- Dynamic kinetic resolution of a tertiary alcohol
-
In spite of the tremendous success of dynamic kinetic resolutions for a broad range of compound classes, tertiary alcohols and their corresponding esters have still remained as one of the most challenging substrates for this type of process. This is due t
- Akai, Shuji,Gr?ger, Harald,Kühn, Franziska,Katsuragi, Satoko,Oki, Yasuhiro,Scholz, Cedric
-
supporting information
p. 2885 - 2888
(2020/03/23)
-
- Transition-Metal-Free Radical Hydrotrifluoromethylation of Alkynes
-
A combination of readily available and bench-stable CF3SO2Na and tBuOOH was efficiently used for hydrotrifluoromethylation of alkynes. An excellent trans-selectivity was demonstrated in the synthesis of alkenes. The developed mild reaction conditions allow the supression of the competing Meyer–Schuster-type rearrangement.
- Matcha, Kiran,Antonchick, Andrey P.
-
supporting information
p. 309 - 312
(2019/01/24)
-
- Catalytic Synthesis of Trifluoromethylated Allenes, Indenes, Chromenes, and Olefins from Propargylic Alcohols in HFIP
-
A general method to access CF3-substituted allenes from propargylic alcohols under Lewis acid catalysis in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvent is described. By tuning the reaction time and temperature, the obtained allenes rearr
- No?l, Florent,Vukovi?, Vuk D.,Yi, Jing,Richmond, Edward,Kravljanac, Pavle,Moran, Joseph
-
p. 15926 - 15947
(2019/12/25)
-
- Palladium-Catalyzed Carboamination of Allylic Alcohols Using a Trifluoroacetaldehyde-Derived Tether
-
The selective palladium-catalyzed carboamination of allylic alcohols is reported on the basis of the use of an easily introduced trifluoroacetaldehyde-derived tether. Aminoalkynylation reactions were realized using alkynyl bromides and commercially available phosphine ligands. For aminoarylations, a new biaryl phosphine ligand, "Fu-XPhos", was introduced to overcome a competitive Heck pathway. The carboamination products were obtained in high yields and diastereoselectivity. The tether could be easily removed to give value-added amino alcohol building blocks.
- Muriel, Bastian,Orcel, Ugo,Waser, Jerome
-
supporting information
p. 3548 - 3551
(2017/07/17)
-
- Construction of Chiral Tri- and Tetra-Arylmethanes Bearing Quaternary Carbon Centers: Copper-Catalyzed Enantioselective Propargylation of Indoles with Propargylic Esters
-
Copper-catalyzed enantioselective propargylation of indoles with propargylic esters and sequential Huisgen cycloaddition with azides lead to the construction of chiral triarylmethanes, bearing a quaternary carbon center, with high to excellent enantioselectivities. The result described herein can be used in the enantioselective preparation of a tetraarylmethane.
- Tsuchida, Kouhei,Senda, Yasushi,Nakajima, Kazunari,Nishibayashi, Yoshiaki
-
supporting information
p. 9728 - 9732
(2016/08/10)
-
- Synthesis of Trifluoromethyl-allenes by Gold-Catalyzed Rearrangement of Propargyl Benzyl Ethers
-
A new method for the synthesis of trifluoromethyl-allenes from easily accessible α-trifluoromethyl-propargyl benzyl ether derivatives following a gold-catalyzed intramolecular hydride transfer has been developed. Various di- and trisubstituted trifluoromethyl-allenes were obtained in good to excellent yields.
- Boreux, Arnaud,Lonca, Geoffroy H.,Riant, Olivier,Gagosz, Fabien
-
supporting information
p. 5162 - 5165
(2016/10/14)
-
- One-Pot Three-Component Synthesis of Vicinal Diamines via In Situ Aminal Formation and Carboamination
-
A synthesis of vicinal diamines via in situ aminal formation and carboamination of allyl amines is reported. Employing highly electron-poor trifluoromethyl aldimines in their stable hemiaminal form was key to enable both a fast and complete aminal formation as well as the palladium-catalyzed carboamination step. The conditions developed allow the introduction of a wide variety of alkynyl, vinyl, aryl, and hetereoaryl groups with complete regioselectivity and high diastereoselectivity. The reaction exhibits a high functional-group tolerance. Importantly, either nitrogen atom of the imidazolidine products can be selectively deprotected, while removal of the aminal tether can be achieved in a single step under mild conditions to reveal the free diamine. We expect that this work will promote the further use of mixed aminal tethers in organic synthesis.
- Orcel, Ugo,Waser, Jerome
-
supporting information
p. 12881 - 12885
(2016/10/04)
-
- Kinetic resolution of esters from secondary and tertiary benzylic propargylic alcohols by an improved esterase-variant from Bacillus sp. BP-7
-
We described in a recent work the rational improvement of an esterase from Bacillus sp. BP7 aimed at investigating the efficiency of several esterase variants for enantiomeric resolution of acetate esters of tertiary alcohols. Variant EstBP7-AGA, bearing two aminoacidic changes in the oxyanion hole, showed an excellent E?>?100 enantioselectivity value towards a complex tertiary alcohol acetate (2-(4-pyridyl)-3-butyn-2-yl acetate) at low reaction temperature (4?°C). We here go further in the investigation of such esterase variant by analyzing the kinetic resolution of benzylic propargylic esters to prove that this enzyme is a powerful tool to obtain enantiomerically pure tertiary as well as secondary alcohols, provided that the structural integrity of the parent benzylic propargylic ester is maintained. Understanding the mode of action and interaction of such esterase variant with the assayed substrates will allow production of interesting pharmaceutical building blocks.
- Fillat, Amanda,Romea, Pedro,Pastor, F.I. Javier,Urpí, Fèlix,Diaz, Pilar
-
-
- Platinum catalysed hydrosilylation of propargylic alcohols
-
A facile and user-friendly protocol has been developed for the selective synthesis of E-vinyl silanes derived from propargylic alcohols using a PtCl 2/XPhos catalyst system. The reaction is generally high yielding and provides a single regioiso
- McAdam, Catherine A.,McLaughlin, Mark G.,Johnston, Adam J. S.,Chen, Jun,Walter, Magnus W.,Cook, Matthew J.
-
supporting information
p. 4488 - 4502
(2013/08/23)
-
- Characterization of a novel esterase isolated from intertidal flat metagenome and its tertiary alcohols synthesis
-
A gene coding for an esterase (EstEH112) was isolated from metagenome originated from Korean intertidal flat sediment. The putative esterase gene encoded a 340 amino acids protein with characteristic residues of lipolytic enzymes such as a conserved pentapeptide (GXSXG), the typical catalytic S-D-H triad, and a GGG(A)X-motif in the oxyanion hole near the active site similar to the hormone sensitive lipase (HSL) family. p-Nitrophenyl butyrate was the best substrate for the enzyme among the other p-nitrophenyl esters investigated. The apparent optimal temperature and pH for EstEH112 was 35°C and at pH 8.0, respectively. EstEH112 efficiently catalyzed the hydrolysis of various large tertiary alcohol esters. These characteristics of EstEH112 make it a potential candidate for application in biocatalysis.
- Oh, Ki-Hoon,Nguyen, Giang-Son,Kim, Eun-Young,Kourist, Robert,Bornscheuer, Uwe,Oh, Tae-Kwang,Yoon, Jung-Hoon
-
experimental part
p. 67 - 73
(2012/09/07)
-
- Identification of novel esterases for the synthesis of sterically demanding chiral alcohols by sequence-structure guided genome mining
-
Six esterases isolated from sequence and structure-guided genome mining approaches were evaluated for the kinetic resolution of secondary and tertiary alcohols that find application in the fine chemical and pharmaceutical industries. Activity and enantios
- Nguyen, Giang-Son,Thompson, Mark L.,Grogan, Gideon,Bornscheuer, Uwe T.,Kourist, Robert
-
scheme or table
p. 88 - 94
(2012/02/02)
-
- Hydrolase-catalyzed stereoselective preparation of protected α,α-dialkyl-α-hydroxycarboxylic acids
-
The title compounds were prepared by a Passerini multi-component reaction and subjected to enzymatic kinetic resolution using 40 enzymes known to be active towards esters of tertiary alcohols. This identified a protease (P1), a thermophilic esterase (PestE) and an esterase of metagenome origin (esterase 8) as the most active and enantioselective biocatalysts. After further optimization of reaction conditions, two compounds were prepared in preparative scale using esterase 8 yielding (+)-1-(tert-butylamino)-2-methyl-1-oxobutyl-2-yl acetate with 93%ee and (-)-1-(tert-butylamino)-2-trifluoro-methyl-1-oxobutyl-2-yl acetate with 47%ee.
- Kourist, Robert,Nguyen, Giang-Son,Struebing, Dirk,Boettcher, Dominique,Liebeton, Klaus,Naumer, Christian,Eck, Juergen,Bornscheuer, Uwe T.
-
p. 1839 - 1843
(2008/12/22)
-
- Complete inversion of enantioselectivity towards acetylated tertiary alcohols by a double mutant of a Bacillus subtilis esterase
-
(Chemical Equation Presented) Simultaneous saturation mutagenesis at three amino acid residues of esterase BS2 followed by high-throughput screening identified a double mutant (E188W/M193C) with inverted enantiopreference, high E values, and broadened sub
- Bartsch, Sebastian,Kourist, Robert,Bornscheuer, Uwe T.
-
p. 1508 - 1511
(2008/12/23)
-
- Highly enantioselective synthesis of arylaliphatic tertiary alcohols using mutants of an esterase from Bacillus subtilis
-
The kinetic resolution of a series of acetates of arylaliphatic tertiary alcohols was studied using recombinant esterase variants from Bacillus subtilis (BS2) expressed in E. coli. Highest enantioselectivities (E > 100) were achieved in the synthesis of 1
- Kourist, Robert,Bartsch, Sebastian,Bornscheuer, Uwe T.
-
p. 1393 - 1398
(2008/03/28)
-
- Synthesis of alkyne derivatives of a novel triazolopyrazine as A 2A adenosine receptor antagonists
-
A novel [1,2,4]triazolo[1,5-a]pyrazine core was synthesized and coupled with terminal acetylenes. The structure-activity relationship of the alkynes from this novel template was studied for their in vitro and in vivo adenosine A2A receptor antagonism. Selected compounds from this series were shown to have potent in vitro and in vivo activities against adenosine A 2A receptor. Compound 12, in particular, was found to be orally active at 3 mg/kg in both a mouse catalepsy model and a 6-hydroxydopamine- lesioned rat model.
- Yao, Gang,Haque, Serajul,Sha, Li,Kumaravel, Gnanasambandam,Wang, Joy,Engber, Thomas M.,Whalley, Eric T.,Conlon, Patrick R.,Chang, Hexi,Kiesman, William F.,Petter, Russell C.
-
p. 511 - 515
(2007/10/03)
-
- Cross-linked crystals of Candida rugosa lipase: Highly efficient catalysts for the resolution of chiral esters
-
To date, most enzyme-based organic syntheses have employed enzymes in the form of a crude protein extract. The instability and expense of highly purified proteins has all but obviated their use as catalysts for enantioselective hydrolyses. Herein, we describe the use of the major hydrolase from commercial Candida rugosa lipase (CRL) in the form of a cross-linked enzyme crystal (CLEC) for the enantioselective hydrolysis of chiral racemic esters. The enantioselectivity of CRL-CLECs in the hydrolysis of many important chiral esters is vastly superior to that of the crude CRL extract. Since the CRL-CLEC is insoluble, recoverable, and 2-3 orders of magnitude more stable than the soluble protein, the CRL-CLEC is an attractive replacement for the crude enzyme preparation. The use of this catalyst in the resolution of chiral esters 1-11 and in the preparative scale (1a) and multicycle resolution (2a) of important anti-inflammatory drugs is described.
- Lalonde, Jim J.,Govardhan, Chandrika,Khalaf, Nazer,Martinez, Aldo G.,Visuri, Kalevi,Margolin, Alexey L.
-
p. 6845 - 6852
(2007/10/02)
-
- The synthesis of (R)-γ-phenyl-γ-(trifluoromethyl)-butyrolactone and (2R,3S)-1,1,1-trifluoro-2-methoxy-2-phenyl-3,4-epoxybutane in homochiral forms
-
(R)-γ-Phenyl-γ-(trifluoromethyl)-butyrolactone (1) and (2R,3S)-1,1,1-trifluoro-2-methoxy-2-phenyl-3,4-epoxybutane (2) have been prepared in high optical purity from the tertiary (S)-(3)-acetate which was resolved using the lipase from Candida cylindracea.
- O'Hagan,Zaidi,Lamont
-
p. 1703 - 1708
(2007/10/02)
-
- Hydrolytic Resolution of Tertiary Acetylenic Acetate Esters With the Lipase from Candida Cylindracea
-
The kinetic resolution of a series of tertiary acetylenic acetate esters using the lipase from Candida cylindracea has been explored.Compounds 6c and the trifluoromethyl acetate 6e have been resolved with high enantiomeric enrichment.Several other tertiary acetate esters carrying a CF3 group have been investigated which proved inert to enzymatic hydrolysis.From these results and published data, we are able to propose a predictive model for identifying the preferred enantiomer of secondary and tertiary trifluoromethyl acetate esters for this lipase.
- O'Hagan, David,Zaidi, Naveed A.
-
p. 947 - 949
(2007/10/02)
-
- Optically active propargyl alcohol derivative and a method for preparation of the same
-
An optically active propargyl alcohol derivative of the formula (I) STR1 wherein X=phenyl or thienyl and R=lower alkyl, halogenated methyl, phenyl or substituted phenyl having at least one lower alkyl radical and or halogen atom, is prepared by contacting a racemic modification of l- and d-isomers of the formula (I) with l-brucine in an organic solvent, by separating the resultant deposited diastereomer from a solution containing the resultant other diastereomer in the organic solvent, by decomposing each diastereomer with an aqueous mineral acid solution in the presence of an organic solvent capable of dissolving the corresponding optically active isomer dissociated from the diastereomer and incompatible with water so as to allow the optically active isomer to be dissolved in the water-incompatible organic solvent, and by recovering the optically active isomer from the solution thereof.
- -
-
-