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New Publication in Nature Communications
Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines
The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue.
K. Xu, T. Gilles, B. Breit, Nat. Commun., 2015, 6, 7616; (link)
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.A. B. Pritzius, B. Breit, Angew. Chem. 2015, 127, 3164-3168; (link) Angew. Chem. Int. Ed. 2015, 54, 3121-3125. (link)
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.C. Li, M. Kähny, B. Breit, Angew. Chem. 2014, 126, 14000-14004; (link) Angew. Chem. Int. Ed. 2014, 53, 13780-13784. (link )
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.K. Xu, N. Thieme, B. Breit, Angew. Chem. 2014, 126, 7396-7399; (link) Angew. Chem. Int. Ed. 2014, 53, 7268-7271. (link)
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 RhI/Josiphos system, perfect regioselectivities and high enantiomeric excess were obtained, while a PdII/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.K. Xu, N. Thieme, B. Breit, Angew. Chem. 2014, 126, 2194-2197; (link) Angew. Chem. Int. Ed. 2014, 53, 2162-2165. (link)
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.
(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.