Christian Mück-Lichtenfeld

6‐Trifluoromethyl‐Phenanthridines through Radical Trifluoromethylation of Isonitriles

The trifluoromethyl group can be found in many drugs or drug candidates. Chemical and physical properties of biologically active compounds are altered upon incorporation of the CF3 group. The higher solubility and lipophilicity exerted by the fluorinated methyl group lead to better membrane permeability and increased bioavailability. Importantly, because of the higher resistance toward oxidative degradation, fluorinated compounds generally have higher metabolic stability. Therefore, development of new methods for C CF3 bond formation has caught great attention from the synthetic community during the past few years and different methods for the trifluoromethylation of arenes have been developed. Transition-metal-catalyzed and radical aromatic trifluoromethylation have been studied intensively (Scheme 1).

Enantioselective, desymmetrizing bromolactonization of alkynes.

Asymmetric bromolactonizations of alkynes are possible using a desymmetrization approach. The commercially available catalyst (DHQD)2PHAL promotes these cyclizations in combination with cheap NBS as a bromine source to give bromoenol lactones in high yield and with high enantioselectivity. The bromoenol lactone products, containing a tetrasubstituted alkene and a quaternary stereocenter, are valuable building blocks for synthetic chemistry.

Inclusion complexes of buckycatcher with C60 and C70

The dispersion corrected B97-D functional studies find a previously overlooked conformer of the buckycatcher C(60)H(28) (2) exhibiting intramolecular pi-pi stacking of its corannulene pincers to represent a global potential energy minimum conformation. B97-D/TZVP calculated geometry of C(60)@2 supramolecular assembly is in excellent agreement with the X-ray structure, slightly better than the previously reported M06-L results. In contrast, our calculated binding energy of C(60)@2 complex is dramatically higher than both M05-2X and M06-2X results and we conclude that the latter numbers are grossly underestimated. The lack of specificity of the buckycatcher for molecular recognition of C(60)vs. C(70) fullerenes is predicted by our calculations and confirmed by the NMR titration experiment which provides the equilibrium constant of 6800 +/- 400 M(-1) for association of C(70) with C(60)H(28) which is only slightly lower than the previously reported association constant of C(60)@2 assembly.

Silylium Ion-Catalyzed Challenging Diels–Alder Reactions: The Danger of Hidden Proton Catalysis with Strong Lewis Acids

The pronounced Lewis acidity of tricoordinate silicon cations brings about unusual reactivity in Lewis acid catalysis. The downside of catalysis with strong Lewis acids is, though, that these do have the potential to mediate the formation of protons by various mechanisms, and the thus released Brønsted acid might even outcompete the Lewis acid as the true catalyst. That is an often ignored point. One way of eliminating a hidden proton-catalyzed pathway is to add a proton scavenger. The low-temperature Diels-Alder reactions catalyzed by our ferrocene-stabilized silicon cation are such a case where the possibility of proton catalysis must be meticulously examined. Addition of the common hindered base 2,6-di-tert-butylpyridine resulted, however, in slow decomposition along with formation of the corresponding pyridinium ion. Quantitative deprotonation of the silicon cation was observed with more basic (Mes)(3)P to yield the phosphonium ion. A deuterium-labeling experiment verified that the proton is abstracted from the ferrocene backbone. A reasonable mechanism of the proton formation is proposed on the basis of quantum-chemical calculations. This is, admittedly, a particular case but suggests that the use of proton scavengers must be carefully scrutinized, as proton formation might be provoked rather than prevented. Proton-catalyzed Diels-Alder reactions are not well-documented in the literature, and a representative survey employing TfOH is included here. The outcome of these catalyses is compared with our silylium ion-catalyzed Diels-Alder reactions, thereby clearly corroborating that hidden Brønsted acid catalysis is not operating with our Lewis acid. Several simple-looking but challenging Diels-Alder reactions with exceptionally rare dienophile/enophile combinations are reported. Another indication is obtained from the chemoselectivity of the catalyses. The silylium ion-catalyzed Diels-Alder reaction is general with regard to the oxidation level of the α,β-unsaturated dienophile (carbonyl and carboxyl), whereas proton catalysis is limited to carbonyl compounds.

Stereoselective alcohol silylation by dehydrogenative Si-O coupling: scope, limitations, and mechanism of the cu-h-catalyzed non-enzymatic kinetic resolution with silicon-stereogenic silanes.

Ligand-stabilized copper(I)-hydride catalyzes the dehydrogenative Si-O coupling of alcohols and silanes-a process that was found to proceed without racemization at the silicon atom if asymmetrically substituted. The present investigation starts from this pivotal observation since silicon-stereogenic silanes are thereby suitable for the reagent-controlled kinetic resolution of racemic alcohols, in which asymmetry at the silicon atom enables discrimination of enantiomeric alcohols. In this full account, we summarize our efforts to systematically examine this unusual strategy of diastereoselective alcohol silylation. Ligand (sufficient reactivity with moderately electron-rich monophosphines), silane (reasonable diastereocontrol with cyclic silanes having a distinct substitution pattern) as well as substrate identification (chelating donor as a requirement) are introductorily described. With these basic data at hand, the substrate scope was defined employing enantiomerically enriched tert-butyl-substituted 1-silatetraline and highly reactive 1-silaindane. The synthetic part is complemented by the determination of the stereochemical course at the silicon atom in the Si-O coupling step followed by its quantum-chemical analysis thus providing a solid mechanistic picture of this remarkable transformation.

A unique transition metal-stabilized silicon cation.

Trivalent silicon cations are exceptionally strong electron pair acceptors that react, either desired or undesired, with almost any σ and π basic molecule. One way of intramolecular attenuation of the Lewis acidity of these superelectrophiles is by installation of a ferrocene unit at the electron-deficient silicon atom. While well-understood for isoelectronic α-ferrocenyl-substituted carbenium ions and also boranes, the stabilizing interactions between the ferrocene backbone and a positively charged silicon atom are not clear due to the challenge of crystallizing such cations. The structural characterization of our ferrocene-stabilized silicon cation now reveals an unprecedented bonding motif different from its analogues. An extreme dip angle of the silicon atom toward the iron atom is explained by two three-center-two-electron (3c2e) bonds through participation of both the upper and the lower aromatic rings of the ferrocene sandwich structure. The positive charge is still localized at the silicon atom that also retains a quasi-planar configuration.

Decarboxylative Polymerization of 2,6-Naphthalenedicarboxylic Acid at Surfaces

Metal-catalyzed polymerization of 2,6-naphthalenedicarboxylic acid (NDCA) to form poly-2,6-naphthalenes at various surfaces is reported. Polymerizations occur via initial formal dehydrogenation of self-assembled diacids with subsequent decarboxylation to give polymeric bisnaphthyl-Cu species at elevated temperature as intermediate structures (<160 °C). Further temperature increase eventually leads to poly-naphthalenes via reductive elimination. It is demonstrated that the Cu(111) surface works most efficiently to conduct such polymerizations as compared to the Au(111), Ag(111), Cu(100), and Cu(110) surfaces. Poly-2,6-naphthalene with a chain length of over 50 nm is obtained by using this approach. The decarboxylative coupling of aromatic diacids is a very promising tool which further enlarges the portfolio of reactions allowing for on-surface polymerizations and novel organometallic systems preparations.

Chiral Helical Oligotriazoles: New Class of Anion-Binding Catalysts for the Asymmetric Dearomatization of Electron-Deficient N-Heteroarenes

Helical chirality and selective anion-binding processes are key strategies used in nature to promote highly enantioselective chemical reactions. Although enormous efforts have been made to develop simple helical chiral systems and thus open new possibilities in asymmetric catalysis and synthesis, the efficient use of synthetic oligo- and polymeric helical chiral catalysts is still very challenging and rather unusual. In this work, structural unique chiral oligotriazoles have been developed as C-H bond-based anion-binding catalysts for the asymmetric dearomatization of N-heteroarenes. These rotational flexible catalysts adopt a reinforced chiral helical conformation upon binding to a chloride anion, allowing high levels of chirality transfer via a close chiral anion-pair complex with a preformed ionic substrate. This methodology offers a straightforward and potent entry to the synthesis of chiral (bioactive)heterocycles with added synthetic value from simple and abundant heteroarenes.

Formation of Isomeric BAr3 Adducts of 2‐Lithio‐N‐methylimidazole

N-Methylimidazole added to the strong organometallic Lewis acid B(C6F5)3 at the donor nitrogen atom to form the adduct 3 (characterized by X-ray diffraction). Deprotonation at the imidazole carbon atom C-2 was achieved by treatment with methyllithium to generate the reactive “Arduengo carbene anion” intermediate 4, which underwent a rapid subsequent intramolecular nucleophilic aromatic substitution reaction at one of the adjacent C6F5 groups to form the tricyclic betaine-type product 5. Rearrangement of 4 by 1,2-boron migration was not observed. The respective isomer 7 was prepared independently by deprotonation of N-methylimidazole, followed by C-2 addition of B(C6F5)3. The corresponding N-methylimidazolide-2−B(C6H5)3 adduct 8 was characterized by X-ray diffraction and shown to have a cyclodimeric structure made up of intermolecular bis(π-arene)(imidazole)lithium units. A DFT study revealed that the N-borated Arduengo carbene anions are in general very effectively kinetically protected from undergoing intramolecular rearrangement to their thermodynamically favored 2-boratoimidazole anion isomers by 1,2-BR3 migration. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Reversible Carbon Dioxide Binding by Simple Lewis Base Adducts with Electron-Rich Phosphines

For the efficient utilization of carbon dioxide as feedstock in chemical synthesis, low-energy-barrier CO2 activation is a valuable tool. We report a metal-free approach to reversible CO2 binding under mild conditions based on simple Lewis base adducts with electron-rich phosphines. Variable-temperature NMR studies and DFT calculations reveal almost thermoneutral CO2 binding with low-energy barriers or stable CO2 adduct formation depending on the phosphines donor ability. The most basic phosphine forms an air-stable CO2 adduct that was used as phosphine transfer agent, providing a convenient access to transition-metal complexes with highly electron-rich phosphine ligands relevant to catalysis.