2967-83-1Relevant articles and documents
An Asymmetric SN2 Dynamic Kinetic Resolution
Rezayee, Nomaan M.,Enem?rke, Valdemar J.,Linde, Sif T.,Lamhauge, Johannes N.,Reyes-Rodríguez, Gabriel J.,J?rgensen, Karl Anker,Lu, Chenxi,Houk
supporting information, p. 7509 - 7520 (2021/05/26)
The SN2 reaction exhibits the classic Walden inversion, indicative of the stereospecific backside attack of the nucleophile on the stereogenic center. Observation of the inversion of the stereocenter provides evidence for an SN2-type displacement. However, this maxim is contingent on substitution proceeding on a discrete stereocenter. Here we report an SN2 reaction that leads to enantioenrichment of product despite starting from a racemic mixture of starting material. The enantioconvergent reaction proceeds through a dynamic Walden cycle, involving an equilibrating mixture of enantiomers, initiated by a chiral aminocatalyst and terminated by a stereoselective SN2 reaction at a tertiary carbon to provide a quaternary carbon stereocenter. A combination of computational, kinetic, and empirical studies elucidates the multifaceted role of the chiral organocatalyst to provide a model example of the Curtin-Hammett principle. These examples challenge the notion of enantioenriched products exclusively arising from predefined stereocenters when operating through an SN2 mechanism. Based on these principles, examples are included to highlight the generality of the mechanism. We anticipate the asymmetric SN2 dynamic kinetic resolution to be used for a variety of future reactions.
Continuous Flow Synthesis of Terminal Epoxides from Ketones Using in Situ Generated Bromomethyl Lithium
Von Keutz, Timo,Cantillo, David,Kappe, C. Oliver
supporting information, p. 10094 - 10098 (2019/12/24)
A scalable procedure for the direct preparation of epoxides from ketones has been developed. The method is based on the carefully controlled generation of (bromomethyl)lithium (LiCH2Br) from inexpensive CH2Br2 and MeLi in a continuous flow reactor. The reaction has shown excellent selectivity for a variety of substrates, including α-chloroketones, which typically fail under classic Corey-Chaykovsky conditions. This advantage has been used to develop a novel route toward the drug fluconazole.
Mild Iridium-Catalysed Isomerization of Epoxides. Computational Insights and Application to the Synthesis of β-Alkyl Amines
Cabré, Albert,Cabezas-Giménez, Juanjo,Sciortino, Giuseppe,Ujaque, Gregori,Verdaguer, Xavier,Lledós, Agustí,Riera, Antoni
supporting information, p. 3624 - 3631 (2019/07/10)
The isomerization of epoxides to aldehydes using the readily available Crabtree's reagent is described. The aldehydes were transformed into synthetically useful amines by a one-pot reductive amination using pyrrolidine as imine-formation catalyst. The reactions worked with low catalyst loadings in very mild conditions. The procedure is operationally simple and tolerates a wide range of functional groups. A DFT study of its mechanism is presented showing that the isomerization takes place via an iridium hydride mechanism with a low energy barrier, in agreement with the mild reaction conditions. (Figure presented.).
Biocatalytic Parallel Interconnected Dynamic Asymmetric Disproportionation of α-Substituted Aldehydes: Atom-Efficient Access to Enantiopure (S)-Profens and Profenols
Tassano, Erika,Faber, Kurt,Hall, Mélanie
supporting information, p. 2742 - 2751 (2018/07/29)
The biocatalytic asymmetric disproportionation of aldehydes catalyzed by horse liver alcohol dehydrogenase (HLADH) was assessed in detail on a series of racemic 2-arylpropanals. Statistical optimization by means of design of experiments (DoE) allowed the identification of critical interdependencies between several reaction parameters and revealed a specific experimental window for reaching an ′optimal compromise′ in the reaction outcome. The biocatalytic system could be applied to a variety of 2-arylpropanals and granted access in a redox-neutral manner to enantioenriched (S)-profens and profenols following a parallel interconnected dynamic asymmetric transformation (PIDAT). The reaction can be performed in aqueous buffer at ambient conditions, does not rely on a sacrificial co-substrate, and requires only catalytic amounts of cofactor and a single enzyme. The high atom-efficiency was exemplified by the conversion of 75 mM of rac-2-phenylpropanal with 0.03 mol% of HLADH in the presence of ～0.013 eq. of oxidized nicotinamide adenine dinucleotide (NAD+), yielding 28.1 mM of (S)-2-phenylpropanol in 96% ee and 26.5 mM of (S)-2-phenylpropionic acid in 89% ee, in 73% overall conversion. Isolated yield of 62% was obtained on 100 mg-scale, with intact enantiopurities. (Figure presented.).
Synthesis of chiral butenolides using amino-thiocarbamate-catalyzed asymmetric bromolactonization
Tan, Chong Kiat,Er, Jun Cheng,Yeung, Ying-Yeung
, p. 1243 - 1246 (2014/02/14)
The asymmetric cyclization of 4,4-disubstituted 3-butenoic acids is studied. Amino-thiocarbamates are used as the catalysts and N-bromosuccinimide is used as the stoichiometric halogen source. The resulting γ-butanolide products are readily converted into the corresponding γ-butenolides (up to 58% ee) derivatives in one-pot.
Isomerization of terminal epoxides by a [Pd-H] catalyst: A combined experimental and theoretical mechanistic study
Vyas, Devendra J.,Larionov, Evgeny,Besnard, Celine,Guenee, Laure,Mazet, Clement
supporting information, p. 6177 - 6183 (2013/06/04)
An unusual palladium hydride complex has been shown to be a competent catalyst in the isomerization of a variety of terminal and internal epoxides. The reaction displayed broad scope and synthetic utility. Experimental and theoretical evidence are provided for an unprecedented hydride mechanism characterized by two distinct enantio-determining steps. These results hold promise for the development of an enantioselective variant of the reaction.
β-tert-Butyl aspartate as an organocatalyst for the asymmetric α-amination of α,α-disubstituted aldehydes
Theodorou, Alexis,Papadopoulos, Giorgos N.,Kokotos, Christoforos G.
supporting information, p. 5438 - 5443 (2013/07/05)
The enantioselective α-amination reaction of α,α- disubstituted aldehydes can lead to a variety of enantioenriched amino aldehydes, amino alcohols, and amino acids. After screening a variety of amino acids and their derivatives, we identified a cheap, simple, commercially available aspartic acid derivative that can catalyze efficiently the reaction between α,α-disubstituted aldehydes and dialkyl azodicarboxylates. The reaction proceeds smoothly leading to the corresponding α-aminated adducts in moderate to quantitative yields and moderate to high enantioselectivities (up to 96% ee). Finally, the conversion of these adducts to α,α-disubstituted quaternary amino acids is also described.
Catalytic hydrogen atom transfer (HAT) for sustainable and diastereoselective radical reduction
Gansaeuer, Andreas,Klatte, Max,Braendle, Gerhard M.,Friedrich, Joachim
supporting information; experimental part, p. 8891 - 8894 (2012/10/08)
Going cyclic! A catalytic cycle and cyclic transition states enable a novel sustainable and catalytic hydrogen atom transfer (HAT) for highly diastereoselective radical reductions. Readily available nontoxic silanes are the terminal reductants for epoxides that are opened by bifunctional titanocene(III) hydride catalysts. Copyright
Resolution of 2,2-disubstituted epoxides via biocatalytic azidolysis
Molinaro, Carmela,Guilbault, Audrey-Anne,Kosjek, Birgit
supporting information; experimental part, p. 3772 - 3775 (2010/11/16)
A practical procedure for the enzymatic resolution of 2-alkyl-2-aryl- disubstituted epoxides using the Codex HHDH P2E2 enzyme and sodium azide is reported. This method allowed the synthesis of novel regio-and enantioselective 1-azido-2-arylpropan-2-ols in
AZEPINO [4, 5-B] INDOLES AND METHODS OF USE
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Page/Page column 252, (2010/05/14)
This disclosure relates to new azepino[4,5-b]indole compounds that may be used to modulate a histamine receptor in an individual. Novel compounds are described, including new 1, 2,3,4,5, 6-tetrahydroazepino[4,5-b]indoles. Pharmaceutical compositions are also provided.
