Archive

New Publication in Journal of the American Chemical Society

Enantioselective Redox-Neutral Rh-Catalyzed Coupling of Terminal Alkynes with Carboxylic Acids Toward Branched Allylic Esters

We report on the first enantioselective variant of the atom-economic and redox-neutral coupling of carboxylic acids with terminal alkynes under rhodium catalysis utilizing the chiral, bidentate (R,R)-Cp-DIOP ligand. This represents the first example of this convenient asymmetric access to valuable branched allylic esters. The utility of this methodology is demonstrated by both a reaction performed on large scale and a short three-step synthesis of two naturally occurring γ-butyrolactones. A stereochemical model explaining the observed absolute configuration of the products based on DFT calculations is given.

P. Koschker, M. Kähny, B. Breit, J. Am. Chem. Soc., 2015, 137 (8), 3131–3137; (link)

35th Regiosymposium 2015

New Publication in Angewandte Chemie

Asymmetric Rhodium-Catalyzed Addition of Thiols to Allenes: Synthesis of Branched Allylic Thioethers and Sulfones

All about S: The rhodium-catalyzed enantioselective hydrothiolation of terminal monosubstituted allenes with aromatic and functionalized aliphatic thiols permits the atom-economic synthesis of valuable branched allylic thioethers and sulfones in high regio- and enantioselectivity. By varying the ligand and reaction conditions both aromatic and aliphatic thiols were tolerated.

New Publication in Angewandte Chemie

Rhodium-Catalyzed Chemo-, Regio-, and Enantioselective Addition of 2-Pyridones to Terminal Allenes

A rhodium-catalyzed chemo-, regio-, and enantioselective addition of 2-pyridones to terminal allenes to give branched N-allyl 2-pyridones is reported. Preliminary mechanistic studies support the hypothesis that the reaction is initiated from the more acidic 2-hydroxypyridine form, and the initial kinetic O-allylation product was finally converted into the thermodynamically more stable N-allyl 2-pyridone.

New VIP-Publication in Angewandte Chemie

Unlocking the N² Selectivity of Benzotriazoles: Regiodivergent and Highly Selective Coupling of Benzotriazoles with Allenes

Ligand control: Exceptionally high N² and N¹ selectivities have been achieved in the rhodium-catalyzed coupling of benzotriazoles with allenes by using DPEphos and JoSPOphos, respectively (see scheme). This method permits the atom-economic synthesis of valuable branched N²- and N¹-allylated benzotriazole derivatives.

New Publication in Angewandte Chemie

Atom-Economic, Regiodivergent, and Stereoselective Coupling of Imidazole Derivatives with Terminal Allenes

Taking control:New Rh- and Pd-catalyzed regiodivergent and stereoselective intermolecular coupling reactions of imidazole derivatives with monosubstituted allenes are reported. Using a Rh^I/Josiphos system, perfect regioselectivities and high enantiomeric excess were obtained, while a Pd^II/dppf system gave the linear products with high regioselectivities and high E/Z selectivities. dppf=1,1′-bis(diphenylphosphino)ferrocene, Josiphos=(R)-1-[(Sp)-2-(dicyclohexylphosphino)ferrocenyl]ethyldialkylphosphine.

New Publications in Journal of the American Chemical Society

(1) Rhodium-Catalyzed Chemo- and Regioselective Decarboxylative Addition of β-Ketoacids to Allenes: Efficient Construction of Tertiary and Quaternary Carbon Centers

A rhodium-catalyzed chemo- and regioselective intermolecular decarboxylative addition of β-ketoacids to terminal allenes is reported. Using a Rh(I)/DPPF system, tertiary and quaternary carbon centers were formed with exclusively branched selectivity under mild conditions. Preliminary mechanism studies support that the carbon–carbon bond formation precedes the decarboxylation and the reaction occurs in an outer-sphere mechanism.

C. Li, B. Breit, J. Am. Chem. Soc., 2014, 136 (3), 862–865; (link)

(2) Mechanistic Investigations of the Rhodium Catalyzed Propargylic CH Activation

Previously we reported the redox-neutral atom economic rhodium catalyzed coupling of terminal alkynes with carboxylic acids using the DPEphos ligand. We herein present a thorough mechanistic investigation applying various spectroscopic and spectrometric methods (NMR, in situ-IR, ESI-MS) in combination with DFT calculations. Our findings show that in contrast to the originally proposed mechanism, the catalytic cycle involves an intramolecular protonation and not an oxidative insertion of rhodium in the OH bond of the carboxylic acid. A σ-allyl complex was identified as the resting state of the catalytic transformation and characterized by X-ray crystallographic analysis. By means of ESI-MS investigations we were able to detect a reactive intermediate of the catalytic cycle.

U. Gellrich, A. Meißner, A. Steffani, M. Kähny, H.-J. Drexler, D. Heller, D. A. Plattner, B. Breit, J. Am. Chem. Soc., 2014, 136 (3), 1097–1104; (link)

New Publication in Chemistry - A European Journal

Realistic Energy Surfaces for Real-World Systems: An IMOMO CCSD(T):DFT Scheme for Rhodium-Catalyzed Hydroformylation with the 6-DPPon Ligand

A two-layer model (CCSD(T):DFT) in the framework of an integrated molecular orbital plus molecular orbital (IMOMO) scheme (see figure) was evaluated for rhodium-catalyzed hydroformylation with the self-assembling 6-diphenylphosphinopyridine-(2H)-1-one ligand (6-DPPon). By applying the energetic-span model, an excellent match between the calculated and experimentally observed turnover frequencies was achieved.

U. Gellrich, D. Himmel, M. Meuwly, B. Breit, Chem. Eur. J. 2013, 19, 16272-16281; (link)

New Publications in Angewandte Chemie

(1) Catalytic Asymmetric Synthesis of Allylic Alcohols and Derivatives and their Applications in Organic Synthesis

 Allylic alcohols represent an important and highly versatile class of chiral building blocks for organic synthesis. This Review summarizes the plethora of methods developed for the catalytic asymmetric synthesis of enantioenriched allylic alcohols. These include: dynamic kinetic resolution (DKR/DKAT), nucleophilic 1,2-addition to carbonyl groups, allylic substitution, oxidation of C[BOND]H bonds, the addition of O nucleophiles to π systems, reduction of unsaturated carbonyl compounds, and an alternative route from enantioenriched propargylic alcohols. Furthermore, these catalytic asymmetric processes are exemplified by their applications in the syntheses of complex molecules such as natural products and potential therapeutic agents.

M. A. Lumbroso, M. L. Cooke, B. Breit, Angew. Chem. 2013, 125, 1942–1986; (link) Angew. Chem. Int. Ed. 2012, 51, 1890–1932. (link)

(2) Catalytic Hydrogenation of Amides to Amines under Mild Conditions

Under (not so much) pressure : A general method for the hydrogenation of tertiary and secondary amides to amines with excellent selectivity using a bimetallic Pd–Re catalyst has been developed. The reaction proceeds under low pressure and comparatively low temperature. This method provides organic chemists with a simple and reliable tool for the synthesis of amines.

U. M. Stein, B. Breit, Angew. Chem. 2013, 125, 2287-2290; (link) Angew. Chem. Int. Ed. 2013, 52, 2231-2234. (link)

New Publications in Angewandte Chemie

(1) Enantioselective Rhodium-Catalyzed Synthesis of Branched Allylic Amines by Intermolecular Hydroamination of Terminal Allenes

 Branching out: The rhodium-catalyzed enantioselective hydroamination of monosubstituted allenes with anilines permits the atom-economic synthesis of valuable branched allylic amines. In contrast to previous linear selective allene hydroaminations, a Rh^I/Josiphos catalyst system (see scheme; cod=1,5-cyclooctadiene, DCE=1,2-dichloroethane) allows branched allylic amines to be obtained with perfect regioselectivity, high yield, and good enantioselectivity.

M. L. Cooke, Kun Xu, B. Breit, Angew. Chem. 2012, 124, 11034-11037; (link) Angew. Chem. Int. Ed. 2012, 51, 10876-10879. (link)

(2) Mechanistic Insights into a Supramolecular Self-Assembling Catalyst System: Evidence for Hydrogen-Bonding during Rhodium-Catalyzed Hydroformylation

The structural integrity and flexibility provided by intermolecular hydrogen bonds leads to the outstanding properties of the 6-diphenylphosphinopyridin-(2H)-1-one ligand (see scheme) in the rhodium-catalyzed hydroformylation of terminal alkenes, as demonstrated by the combination of spectroscopic methods and DFT computations. Hydrogen bonds were also detected in a competent intermediate of the catalytic cycle.

U. Gellrich, W. Seiche, M. Keller, B. Breit, Angew. Chem. 2012, 124, 11195-11200; (link) Angew. Chem. Int. Ed. 2012, 51, 11033-11038. (link)

(3) Preparation of Alkylmagnesium Reagents from Alkenes through Hydroboration and Boron-Magnesium Exchange

Tolerant: Alkylmagnesium reagents can be synthesized from alkenes through a sequence of hydroboration and subsequent boron–magnesium exchange using a method that tolerates different functional groups (see scheme). The resulting alkylmagnesium reagents can be used in carbon–carbon bond forming reactions, such as alkylation reactions or transition-metal-catalyzed cross-coupling reactions.

M. Reichle, B. Breit, Angew. Chem. 2012, 124, 5828-5832; (link) Angew. Chem. Int. Ed. 2012, 51, 5730-5734. (link) highlighted in SynFacts as Synfact of the Month September (link)

(4) Tandem Rhodium-Catalyzed Hydroformylation-Hydrogenation of Alkenes by Employing a Cooperative Ligand System

Dual action: A multifunctional rhodium catalyst system enables the simultaneous catalysis of two distinct transformations, hydroformylation of an alkene and reduction of an aldehyde, in a highly selective manner. This one-pot/two-step process is controlled by the cooperative action of two different supramolecular ligand systems and transforms terminal alkenes into C₁-chain-elongated linear

D. Fuchs, G. Rousseau, L. Diab, U. Gellrich, B. Breit, Angew. Chem. 2012, 124, 2220-2224; (link) Angew. Chem. Int. Ed. 2012, 51, 2178-2182. (link)

2 PostDoc Positions available

Postdoctoral Position (E13) available for a collaboration project with Syngenta Crop Science
The candidate  will have to develop selective hydroformylation reactions of specifically functionalized alkenes as a key step for heterocycle synthesis. Experience in organic synthesis and/or transition metal catalysis and/or carbonylation chemistry is of advantage. Please send your application including two letters of recommendation to bernhard.breit@chemie.uni-freiburg.de

In the framework of SFB 992 Medical Epigenetics (MEDEP): From basic mechanisms to clinical applications we offer one PostDoc postion (E13) in Synthetic Organic Chemistry

Topic: Synthesis of potent and selective small molecules that regulate epigenetic pathways and can be utilised as chemical probes for cellular and animal studies.

Excellent candidates, please contact Prof. Dr. B. Breit (bernhard.breit@chemie.uni-freiburg.de) directly.

Übung Vorlesung Reaktionmechanismen

Inhalt der Übungen: Besprechung des mechanistischen Verlaufs der einzelnen Präparate

Beginn: Mo, 30.04.12, 9-10 Uhr, SR123/124

Übung 1: Radikalische Substitution am gesättigten C-Atom, Präparate 1-1 bis 1-8

(Gesamt)-Nachklausur OCI, 04.04.2012

9-12 Uhr HS Chemie

OGP-LA 2012 (WPO2001)

Anmeldefrist bis: 31.01.2012, Aushang

Open House - Vorstellung der B.Sc.-Themen

Wann: Mittwoch, 18.01.12, 18.15 Uhr

Wo: SR704

Was: Vorstellung möglicher B.Sc.-Themen bei Brezeln und Bier

Ergebnis Wiederholungsklausur Teil A zur Vorlesung Organische Experimentalchemie I vom 04.01.2012

Ergebnisliste: Erdgeschoß Chemiehochhaus,  "Schwarzes Brett" vor den Aufzügen

Einsicht: Donnerstag, 05.01.2012, 14.00 Uhr, SR704 oder im Sekretariat von Herrn Prof. Breit

Ergebnis Klausur Teil A zur Vorlesung Organische Experimentalchemie I vom 17.12.2011

Ergebnisliste: Erdgeschoß Chemiehochhaus,  "Schwarzes Brett" vor den Aufzügen

Einsicht: Dienstag, 20.12.2011, 13.00-14.00 Uhr, SR44/45

New Publication in JACS

Enantioselective Synthesis of Branched Allylic Esters via Rhodium-Catalyzed Coupling of Allenes with Carboxylic Acids

We report on the first intermolecular asymmetric catalytic regio- and enantioselective addition of carboxylic acids to terminal allenes to form valuable branched allylic esters, employing a rhodium(I)/(R,R)-DIOP catalyst system.

P. Koschker, A. Lumbroso, B. Breit* J. Am. Chem. Soc. 2011, ASAP, DOI: 10.1021/ja210149g

New Angewandte Hot Paper

Divergent Regioselectivity in the Synthesis of Trisubstituted Allylic Alcohols by Nickel- and Ruthenium-Catalyzed Alkyne Hydrohydroxymethylation with Formaldehyde

Stoichiometric metals banned: Nonsymmetrically disubstituted alkynes were converted into primary trisubstituted allylic alcohols upon exposure to paraformaldehyde in the presence of nickel or ruthenium catalysts, which exhibit complementary regioselectivity and complete stereoselectivity in the absence of exogenous reducing agents (see scheme).

C. C. Bausch, R. L. Patman, B. Breit*, M. J. Krische* Angew. Chem. 2011, 123(25), 5805-5808

DOI: 10.1002/anie.201101496

New Publication in JACS

Redox-Neutral Atom-Economic Rhodium-Catalyzed Coupling of Terminal Alkynes with Carboxylic Acids Toward Branched Allylic Esters

Alexandre Lumbroso, Philipp Koschker, Nicolas R. Vautravers and Bernhard Breit JACS 2011, 133, 2386-2389, pdf

 Bachelor- und Mitarbeiterprojekte

            

Zu finden:

Chemiehochhaus 2. OG vor dem OFP-Saal