Peter Kreitmeier

Application of Metal-Based Reagents and Catalysts in Microstructured Flow Devices

Over the years, organic synthesis has witnessed several improvements through the development of new chemical transformations or more efficient reagents for known processes. Likewise, technological advances, aiming at speeding up reactions and facilitating their work-up, have established themselves in academic as well as in industrial laboratories. In this Minireview, we highlight very recent developments in flow chemistry, focusing on organometallic reagents and catalysts. First, we describe reactions with homogeneous catalysts immobilized on different support materials using the concept of packed bed reactors. In the last chapter, we will discuss applications that utilize organometallic reagents.

Synthesis of a polyisobutylene-tagged fac-Ir(ppy)3 complex and its application as recyclable visible-light photocatalyst in a continuous flow process†

The facile synthesis and application of a polyisobutylene-polymer-tagged, iridium(III) photocatalyst is described. The catalytic performance of this complex remains consistently high, while the installed tether allows for its convenient separation from reaction products through a thermomorphic solvent system. Excellent recycling properties were observed both in batch and in flow reactions, and especially in the latter the continuous, automatic recovery and reuse of the catalyst either from a mono- or a biphasic reaction solution is realised, making this approach attractive for large-scale applications.

Visible light photoredox-catalyzed deoxygenation of alcohols

Summary Carbon–oxygen single bonds are ubiquitous in natural products whereas efficient methods for their reductive defunctionalization are rare. In this work an environmentally benign protocol for the activation of carbon–oxygen single bonds of alcohols towards a reductive bond cleavage under visible light photocatalysis was developed. Alcohols were activated as 3,5-bis(trifluoromethyl)-substituted benzoates and irradiation with blue light in the presence of [Ir(ppy)2(dtb-bpy)](PF6) as visible light photocatalyst and Hünig’s base as sacrificial electron donor in an acetonitrile/water mixture generally gave good to excellent yields of the desired defunctionalized compounds. Functional group tolerance is high but the protocol developed is limited to benzylic, α-carbonyl, and α-cyanoalcohols; with other alcohols a slow partial C–F bond reduction in the 3,5-bis(trifluoromethyl)benzoate moiety occurs.

Polyphospha[m]cyclo[n]carbons (m+n=15, 20, 25, 30, 40)

The Eglinton reaction of diethynyl(2,4,6-tri-tert-butylphenyl)phosphane (7 a), that is, the oxidative coupling of 3, 4, 5, or 6 of these phosphane units, affords a mixture of the 15-, 20-, 25-, and 30-membered macrocycles 8, 9, 10, and 11. Pure triphosphacyclopentadecahexayne 8 and pentaphosphacyclopentacosadecayne 10 were isolated by HPLC, while the mixture of 9 and 11 could not be separated. Multistep syntheses of open-chain polyphosphapolyynes are described, whose intra- or intermolecular coupling yields the phosphamacrocycles 8, 9, and 11. Eglinton coupling of bis(ethynylphosphanyl)butadiyne (17) gave a mixture of the 20-membered tetraphosphacycloicosaoctayne 9, the 30-membered hexaphosphacyclotriacontadodecayne 11, and the 40-membered octaphosphacyclotetracontahexadecayne 23 as result of a di-, tri-, and tetramerization, respectively. Intramolecular coupling of bis[(ethynylphosphanyl)butadiynyl]phosphane 25 a gave 8, while intermolecular coupling gave 11; these two compounds were isolated by chromatography to give yields of 70 and 5 %, respectively. The open-chain tetraphosphaeikosaoctayne 28 couples intramolecularly to give 9 and intermolecularly to give the 40-membered octaphosphacyclotetracontahexadecayne 23, which was isolated in the pure form. Octaphosphatetracontahexadecayne 32 cyclized to give 23, exclusively. The temperature-dependent 1H and 31P NMR spectra of the open-chain and cyclic ethynylphosphanes indicated a lowering of the inversion barrier of the tertiary phosphanes from the usual 130–140 kJ mol−1 to 65–75 kJ mol−1. Ab initio calculations proved that the dramatic reduction of the inversion barriers results from the interaction of the lone pair on phosphorus with the π orbitals of the triple bonds in the planar transition state during inversion. The situation is comparable with the dramatic reduction of the P inversion barrier in phospholes, because of the planar, aromatic transition state. The polyphospha[m]cyclo[n]carbons may be considered as precursors to cyclic PmCn systems.

Zur Moleküldynamik isomerer antiaromatischer [28]tetraoxaporphyrinogene (6.0.6.0) - isomere [26]tetraoxaporphyrin(6.0.6.0)dikationen

Abstract [24]Tetraoxaporphyrinogen(2.2.2.2) 1 as well as the [28]tetraoxaporphyrinogens 2 and 3 are highly dynamic molecules by rotation of the trans -ethene and the trans, trans -diene bridges around the σ-bonds, but the [24]tetraoxaporphyrinogen(4.0.4.0) 4 has no dynamic properties. We describe here the synthesis of the [28]tetraoxaporphyrinogen(6.0.6.0) 5 . Neither the isomer E,Z,E,E,Z,E- 5a nor Z,E,E,Z,E,E- 5b are (obviously due to the steric reasons) dynamic molecules. The porphyrinogens 5a as well as 5b are static molecules at any temperatures and as result of their geometry, which is close to planarity, they have clearly antiaromatic, paratropic character. Both isomers can be oxidized to give the corresponding aromatic, diatropic [26]tetraoxaporphyrin(6.0.6.0)dications 16a and 16b . Quantum mechanical calculations (AM1) are presented.

Enantioselective Synthesis of 4-Heterosubstituted Cyclopentenones

Racemic 4-hydroxycyclopentenone, readily derived from furfuryl alcohol, can be transformed via its O-Boc derivative to 4-acyloxy, 4-aryloxy-, 4-amino-, or 4-thio-substituted cyclopentenones with high enantioselectivity by palladium-catalyzed kinetic resolution via nucleophilic allylic substitutions. Applying this methodology, a short formal synthesis of ent-noraristeromycin was readily accomplished.

Konfigurations‐ und konformationsisomere paratrope, rotationsdynamische Tetraepoxy[32]annulene(6.2.6.2) und diatrope Tetraoxa[30]porphyrin(6.2.6.2)‐Dikationen : Nachweis eines Tetraepoxy[31]annulen(6.2.6.2)‐Radikalkations

Configurational and Conformational Isomeric Paratopic, Rotational Dynamics Tetraepoxy[30]annulenes(6.2.6.2) and Diatropic Tetraoxa[30]porphyrin(6.2.6.2) Dications: Detection of a Tetraepoxy[31]annulene(6.2.6.2)Radical Cation The synthesis of tetraepoxy[32]annulenes(6.2.6.2) (4) by a cyclizing twofold Wittig reaction of (E,E,E)-5,5′-(hexa-1,3,5-triene-1,6-diyl)bis[furan-2-carbaldehyde] (6) and the corresponding bis-phosphonium salt 7 is described (Scheme 1). Contrary to the configuration of the educts, the obtained annulenes 4a and 4b are (Z,E,E,E,Z,E,E,E)- and (E,Z,E,E,E,Z,E,E)-configurated, respectively. The 1H-NMR spectra establish the paratropic, antiaromatic character of 4. The annulenes 4 are highly dynamic systems, the (E)-ethenediyl bridges rotate around the adjacent σ-bonds, these rotations are frozen at −80°. The McMurry condensation of dialdehyde 6 yields the (E,E,Z,E,E,E,Z)-4,5-dihydrotetraepoxy[32]annulene(6.2.6.2) (13a), where the configuration of the dialdehyde 6 – beside the hydrogenated double bond – is retained. As result of an intramolecular McMurry reaction of 6, (Z,E,Z,Z)-dioxa[16]annulene(6.2) 14 is formed. By oxidation of the [32]annulenes(6.2.6.2) 4a and 4b, a mixture of the four stereoisomeric tetraoxa[30]porphyrin(6.2.6.2) dications 5a/5a′/5b/5c is obtained; the configuration of the isomers is determined by COSY, NOESY, and NOE experiments. The Δδ values (26.81, 25.83, and 21.11 ppm) underline the diatropic, aromatic character of the dications 5, the Soret bands are shifted bathochromically to 550 nm, and the Q-bands are in the NIR region (896 – 1039 nm). The dihydroannulene 13a is dehydrogenated by p-chloroanil (tetrachloro-1,4-benzoquinone) to give the annulenes 4a and 4b, its oxidation with DDQ (=4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile) results in the same mixture of dications 5. Entirely different results are obtained by reaction of the dihydroannulene 13a with DDQ. Here, the (E,E,E,Z,E,E,E,Z) tetraoxa[30]porphyrin(6.2.6.2) dication 5c – formed only in traces from 4a/4b – is the main product. Beside 5c, a by-product (3%) can be isolated, which turns out (ESR, conductivity) to be the (E,E,E,Z,E,E,E,Z)-tetraoxa[31]porphyrin(6.2.6.2) radical cation 16, obviously the intermediate in the oxidation sequence of the annulene to the dication. This result leads to the conclusion that the reaction of the dihydro compound 13a with p-chloroanil and DDQ follows different reaction mechanisms. For all isolated stereoisomeric tetraepoxy annulenes and tetraoxaporphyrin dications, the ΔHf values are calculated by the semiempiric AM1 method. The results are in agreement with the experimental observations. All data confirm the antiaromaticity of the tetraepoxy[32]annulenes(6.2.6.2) 4 and the aromaticity of the tetraoxa[30]porphyrin(6.2.6.2) dications.

Visible‐Light‐Promoted Generation of α‐Ketoradicals from Vinyl‐bromides and Molecular Oxygen: Synthesis of Indenones and Dihydroindeno[1,2‐c]chromenes

Ortho-alkynylated α-bromocinnamates can be converted by a visible-light-mediated photocascade reaction with molecular oxygen into either indenones or dihydroindeno[1,2-c]chromenes. The one-step process features key photochemical steps, that is, the initial activation of vinyl bromides through energy transfer to give α-ketoradicals in a reaction with molecular oxygen, followed by α-oxidation of an arene moiety by 6-π electrocyclization, and subsequent hydroxylation by an electron-transfer process from the same photocatalyst leads to the dihydroindeno[1,2-c]chromenes.

Cytotoxic steroidal saponins from the rhizomes of Tacca integrifolia

Three new steroid saponins (3β,25R)‐spirost‐5‐en‐3‐yl 6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[β‐D‐glucopyranosyl‐(1→4)‐6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (1), (3β,22R,25R)‐26‐(β‐D‐glucopyranosyloxy)‐22‐hydroxyfurost‐5‐en‐3‐yl 6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (3), and (3β,22R,25R)‐26‐(β‐D‐glucopyranosyloxy)‐22‐hydroxyfurost‐5‐en‐3‐yl 6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[β‐D‐glucopyranosyl‐(1→4)‐6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (5), as well as the new pregnane glycoside (3β,16β)‐3‐{[6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranosyl]oxy}‐20‐oxopregn‐5‐en‐16‐yl (4R)‐5‐(β‐D‐glucopyranosyloxy)‐4‐methylpentanoate (6), were isolated from the rhizomes of Tacca integrifolia together with two known (25R) configurated steroid saponins (3β,25R)‐spirost‐5‐en‐3‐yl 6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (2) and (3β,22R,25R)‐26‐(β‐D‐glucopyranosyloxy)‐22‐methoxyfurost‐5‐en‐3‐yl 6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (4). The cytotoxic activity of the isolated compounds was evaluated in HeLa cells and showed the highest cytotoxicity value for compound 2 with an IC50 of 1.2±0.4 μM. Intriguingly, while compounds 1–5 exhibited similar cytotoxic properties between 1.2±0.4 (2) and 4.0±0.6 μM (5), only compound 2 showed a significant microtubule‐stabilizing activity in vitro.

Reversible magnetic mercury extraction from water

A facile and efficient way to decontaminate mercury(II) polluted water with the aid of magnetic, highly stable and recyclable carbon coated cobalt (Co/C) nanoparticles is reported. Comparing non-functionalised Co/C nanomagnets with particles that were functionalised with amino moieties, the latter one proved to be more effective for scavenging mercury with respect to extraction capacity and recyclability. A novel nanoparticle–poly(ethyleneimine) hybrid (Co/C–PEI) prepared by direct ring opening polymerization of aziridine initiated by an amine functionalised nanoparticle surface led to a high capacity material (10 mmol amino groups per g nanomaterial) and thus proved to be the best material for scavenging toxic mercury at relevant concentrations (mg L−1/μg L−1) for at least 6 consecutive cycles. On a large-scale, 20 L of drinking water with an initial Hg2+ concentration of 30 μg L−1 can be decontaminated to the level acceptable for drinking water (≤2 μg L−1) with just 60 mg of Co/C–PEI particles.