c]pyridine Scaffold – Enantioselective Synthesis and Indole Annulation

An optically active hexahydrocyclopenta[c]pyridine derivative with quaternary stereocenter was prepared as a new heterocyclic scaffold. Key reaction was the Pd‐catalyzed asymmetric allylic alkylation of a piperidine‐based β‐oxoester, which proceeded in very good yield with high level of enantioselectivity (90 %, 95 % ee). The α‐allyl moiety was transformed into a 1,4‐diketone by Pd‐catalyzed Wacker oxidation with molecular oxygen (89 %). This intermediate was cyclized in an intramolecular aldol reaction furnishing the cyclopentenone motif (86 %). Hydrogenation of the C–C double bond gave the cis‐annulated octahydrocyclopenta[c]pyridine (86 %), which was submitted to Fischer indolization (85 %). Although two regioisomers could be expected, only the angular constitution was observed. Relative and absolute configurations were established by X‐ray crystallography of a para‐iodo benzamide derivative. The utility of the title compound as scaffold is further highlighted by a number of synthetically useful transformations, for instance formation of carboxamides, sulfonamides, ureas and reductive aminations with aldehydes

Octahydrocyclopenta[c]pyridine Scaffold – Enantioselective Synthesis and Indole Annulation

An optically active hexahydrocyclopenta[c]pyridine derivative with quaternary stereocenter was prepared as a new heterocyclic scaffold. Key reaction was the Pd‐catalyzed asymmetric allylic alkylation of a piperidine‐based β‐oxoester, which proceeded in very good yield with high level of enantioselectivity (90 %, 95 % ee). The α‐allyl moiety was transformed into a 1,4‐diketone by Pd‐catalyzed Wacker oxidation with molecular oxygen (89 %). This intermediate was cyclized in an intramolecular aldol reaction furnishing the cyclopentenone motif (86 %). Hydrogenation of the C–C double bond gave the cis‐annulated octahydrocyclopenta[c]pyridine (86 %), which was submitted to Fischer indolization (85 %). Although two regioisomers could be expected, only the angular constitution was observed. Relative and absolute configurations were established by X‐ray crystallography of a para‐iodo benzamide derivative. The utility of the title compound as scaffold is further highlighted by a number of synthetically useful transformations, for instance formation of carboxamides, sulfonamides, ureas and reductive aminations with aldehydes

Synthesis of Aromatic and Aliphatic Di-, Tri-, and Tetrasulfonic Acids

Oligosulfonic acids are promising linker compounds for coordination polymers and metal-organic frameworks, however, compared to their carboxylic acid congeners, often not readily accessible by established synthetic routes. This Account highlights the synthesis of recently developed aromatic and aliphatic di-, tri- and tetrasulfonic acids. While multiple electrophilic sulfonations of aromatic substrates are rather limited, the nucleophilic aromatic substitution including an intramolecular variant, the Newman-Kwart rearrangement, allows the flexible introduction of up to four sulfur-containing moieties at an aromatic ring. Sulfonic acids are then accessed by oxidation of thiols, thioethers, or thioesters either directly with hydrogen peroxide or in two steps with chlorine (generated in situ from N-chlorosuccinimide/hydrochloric acid) to furnish sulfochlorides which are subsequently hydrolyzed. In the aliphatic series, secondary alcohols as starting materials are converted into thioethers, thioesters, or thiocarbonates by nucleophilic substitutions, which are also subsequently oxidized to furnish sulfonic acids

Biphenyl Sulfonic and Disulfonic Acids with Perfluorinated Alkyl Residues

Sulfonic acids serve as interesting, yet not intensively studied alternatives to carboxylic acids as linker units in coordination polymers. In this study, we present the synthesis of hybrid sulfonic acids with polar, rigid biphenyl moieties and disordered highly fluorinated alkyl chains. Consequently, eight biphenyl sulfonic and disulfonic acids with one or two perfluoroalkyl chains were prepared. The key steps within the synthesis include two palladium catalyzed C-C bond formations: The perfluoroalkyl residue is installed by Heck reaction (up to 91 %) using 1H,1H,2H-perfluorinated alkenes (C-6 and C-8) and the biphenyl unit is established by a Suzuki coupling (up to 88 %) of boronic acids bearing one or two protected thiol groups. Finally, these thiol groups are converted into the sulfonic acids by N-chlorosuccinimide mediated oxidation followed by hydrolysis of the respective sulfonyl chloride

Tripodal methanetrisulfonate ligands in the trinuclear complex {Ni-3[CH(SO3)(3)](2)(NMP)(8)}

The reaction of Ni(OH)(2) and methanetrisulfonic acid trihydrate CH(SO3H)(3)center dot 3H(2)O (H(3)MTA center dot 3H(2)O) in N-methyl-pyrrolidone (NMP) leads to the trinuclear complex {Ni-3[MTA](2)(NMP)(8)] (triclinic, P (1) over bar, Z=1, a =946.25(3), b= 1073.24(3), c= 1518.27(4) pm, alpha = 72.193(2), beta = 87398(2), gamma = 89.389(2)degrees, V = 1466.49(7) x 10(6) pm(3)). The structural features of the methanetrisulfonate anions are tripodal as well as chelating coordination of the Ni2+ ions. The thermal analysis has shown that the compound is first losing NMP molecules and that the solvent-free methanetrisulfonate finally decomposes yielding Ni3S2

Orthogonally Protected Diaminoterephthalate Scaffolds: Installation of Two Functional Units at the Chromophore

The 2,5-diaminoterephthalate structural motif is a powerful chromophore with remarkable fluorescence properties. Containing two carboxylate and two amino functions, it defines a colored molecular scaffold which allows for orthogonal functionalization with different functional units. Therefore, different applications in life sciences and materials science could be addressed. In this study, the two amino functions were alkylated by reductive amination with side chains carrying amino (orthogonally protected as Boc or Alloc) and carboxylate functions (orthogonally protected as <i>t</i>Bu or allyl ester). After sequential deprotections, functional units were introduced by amidation reactions. As three examples, the chromophore was coupled with retinoic acid and fullerene C₆₀ in order to obtain a triad for studying photoinduced electron transfer processes. Furthermore, cyclooctyne and azide moieties were introduced as functional units, allowing for ligation by click reactions. These two clickable groups were applied in combination with maleimide units which are reactive toward thiol residues. The latter dyes define so-called “turn on” probes, since the fluorescence quantum yields increased by one order of magnitude upon reaction with the molecular target

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

Two bifunctional diaminoterephthalate (DAT) fluorescence dyes were prepared in a three-step sequence including one deprotection reaction. One functional unit is α-lipoic acid (ALA) for binding the dye to gold surfaces. It was introduced to the DAT scaffold by an amidation reaction. The other functional unit is a para-(trifluoromethyl)benzyl group for facile detection of the surface-bound material by X-ray photoelectron spectroscopy (XPS). This residue was introduced by reductive amination of the DAT scaffold with the respective benzaldehyde derivative. In one compound (60% yield over three steps) the ALA unit is directly bound to the DAT as a relatively electron-withdrawing amide. In solution (CH2Cl2), this material shows strong fluorescence (quantum yield 57% with emission at 495 nm, absorption maximum at 420 nm). The other compound (57% yield over three steps) possesses a propylene spacer between the ALA and the DAT units for electronic decoupling, thus, bathochromic shifts are observed (absorption at 514 nm, emission at 566 nm). The quantum yield is, however, lower (4%). Self-assembled monolayers on a gold surface of both compounds were prepared and characterized by high-resolution XPS of the C 1s, O 1s, S 2p, N 1s and F 1s emissions. The high signal-to-noise ratios of the F 1s peaks indicated that trifluoromethylation is an excellent tool for the detection of surface-bound materials by XPS