Lehrstuhl für
Organische Chemie I
Lichtenbergstraße 4
85747 Garching

Tel  +89.289.13330
Fax +89.289.13315

 
Aktuelle Publikationen
Catalytic deracemization of chiral allenes by sensitized excitation with visible light
Nature 2018, 564, 240-243
Enantioselective Lewis Acid Catalyzed ortho Photocycloaddition of Olefins to Phenanthrene-9-carboxaldehydes
Angew. Chem. Int. Ed. 2018, 57, 14593-14596
Chromophore Activation of α,β-Unsaturated Carbonyl Compounds and Its Application to Enantioselective Photochemical Reactions
Angew. Chem. Int. Ed. 2018, 57, 14338-14349
Enantioselective Intermolecular [2+2] Photocycloaddition Reaction of Cyclic Enones and Its Application in a Synthesis of (–)-Grandisol
J. Am. Chem. Soc. 2018, 140, 3228-3231

Research

The major goals of our research are the development and application of new synthetic methods in organic chemistry. The focus is on catalytic methods, which enable previously unknown transformations employing both photochemical and conventional techniques. Our research is curiosity-driven and does not strive for immediate industrial application. However, entrepreneurial opportunities will be considered where applicable.

Natural product synthesis

The selection of natural product targets in our group is based on aspects of structural uniqueness, suitable new methodology and biological activity. In our work we have been able to prove the constitution and configuration of several natural products by accomplishing their first total syntheses. Examples include the syntheses of wailupemycin B, punctaporonin C, lactiflorin, and pinolinone.

Wailupemycin B
ACIE 2003, 42, 4685-4687
Wailupemycin B
Punctaporonin C
ACIE 2008, 47, 6189-6191
Punctaporonin C
Lactiflorin
ACIE 2012, 51, 1261-1264
Lactiflorin
Pinolinone
CC 2014, 50, 3353-3355
Pinolinone

New synthetic methods, which were developed in our group have been successfully applied to the synthesis of natural products. The synthesis of meloscine for example was the first synthesis, employing an enantioselective photochemical key step in natural product synthesis. A C-H activation protocol, which we developed for addressing the C2 position of the indole core, was applied to the synthesis of the aspidosperma alkaloids aspidospermidine and goniomitine. Our interest in diastereoselective reactions of carbenium ions led to a concise synthesis of podophyllotoxin.

Meloscine
ACIE 2008, 47, 5082-5084
Meloscine
Aspidospermidine and Goniomitine
JACS 2012, 134, 14563-14572
Aspidospermidine and Goniomitine
Podophyllotoxin
ACIE 2008, 47, 7557-7559
Podophyllotoxin

Biological activity is a further motivation to approach a synthetic target. In this regard, our research has been devoted to the synthesis of anticancer and antiinfective compounds. Exemplarily, the syntheses of the GE-factors and the amythiamicins are mentioned here, which address the bacterial elongation factor EF-Tu.

GE2270
ACIE 2007, 46, 4771-4774; CEJ 2010, 16, 14083-14093
GE2270
Amythiamicin C
CEJ 2010, 16, 14083–14093; CMC 2013, 8, 1954-1962
Amythiamicin C

Catalytic Methods

Our interest in the synthesis of heterocycles has led to the development of regioselective cross-coupling reactions, which in turn have found widespread applications. In recent years, interest has shifted towards the direct C-C bond formation on heterocyclic cores by C-H activation reactions. Examples include the alkylation of indoles and pyrroles and the arylation of thiophenes.

JACS 2011, 133, 12990-12993
Direct C-C bond formation by C-H activation

The facial diastereoselectivity in the intermolecular reaction of free carbenium ions was first addressed by our group. It was shown that the reaction of benyzlic cations proceed with high diastereoselectivity and that the outcome depends on the steric size of the respective substituents at the stereogenic center in α-position of the cation. Catalytic versions of these transformations were developed employing FeCl3, AuCl3 or Bi(OTf)3 as catalysts. The study has been further extended to allyllic and propargylic cations.

JACS 2006, 128, 9668-9675; CAJ 2008, 3, 272-284; JACS 2014, 136, 2851-2857
Diastereoselective C-C bond formation in free carbenium ion reactions

Initial work in the area of supramolecular catalysis was dedicated towards finding enantioselective catalysts for photochemical reactions (see below). Our interest in this topic has further expanded towards enantio- and regioselective transition metal catalysis. Therefore, we designed templates, which bear a site for substrate binding via hydrogen bonds and which also enable the attachment of catalytically active transition metals, such as Mn, Ru or Rh. Proof of principle studies were performed using a Ru-based oxidation catalyst and quinolone-based olefins for selective epoxidation reactions. It was unambiguously proven that hydrogen bonding is responsible for both regio- and enantioselectivity. Rh catalysis allowed us to address the issue of enantioselective amination and aziridination.

CC 2011, 47, 2137-2139
Mn-salen complex with two hydrogen-bonding-sites for enantioselective catalysis
JACS 2010, 132, 15911-15913; ACIE, in press
Ru-porphyrin complex with a hydrogen-bonding-site for enantioselective catalysis

CC 2013, 49, 8009-8011; CEJ 2014, 20, 13522-13526
Rh-esp complex with two hydrogen-bonding-sites for enantioselective catalysis

Photochemistry

Based on the 1,5,7-trimethyl-3-azabicyclo[3.3.1]nonane-2-one scaffold, which is readily derived from Kemp's triacid, we have developed a chiral template for photochemical and radical reactions, which has proven its versatility over the last ten years. Interestingly, the template showed some enantioselective catalytic activity in radical reactions.

OL 2006, 8, 3145-3147; ACIE 2004, 43, 5849-5851
Hydrogen-bond-mediated enantioselective radical cyclisation

In recent years, it has been successfully employed for enantioselective intra- and intermolecular [2+2] photocycloaddition reactions of isoquinolones.

JACS 2013, 135, 14948-14951; ACIE 2011, 50, 8416-8419
Mn-salen complex with two hydrogen-bonding-sites for enantioselective catalysis

Upon modification of the oxazole backbone, it was possible to develop the template into enantioselective photocatalysts, which work either by electron transfer or by energy transfer. A ketone served as catalyst in the enantioselective photoredox cyclization of an aminoethyl quinolone.

Nature 2005, 436, 1139-1140
Catalytic enantioselective PET-initiated alpha-aminoradical-cyclization

Xanthones and thioxanthones can be employed for the enantioselective sensitization of [2+2] photocycloaddition reactions at catalyst loadings as low as 2.5 mol%. Thioxanthone sensitization can be performed very efficiently with artificial visible light sources or with sunlight.

ACIE 2014, 53, 7661-7664; JACS 2011, 133, 16689-16697; ACIE 2009, 48, 6640-6642
Catalytic enantioselective sensitization of a [2+2] photocycloaddition

Lewis acid catalysis was identified as a method to achieve enantioselective photochemical reactions in 2010 as demonstrated for the intramolecular [2+2] photocycloaddition of coumarins. In 2013, it was shown that enantioselective Lewis acid catalysis is not restricted to the coumarin [2+2] photocycloaddition but can - unexpectedly - also be applied to enone [2+2] photocycloaddition reactions. The outcome is unexpected because enones - unlike coumarins - undergo uncatalyzed [2+2] photocycloaddition reactions at λ = 366 nm. The mode of action in the enone case is clearly different from the coumarin case. Enantioselective Lewis acid catalysis of enone [2+2] photocycloaddition seems to be relatively general and was applied not only to dihydropyridones but more recently also to 2-cyclohexenone substrates.

ACIE 2010, 49, 7782-7785
Lewis-acid catalyzed enantioselective [2+2] photocycloaddition of coumarines
Science 2013, 342, 840-843
Lewis-acid catalyzed enantioselective [2+2] photocycloaddition of piperidones

ACIE 2014, 53, 12921-12924
Lewis-acid catalyzed enantioselective [2+2] photocycloaddition of cyclohexenones

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