86703-56-2Relevant academic research and scientific papers
Uncovering Key Structural Features of an Enantioselective Peptide-Catalyzed Acylation Utilizing Advanced NMR Techniques
Procházková, Eli?ka,Kolmer, Andreas,Ilgen, Julian,Schwab, Mira,Kaltschnee, Lukas,Fredersdorf, Maic,Schmidts, Volker,Wende, Raffael C.,Schreiner, Peter R.,Thiele, Christina M.
, p. 15754 - 15759 (2016/12/16)
We report on a detailed NMR spectroscopic study of the catalyst-substrate interaction of a highly enantioselective oligopeptide catalyst that is used for the kinetic resolution of trans-cycloalkane-1,2-diols via monoacylation. The extraordinary selectivity has been rationalized by molecular dynamics as well as density functional theory (DFT) computations. Herein we describe the conformational analysis of the organocatalyst studied by a combination of nuclear Overhauser effect (NOE) and residual dipolar coupling (RDC)-based methods that resulted in an ensemble of four final conformers. To corroborate the proposed mechanism, we also investigated the catalyst in mixtures with both trans-cyclohexane-1,2-diol enantiomers separately, using advanced NMR methods such as T1relaxation time and diffusion-ordered spectroscopy (DOSY) measurements to probe molecular aggregation. We determined intramolecular distance changes within the catalyst after diol addition from quantitative NOE data. Finally, we developed a pure shift EASY ROESY experiment using PSYCHE homodecoupling to directly observe intermolecular NOE contacts between the trans-1,2-diol and the cyclohexyl moiety of the catalyst hidden by spectral overlap in conventional spectra. All experimental NMR data support the results proposed by earlier computations including the proposed key role of dispersion interaction.
A photoinduced cyclization cascade - Total synthesis of (-)-leuconoxine
Pfaffenbach, Magnus,Gaich, Tanja
, p. 6355 - 6357 (2015/04/22)
A protecting-group-free and enantioselective total synthesis of the monoterpenoid indole alkaloid (-)-leuconoxine was accomplished. The key step comprises a novel photoinduced domino macrocyclization/transannular cyclization involving the Witkop cyclization, for which additional mechanistic evidence is provided. This process furnishes a diaza[5.5.6.6]fenestrane skeleton, which is a hitherto unprecedented structure element.
Alcohol cross-coupling for the kinetic resolution of diols via oxidative esterification
Hofmann, Christine,Schümann, Jan M.,Schreiner, Peter R.
, p. 1972 - 1978 (2015/02/19)
We present an organocatalytic C-O-bond cross-coupling strategy to kinetically resolve racemic diols with aromatic and aliphatic alcohols, yielding enantioenriched esters. This one-pot protocol utilizes an oligopeptide multicatalyst, m-CPBA as the oxidant, and N,N-diisopropylcarbodiimide as the activating agent. Racemic acyclic diols as well as trans-cycloalkane-1,2-diols were kinetically resolved, achieving high selectivities and good yields for the products and recovered diols.
Functionality, Effectiveness, and Mechanistic Evaluation of a Multicatalyst-Promoted Reaction Sequence by Electrospray Ionization Mass Spectrometry
Alachraf, M. Wasim,Wende, Raffael C.,Schuler, S?ren M. M.,Schreiner, Peter R.,Schrader, Wolfgang
, p. 16203 - 16208 (2015/11/03)
A multicatalytic three-step reaction consisting of epoxidation, hydrolysis, and enantioselective monoacylation of cyclohexene was studied by using mass spectrometry (MS). The reaction sequence was carried out in a one-pot reaction using a multicatalyst. All reaction steps were thoroughly analyzed by electrospray ionization (ESI) MS (and MS/MS), as well as high-resolution MS for structure elucidation. These studies allow us to shed light on the individual mode of action of each catalytic moiety. Thus, we find that under the epoxidation conditions, the catalytically active N-methyl imidazole for the terminal acylation step is partially deactivated through oxidation. This observation helps to explain the lower efficiency of the catalyst in the last step compared to the monoacylation performed separately. All reactive intermediates and products of the reaction sequence, as well as of the side-reactions, were monitored, and we present a working mechanism of the reaction.
Organocatalytic asymmetric hydrolysis of epoxides
Monaco, Mattia Riccardo,Prevost, Sebastien,List, Benjamin
, p. 8142 - 8145 (2014/08/18)
The hydrolytic ring opening of epoxides is an important biosynthetic transformation and is also applied industrially. We report the first organocatalytic variant of this reaction, exploiting our recently discovered activation of carboxylic acids with chiral phosphoric acids via heterodimerization. The methodology mimics the enzymatic mechanism, which involves an enzyme-bound carboxylate nucleophile. A newly designed phosphoric acid catalyst displays high stereocontrol in the desymmetrization of meso-epoxides. The methodology shows wide generality with cyclic, acylic, aromatic, and aliphatic substrates. We also apply our method in the first highly enantioselective anti-dihydroxylation of simple olefins.
Highly enantioselective organocatalytic oxidative kinetic resolution of secondary alcohols using chiral alkoxyamines as precatalysts: Catalyst structure, active species, and substrate scope
Murakami, Keiichi,Sasano, Yusuke,Tomizawa, Masaki,Shibuya, Masatoshi,Kwon, Eunsang,Iwabuchi, Yoshiharu
supporting information, p. 17591 - 17600 (2015/02/19)
The development and characterization of enantioselective organocatalytic oxidative kinetic resolution (OKR) of racemic secondary alcohols using chiral alkoxyamines as precatalysts are described. A number of chiral alkoxyamines have been synthesized, and their structure-enantioselectivity correlation study in OKR has led us to identify a promising precatalyst, namely, 7-benzyl-3-n-butyl-4-oxa-5-azahomoadamantane, which affords various chiral aliphatic secondary alcohols (ee up to >99%, krel up to 296). In a mechanistic study, chlorine-containing oxoammonium species were identified as the active species generated in situ from the alkoxyamine precatalyst, and it was revealed that the chlorine atom is crucial for high reactivity and enantioselectivity. The present OKR is the first successful example applicable to various unactivated aliphatic secondary alcohols, including heterocyclic alcohols with high enantioselectivity, the synthetic application of which is demonstrated by the synthesis of a bioactive compound.
Lipophilic oligopeptides for chemo- and enantioselective acyl transfer reactions onto alcohols
Mueller, Christian E.,Zell, Daniela,Hrdina, Radim,Wende, Raffael C.,Wanka, Lukas,Schuler, Soeren M. M.,Schreiner, Peter R.
, p. 8465 - 8484 (2013/09/24)
Inspired by the extraordinary selectivities of acylases, we envisioned the use of lipophilic oligopeptidic organocatalysts for the acylative kinetic resolution/desymmetrization of rac- and meso-cycloalkane-1,2-diols. Here we describe in a full account the discovery and development process from the theoretical concept to the final catalyst, including scope and limitations. Competition experiments with various alcohols and electrophiles show the full potential of the employed oligopeptides. Additionally, we utilized NMR and IR-spectroscopic methods as well as computations to shed light on the factors responsible for the selectivity. The catalyst system can be readily modified to a multicatalyst by adding other catalytically active amino acids to the peptide backbone, enabling the stereoselective one-pot synthesis of complex molecules from simple starting materials.
Stereochemical study on an oxygen-directed olefin oxidation and subsequent oxygen cyclization: Differences between peracid and metal oxide-catalyzed hydroperoxide in oxidation reactions
Inoue, Aya,Misaki, Tomonori,Fujita, Morifumi,Okuyama, Tadashi,Sugimura, Takashi
, p. 833 - 837 (2013/08/23)
Optically active (2S,4R)-2-hydroxy-4-pentyl enol ether was prepared for the first time and subjected to hydroxy-directed oxidations at the olefinic group. Treatment with m-chloroperbenzoic acid and tert-butyl hydroperoxide/vanadium acetylacetonate resulte
Enantiomerically enriched trans-diols from alkenes in one pot: A multicatalyst approach
Hrdina, Radim,Mueller, Christian E.,Wende, Raffael C.,Wanka, Lukas,Schreiner, Peter R.
supporting information; experimental part, p. 2498 - 2500 (2012/04/10)
Multicatalysts consisting of non-natural oligopeptides with distinctly different catalytic moieties create molecular complexity in a multistep one-pot sequence starting from simple alkenes yielding highly enantiomerically enriched trans-diols. The Royal Society of Chemistry 2012.
A multicatalyst system for the one-pot desymmetrization/oxidation of meso-1,2-alkane diols
Mueller, Christian E.,Hrdina, Radim,Wende, Raffael C.,Schreiner, Peter R.
supporting information; experimental part, p. 6309 - 6314 (2011/08/07)
Two is better than one: We demonstrate the viability of an organocatalytic reaction sequence along a short peptide backbone that carries two independent catalytic functionalities, which allow the rapid, one-pot acylative desymmetrization and oxidation of meso-alkane-1,2-diols to the corresponding acetylated acetoins with good yields and enantioselectivities (see scheme). Copyright
