- Selective Isomerization via Transient Thermodynamic Control: Dynamic Epimerization of trans to cis Diols
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Traditional approaches to stereoselective synthesis require high levels of enantio- and diastereocontrol in every step that forms a new stereocenter. Here, we report an alternative approach, in which the stereochemistry of organic substrates is selectivel
- Macmillan, David W. C.,Oswood, Christian J.
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- Investigation of Electrostatic Interactions towards Controlling Silylation-Based Kinetic Resolutions
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Electrostatic interactions between a silylated isothiourea intermediate and an ester π system were explored by determining how variations in sterics and electronics affect the selectivity of a silylation-based kinetic resolution. Sterics on the π systems affect the selectivity factors of alkyl 2-hydroxycyclohexanecarboxylates, resulting in a strong correlation of selectivity factors to Charton values. Induction effects of electron-withdrawing substituents on phenyl esters significantly enhance selectivity supporting an edge to face π–π interaction. The linear free energy relationships that were uncovered will aid in future incorporation of intermolecular electrostatic interactions towards controlling asymmetric reactions.
- Zhang, Tian,Redden, Brandon K.,Wiskur, Sheryl L.
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supporting information
p. 4827 - 4831
(2019/08/12)
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- Chemoenzymatic approaches to the synthesis of the (1S,2R)-isomer of benzyl 2-hydroxycyclohexanecarboxylate
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We examined ten strains of cultured whole-cell yeasts for the asymmetric reduction of commercially available ethyl 2-oxocyclohexanecarboxylate, and found that the (1S,2S)-stereoisomer of ethyl 2-hydroxycyclohexanecarboxylate was the major stereoisomer produced by Williopsis californica JCM 3600. The ethyl group of the ester was then substituted with a benzyl group with low volatility and increased hydrophobicity to facilitate the isolation of the expected product. Incubation with W. californica furnished benzyl (1S,2S)-2-hydroxycyclohexanecarboxylate (>99.9% ee) in 51.0% yield together with its (1R,2S)-isomer (>99.9% ee) in 35.4% yield. Upon treatment of the same substrate bearing the benzyl ester with a screening kit of purified overexpressed carbonyl reductases (Daicel Chiralscreen OH), two enzymes (E031, E078) furnished the (1R,2S)-isomer as the major product. With another enzyme (E007), the (1S,2R)-isomer was obtained, but its ee was very low (25.6%). The highly enantiomerically enriched (1S,2S)-isomer obtained by W. californica was transformed to the (1S,2R)-isomer (>99.9% ee), whose availability until now has been low, in 43.3% yield over two steps involving tosylation and subsequent inversive attack with tetrabutylammonium nitrite.
- Tsunekawa, Ryuji,Hanaya, Kengo,Higashibayashi, Shuhei,Shoji, Mitsuru,Sugai, Takeshi
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- SN2 Reactions at Tertiary Carbon Centers in Epoxides
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Described herein is a novel concept for SN2 reactions at tertiary carbon centers in epoxides without activation of the leaving group. Quantum chemical calculations show why SN2 reactions at tertiary carbon centers are proceeding in these systems. The reaction allows flexible synthesis of 1,3-diol building blocks for natural product synthesis with excellent control of the relative and absolute configurations.
- Zhang, Yong-Qiang,Poppel, Christina,Panfilova, Anastasia,Bohle, Fabian,Grimme, Stefan,Gans?uer, Andreas
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supporting information
p. 9719 - 9722
(2017/08/08)
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- Regioselective mono-deprotection of di-ferf-butylsilylene acetal derived from 1,3-diol with ammonium fluoride
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Here we report a novel and efficient method for the regioselective mono-deprotection of di-terf-butylsilylene acetals derived from 1,3-diols consisting of primary and secondary alcohols. The ammonium fluoride-mediated reactions of pyripyropene A derivative, thymidine and uridine derivatives, methyl β-D-glucofuranoside, and pyranoside derivatives each gave the corresponding primary alcohol with high regioselectivity.
- Ohtawa, Masaki,Tomoda, Hiroshi,Nagamitsu, Tohru
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p. 113 - 118
(2014/02/14)
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- Synthesis and characterization of the enantiomerically pure cis- and trans-2,4-dioxa-3-fluoro-3-phosphadecalins as inhibitors of acetylcholinesterase
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The title compounds, the P(3)-axially- and P(3)-equatorially-substituted cis- and trans-configured 3-fluoro-2,4-dioxa-3-phosphadecalin 3-oxides (= 3-fluoro-2,4-dioxa-3-phosphabicyclo[4.4.0]decane 3-oxides) have been prepared (ee > 99%) and fully character
- Waechter, Michael,Rueedi, Peter
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experimental part
p. 283 - 294
(2010/04/23)
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- Platinum-triethylamine-catalyzed hydrogenation of aldehydes and cyclohexanones
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The first hydrogenation of aldehydes and chemoselective hydrogenation of cyclohexanones catalyzed by PtO2-Et3N are presented. An additionally attractive feature of this hydrogenation is being applicable to the complicated molecules. Three equivalent of triethylamine and 0.05 equiv of PtO2 in 95% ethanol are found to be the optimal condition.
- Gao, Feng,Chen, Qiao-Hong,Wang, Feng-Peng
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supporting information; experimental part
p. 5270 - 5273
(2009/12/24)
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- Reductions of cyclic β-keto esters by individual Saccharomyces cerevisiae dehydrogenases and a chemo-enzymatic route to (1R,2S)-2-methyl-1-cyclohexanol
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Twenty purified dehydrogenases cloned from bakers' yeast (Saccharomyces cerevisiae) and expressed as fusion proteins with glutathione (S)-transferase were tested for their ability to reduce three homologous cyclic β-keto esters. The majority of dehydrogenases reduced ethyl 2-oxo-cyclopentanecarboxylate, yielding a pair of diastereomeric alcohols with consistent (1R)-stereochemistry. Ethyl 2-oxo-cyclohexanecarboxylate reductions afforded only cis-alcohol enantiomers. Ethyl 2-oxo-cycloheptanecarboxylate was accepted by two enzymes in the collection, and both yielded mainly the cis-(1R,2S)-alcohol. Escherichia coli cells overexpressing the YDL124w gene were used in a dynamic kinetic resolution of ethyl 2-oxo-cyclohexanecarboxylate to produce the key intermediate in a chemo-enzymatic synthesis of (1R,2S)-2-methyl-1-cyclohexanol, an important chiral building block.
- Padhi, Santosh Kumar,Kaluzna, Iwona A.,Buisson, Didier,Azerad, Robert,Stewart, Jon D.
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p. 2133 - 2138
(2008/02/11)
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- 1,2-Disubstituted cyclohexane carbocyclic analogues of nucleosides
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Several compounds of a new series of cyclohexane-based 1,2-disubstituted carbonucleoside analogues, were synthesized. The adenine and uridine derivatives, were prepared by construction of the heterocyclic base on the primary amino group of 2-aminocyclohexylmethanol, and the thymine derivative by condensation of 2-hydroxycyclohexylmethanol with thymine using the Mitsunobu reaction.
- Vina,Santana,Uriarte
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p. 1363 - 1365
(2007/10/03)
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- Stereoselective synthesis of novel anti-MRSA tricyclic carbapenems (trinems)
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(4S)-Hydroxymethyltrinem 3 was prepared via stereoselective aldol-type reaction with optically pure (R)-2-t-butyldimethylsilyloxymethylcyclohexanone ((R)-16). (4S)-Hydroxymethyltrinem 3 was converted into various kinds of trinem derivatives with anti-MRSA activity by using the Mitsunobu reaction. (C) 2000 Elsevier Science Ltd.
- Kanno, Osamu,Kawamoto, Isao
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p. 5639 - 5648
(2007/10/03)
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- Tethered α-boryl radical cyclizations of haloalkyl boronates
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Boroalkyl radicals readily cyclize onto alkenyl and alkynyl traps tethered via a C-B-O linkage. Oxidative cleavage of the C-B bond of the temporary connection following cyclization affords 1,3-diols in good yields.
- Batey, Robert A.,Smil, David V.
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p. 9183 - 9187
(2007/10/03)
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- Stereochemistry of the Inhibition of δ-Chymotrypsin with Optically Active cis-Decaline-Type Organophosphates: 31P-NMR Studies
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Investigation of the inhibition of δ-chymotrypsin with the four novel, optically active, axially and equatorially substituted cis-3-(2,4-dinitrophenoxy)-2,4-dioxa-3λ 5-phosphabicyclo[4.4.0]decan-3-ones (= 3-(2,4-dinitrophenoxy)hexahydro-4H-1,3,
- Furegati, Stefan,Ganci, Walter,Przibille, Georg,Rüedi, Peter
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p. 1127 - 1138
(2007/10/03)
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- Catalytic Cyclization/Silylation of Dienes Containing 1,1-Disubstituted Olefins Using Organolanthanide and Group 3 Organometallic Complexes
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The catalytic cyclization/silylation reaction of hindered dienes has been investigated using the relatively unhindered complexes Me2Si(C5H3SiMe3) 2YCH(TMS)2 and [CpTMS2LnMe]2 (Ln = Y, Lu). A wide variety of dienes and trienes bearing a number of functional groups were cychzed, affording silanes containing quaternary centers in a diastereoselective fashion and in good yield. The products can be oxidized using one of several different protocols, yielding alcohols for further functionalization.
- Molander, Gary A.,Dowdy, Eric D.,Schumann, Herbert
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p. 3386 - 3396
(2007/10/03)
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- 32. Stereochemistry of the Inhibition of δ-Chymotrypsin with Optically Active Bicyclic Organophosphates: 31P-NMR Studies
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The inhibition of δ-chymotrypsin with optically active, axially and equatorially substituted trans-3-(2,4-dini-trophenoxy)-2,4-dioxa-3λ 5-phosphabicyclo[4.4.0]decan-3-ones (= hexahydro-4H-1,3,2-benzodioxaphosphorin 3-oxides) was investigated. Their inhibitory power was determined by kinetic measurements, and the stereochemical course of the reaction of stoichiometric amounts of the enzyme and inhibitor was monitored with 31P-NMR spectroscopy at pH 7.8. The irreversible inhibitors show significant enantioselectivity (the (Sp)-enantiomer reacting faster) and yield diastereoisomeric, covalently phosphorylated derivatives of δ-chymotrypsin. 31P-NMR Spectroscopic studies of the inhibition by the axially substituted inhibitor revealed for the racemic (±)-2a first a resonance at -4.4 ppm and later, while inhibition proceeded, a second one at -4.5 ppm. The reaction with optically active (+)-2a showed only one signal at -4.4 ppm and its enantiomer (-)-2a only one signal at -4.5 ppm. Using the equatorially substituted racemic epimer (±)-2b, we observed the main resonance at -5.3 ppm and two minor ones at -4.4 and -4.5 ppm. The optically active compound (+)-2b showed two peaks at -4.5 and -5.3 ppm, whereas its antipode (-)-2b revealed two signals at -4.4 and -5.3 ppm. Comparing the 31P chemical shifts of the corresponding covalent phosphoserine derivatives 4a ( -5.7 ppm, axial) and 4b (-4.5ppm, equatorial) shows the inhibition with the axial compounds 2a to proceed via neat inversion of the configuration at the P-atom. whereas the equatorial epimers 2b with a higher conformational flexibility seem to follow a different stereochemical pathway which results in both inversion and retention.
- Ganci, Walter,Meier, Eric J. M.,Merckling, Franco A.,Przibille, Georg,Ringeisen, Urs,Rueedi, Peter
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p. 421 - 435
(2007/10/03)
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- A chemoenzymatic preparation of both enantiomers of ω-hydroxymethyl-substituted lactones
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(R)- and (S)-δ-hydroxymethyl valerolactone and ε-hydroxymethyl caprolactone were prepared as tert-butyldiphenylsilyl derivatives, in good yield and high enantiomeric purities, in a 5 step sequence, starting from the microbial stereospecific reduction of ethyl 2-oxocyclopentane or 2-oxocyclohexane carboxylates respectively.
- Buisson, Didier,Azerad, Robert
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- Facile synthesis of optically active 2-hydroxymethyl-4-methylenecyclohexanol. De novo synthesis of dideoxycarbocyclic sugars
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Treatment of the olefinic epoxy alcohol 4 with diethylaluminum fluoride gives the hydroxymethyl methylenecyclohexanol 5 in yields of 60-75% rather than the other possible epoxide opening product 6 presumably due to a geometrical constraint similar to that in Baldwin's rules for ring closure.
- Jung, Michael E.,Cho, Young M.,Jung, Young H.
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- Hindered organoboron groups in organic chemistry. 21. The reactions of dimesitylboron stabilised carbanions with oxiranes
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Dimesitylboron stabilised carbanions react with oxiranes to give products that can be oxidised to 1,3-diols. The reactions are, in general, under steric rather than electronic control, and proceed smoothly for all but tetrasubstituted oxiranes. Some unusual stereoselective effects have been observed.
- Peter, Andrew,Vaughan-Williams, Gina F.,Rosser, Richard M.
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p. 3007 - 3034
(2007/10/02)
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- Solvent Effects on Keto-Enol Equilibria: Tests of Quantitative Models
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The effect of solvent on the equilibrium constants between selected keto-enol isomer pairs has been determined.The protomeric systems studied are 5,5-dimethyl-1,3-cyclohexanedione (1), 2-methyl-1,3-cyclohexanedione (3), 3-oxabicyclo-2,9-dioxononane (5), 2,4-pentanedione (7), ethyl 3-oxobutanoate (9), and 9-anthracenone (11).A wide variety of theoretical and empirical solvation parameters have been tested in a multiparameter linear free energy format to model the changes in equilibria.The most successful correlations are obtained with the Kamlet-Taft polarity-polarizability and hydrogen-bonding terms, although the Swain A and B factors have advantages in same cases.In general, for the isomer pairs in which the enol cannot form an internal hydrogen bond (1-2, 3-4, and 11-12), the equilibria appear to be controlled almost completely by the hydrogen-bonding basicity of the solvent.For the isomer pairs 5-6, 7-8, and 9-10, in which intramolecular hydrogen bonding is possible, the polarity-polarizability effect dominates, although differential stabilization of the isomers by hydrogen bonding remains significant.
- Mills, Sander G.,Beak, Peter
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p. 1216 - 1224
(2007/10/02)
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- THE DIMESITYLBORON GROUP IN ORGANIC SYNTHESIS 8. PREPARATION OF 1,3-DIOLS FROM OXIRANES
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Alkyldimesitylboranes, yield anions, Mes2BCHR, that on reaction with oxiranes followed by oxidation give 1,3-diols.These anions are thus the operational equivalent of RCHOH.The scope and limitations of the new process are delineated.
- Pelter, Andrew,Bugden, Gina,Rosser, Richard
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p. 5097 - 5100
(2007/10/02)
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- Silylmethyl Radical Cyclization: New Stereoselective Method for 1,3-Diol Synthesis from Allylic Alcohols
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Cyclizations of (bromomethyl)dimethylsilyl allylic ethers by treatment with tri-n-butyltin hydride in a free-radical process followed by oxidation in a one-pot manner with hydrogen peroxide gave th corresponding 1,3-diols predominantly with high stereoselectivity.
- Nishiyama, Hisao,Kitajima, Toshio,Matsumoto, Makoto,Itoh, Kenji
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p. 2298 - 2300
(2007/10/02)
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- Asymmetric Diels-Alder Reaction: Applications of Chiral Dienophiles
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The chiral dienophile recently designed and its related compounds react highly diastereoselectively with a wide variety of both achiral and chiral dienes, and the stereochemical outcome of these Diels-Alder reactions is predictable.
- Masamune, Satoru,Reed, Lawrence A.,Davis, Jeffery T.,Choy, William
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p. 4441 - 4444
(2007/10/02)
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- Phosphorylated Sugars. Part 23. Synthesis and Reactions of Phosphodiesters containing 2-Aminoethanol and a Polyfunctional Alcohol and their Behaviour during Acid- and Base-catalysed Hydrolysis
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Phosphodiesters of 2-aminoethanol and of polyhydroxylated alcohols and sugars have been synthesised; their behaviour in M-HCl and in saturated (ca. 0.2 M) Ba(OH)2 solutions at 100 deg C have been examined.With the exception of 2-aminoethyl ethyl phosphate which, in acidic medium, yielded 2-aminoethylphosphate, free 2-aminoethanol and phosphorylated polyols or sugars were the main products formed.Because of simultaneously and/or sequentially occurring reactions the structures of the phosphorylated derivatives formed gave no unambiguous information regarding the structure of the initial phosphodiester.
- Trigalo, Francois,Szabo, Ladislas
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p. 1733 - 1744
(2007/10/02)
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