Enantioselective Sulfoxidations Catalyzedby Horseradish Peroxidase, ManganesePeroxidase, and Myeloperoxidase

 Horseradish peroxidase (HRP), myeloperoxidase (MPO), and manganese peroxidase (MnP) have been shown to catalyze the asymmetric sulfoxidation of thioanisole. When H₂O₂ was added stepwise to MPO, a maximal yield of 78% was obtained at pH 5 (ee 23%), whereas an optimum in the enantiomeric excess (32%, (R)-sulfoxide) was found at pH 6 (60% yield). For MnP a yield of 18% and a high enantiomeric excess of 91% of the (S)-sulfoxide were obtained at pH 5 and a yield of 36% and an ee of 87% at pH 7.0. Optimization of the conversion catalyzed by horseradish peroxidase at pH 7.0 by controlled continuous addition of hydrogen peroxide during turnover and monitoring the presence of native enzyme as well as of intermediates I, II, and III led to the formation of the sulfoxide in high yield (100%) and moderate enantioselectivity (60%, (S)-sulfoxide).     

A Convenient One-Step Catalytic Method for Obtaining Optically Active 2-Cyclopentenyl Benzoate from Cyclopentene

(S)-2-Cyclopentenyl benzoate has been obtained in 54–67% yield and 54–59% enantiomeric excess (ee) by oxidation of cyclopentene with tert-butyl peroxybenzoate catalyzed by copper(I) oxide and (S)-proline.     

Facile Preparation of Chiral 1, 3‐Diols via Stereoselective Transfer Hydrogenation of 1, 3‐Diones

Asymmetric reduction of 1, 3‐diones catalyzed by (S, S)‐TsD‐PEN‐Ru(II) complex in a mixture of formic add‐triethylamine proceeded with a substrate/catalyst molar ratio of 100 to give (S, S)‐l,3‐diols with excellent diastereomeric (98.6% de) and enantiomeric purities ( > 99% ee). Other C₂‐symmetric diols were also obtained in almost quantitative yields with high diastereomeric (80.0%‐84.2% de) and enantiomeric purities ( > 99% ee).     

Enantioselectivity of enzymatic acylation of some structurally various racemic alcohols in anhydrous aprotic media

Partial acylation of (R,S)-3,7-dimethyloctan-1-ol (1) and (R,S)-7-methoxy-3,7-dimethyloctan-1-ol (2) with vinyl acetate catalyzed by the lipase fromCandida cylindracea affords in good yields the correspondingS-configured acetates with 92–98% enantiomeric excess (ee). Under similar conditions, racemic α-cyclogeraniol (3), drim-7-en-11-ol, methyl 4-(3-hydroxy-2-methylpropyl)benzoate, and its η⁶-chromium(tricarbonyl) complex (6) are acylated with rather poor (and, for the two latter, opposite) enantioselectivity, whereas (R,S)-2,4∶3,5-di-O-benzylidenexylitol remains unaffected. Racemic isoborneol (8) and 2-nitro-1-phenylethanol also remain almost or completely unconverted. Attempts to perform enantioselective acylation of alcohols 3 and 8 with Ac₂O in the presence of porcine pancreatic lipase (PPL) proved equally unsuccessful. By contrast, the PPL-catalyzed acylation of alcohol 6 with vinyl acetate at 17% conversion affords the levorotatory acetate (S)-6a withca. 100%ee. PPL-Mediated partial acylation of (R,S)-pantolactone with Ac₂O, followed by mild deacylation of the resultingR acetate, gives (R)-(-)-pantolactone of 97% enantiomeric purity in 60% overall yield. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 175–186, January, 1997.     

Optically Active Helical Poly[(S)‐3‐vinyl‐2,2′‐dihydroxy‐1,1′‐binaphthyl]: New Ligand for Asymmetric Addition of Diethylzinc to Aryl Aldehyde

Poly[(S)‐3‐vinyl‐2,2′‐dihydroxy‐1,1′‐binaphthyl] (L*) was obtained by taking off the protecting groups of poly[(S)‐3‐vinyl‐2,2′‐bis(methoxymethoxy)‐1,1′‐binaphthyl] (poly‐ 1 ). L* was proved to keep a stable helical conformation in solution. The application of helical L* in the asymmetric addition of diethylzinc to aldehydes has been studied. The catalytic system employing 10 mol% of L* and 150 mol% of Ti(OⁱPr)₄ was found to promote the addition of diethylzinc to a wide range of aromatic aldehydes, giving up to 99% enantiomeric excess (ee) and up to 93% yield of the corresponding secondary alcohol at 0°C. The chiral polymer can be easily recovered and reused without loss of catalytic activity as well as enantioselectivity.     

Highly Enantioselective Catalytic System for Asymmetric Copolymerization of Carbon Dioxide and Cyclohexene Oxide

A new ligand can be easily prepared, and its intramolecular dinuclear zinc complexes act as a high performance catalyst for the asymmetric alternating copolymerization of cyclohexene oxide and CO₂ under very mild conditions (1 atm CO₂, room temperature), affording completely alternating polycarbonates with up to 93.8 % enantiomeric excess (ee) and 98 % yield. A high M_n value of 28 600 and a relatively narrow polydispersity (M_w/M_n ratio) of 1.43 were also achieved.     

Cob(I)alamin als Katalysator, 5. Mitteilung [1]. Enantioselektive Reduktion α,β-ungesättigter Carbonylderivate

Cob(I)alamin as Catalyst. 5. Communication [1]. Enantioselective Reduction of α,β-Unsaturated Carbonyl Derivatives The cob(I)alamin-catalyzed reduction of an α,β-unsaturated ethyl ester in aqueous acetic acid produced the (S)-configurated saturated derivative 2 with an enantiomeric excess of 21%. The starting material 1 is not reduced at pH = 7.0 in the presence of catalytic amounts of cob(I)alamin (see Scheme 2). It is shown that the attack of cob(I)alamin and not of cob(II)alamin, also present in Zn/CH₃COOH/H₂O, accounts for the enantioselective reduction observed. All the (Z)-configurated starting materials 1 , 3 , 5 , 7 , 9 and 11 have been transformed to the corresponding (S)-configurated saturated derivatives 2 , 4 , 6 , 8 , 10 and 12 , respectively. The highest enantiomeric excess revealed to be present in the saturated product 12 (32,7%, S) derived from the (Z)-configurated methyl ketone 11 (see Scheme 3 and Table 1). The reduction of the (E)-configurated starting materials led mainly to racemic products. A saturated product having the (R)-configuration with a rather weak enantiomeric excess (5.9%) has been obtained starting from the (E)-configurated methyl ketone 23 (see Scheme 5 and Table 2). The allylic alcohols 16 and 24 have been reduced to the saturated racemic derivative 17 .     

Pseudomonas sp. Lipase Immobilized on Magnetic Porous Polymer Microspheres as an Effective and Recyclable Biocatalyst for Resolution of Allylic Alcohols

Magnetic porous polymeric microspheres containing epoxy groups were prepared by suspension polymerization (denoted as magnetic Fe₃O₄@GEM microspheres). Fe₃O₄@GEM with a specific surface area of 30.41 m²/g, average pore diameter of 17.13 nm, and pore volume of 0.13 cm³/g exhibited superparamagnetic behavior with the saturation magnetization of 7.1 emu/g. The content of epoxy groups on Fe₃O₄@GEM was 0.22 mmol/g. Pseudomonas sp. lipase (PSL) was covalently immobilized onto the Fe₃O₄@GEM microspheres through the reaction between the amino groups of the enzyme and the epoxy groups on the microspheres. PSL/Fe₃O₄@GEM exhibited enhanced enantioselectivity for the resolution of allylic alcohol to the corresponding optically active (S)‐allylic alcohol and (R)‐allylic alcohol acetate compared to free PSL. The enantiomeric excess of (S)‐l‐pheny‐2‐propen‐1‐ol for the former (98.1%) was 81.7 times that of the latter (1.2%) when the immobilized PSL was used for transesterification resolution of (R,S)‐l‐pheny‐2‐propen‐1‐ol. Furthermore, the ee_s and ee_p values were still retained at 95.2% and 95.4% after PSL/Fe₃O₄@GEM was recycled 10 times, indicating that PSL/Fe₃O₄@GEM had very good reusability. In addition, the transesterification resolution of (R,S)‐1‐(4‐methylphenyl)‐2‐propen‐1‐ol and (R,S)‐1‐(4‐bromophenyl)‐2‐propen‐1‐ol was catalyzed by PSL/Fe₃O₄@GEM, affording ideal ee_s and ee_p values of 99.3%, 97.4% and 99.6%, 98.2%, respectively. Therefore, PSL/Fe₃O₄@GEM demonstrated its potential as a highly efficient enzymatic reactor and Fe₃O₄@GEM would be very promising carriers for immobilizing enzymes in industrial application.     

Investigation of Functionalized α‐Chloroalkyllithiums for a Stereospecific Reagent‐Controlled Homologation Approach to the Analgesic Alkaloid (−)‐Epibatidine

Four putative functionalized α‐chloroakyllithiums RCH₂CHLiCl, where R=CHCH₂ ( 18 a ), CCH ( 18 b ), CH₂OBn ( 18 c ), and CH[O(CH₂)₂O] ( 18 d ), were generated in situ by sulfoxide–lithium exchange from α‐chlorosulfoxides, and investigated for the stereospecific reagent‐controlled homologation (StReCH) of phenethyl and 2‐chloropyrid‐5‐yl ( 17 ) pinacol boronic esters. Deuterium labeling experiments revealed that α‐chloroalkyllithiums are quenched by proton transfer from their α‐chlorosulfoxide precursors and it was established that this effect compromises the yield of StReCH reactions. Use of α‐deuterated α‐chlorosulfoxides was discovered to ameliorate the problem by retarding the rate of acid‐base chemistry between the carbenoid and its precursor. Carbenoids 18 a and 18 b showed poor StReCH efficacy, particularly the propargyl group bearing carbenoid 18 b , the instability of which was attributed to a facile 1,2‐hydride shift. By contrast, 18 d , a carbenoid that benefits from a stabilizing interaction between O and Li atoms gave good StReCH yields. Boronate 17 was chain extended by carbenoids 18 a , 18 b , and 18 d in 16, 0, and 68 % yield, respectively; α‐deuterated isotopomers D ‐ 18 a and D ‐ 18 d gave yields of 33 and 79 % for the same reaction. Double StReCH of 17 was pursued to target contiguous stereodiads appropriate for the total synthesis of (?)‐epibatidine ( 15 ). One‐pot double StReCH of boronate 17 by two exposures to (S)‐D ‐ 18 a (≤66 % ee), followed by work‐up with KOOH, gave the expected stereodiad product in 16 % yield (d.r.～67:33). The comparable reaction using two exposures to (S)‐D ‐ 18 d (≤90 % ee) delivered the expected bisacetal containing stereodiad (R,R)‐DD ‐ 48 in 40 % yield (≥98 % ee, d.r.=85:15). Double StReCH of 17 using (S)‐D ‐ 18 d (≤90 % ee) followed by (R)‐D ‐ 18 d (≤90 % ee) likewise gave (R,S)‐DD ‐ 48 in 49 % yield (≥97 % ee, d.r.=79:21). (R,S)‐DD ‐ 48 was converted to a dideuterated isotopomer of a synthetic intermediate in Corey’s synthesis of 15 .     

The role of chirality in directing the formation of cup-shaped porphyrins and the coordination characteristics of such hosts

Cup‐shaped porphyrin 1 a has four norbornane rings for encircling space and this type of host could be of interest in supramolecular and catalytic chemistry. We used ¹H NMR spectroscopy to investigate the acid‐catalyzed (pTsOH in CHCl₃ and TFA in CH₃CN) condensation of racemic, enantioenriched (80–85 % enantiomeric excess (ee)), and enantiopure (99 % ee) pyrromethanecarbinol 7 into 1 a . We found that the oligomerization of racemic 7 _rac would give 1 a–d in the ratio different from the statistical one, though a minuscule quantity of 1 a (<5 %) formed. The oligomerization of enantioenriched 7 (80–85 % ee), however, led to the formation of greater amounts of 1 a (31–47 %) along with other stereoisomers 1 b–d . Importantly, pTsOH catalyzed the conversion of enantiopure 7 (99 % ee) into 1 a (>95 % diastereomeric excess (de), 25 % overall yield) in CHCl₃ although prolonged reaction times or greater concentration of the catalytic acid gave rise to 1 b–d at the expense of 1 a . The metallation of 1 a with Zn(OAc)₂ led to the formation of Zn^II‐ 1 a and we used computational (DFT: RI‐BP86/SV(P),TZVP) and experimental (¹H NMR spectroscopy) methods to study the partitioning of smaller N‐methylimidazole 13 (94 ų) and bigger 1,5‐dicyclohexylimidazole 14 (268 ų) between the inner and outer side of the host. We found that bigger 14 was mostly encapsulated (90 %) inside Zn^II‐ 1 a at 298.0 K, whereas smaller 13 would equally partition between the two sides of the host. Furthermore, the out/in equilibrium was, in the case of 14 ‐Zn^II‐ 1 a , favored by entropy (TΔS°_out/in=3.5±0.1 kcal mol^?1) indicating that perhaps differential solvation of the coordinated ligand assisted the encapsulation.     

Mechanistic investigation of the Candida albicans CCT 0776 stereoinversion system and application to obtain enantiopure secondary alcohols

Phenylethanol deracemization with Candida albicans CCT 0776 whole cells yields the (R)-enantiomer in over 99% enantiomeric excess and 98% yield. The deracemization process involves, in the first step, a fast, highly (S)-selective oxidation (NADP and O₂ dependent) and, in the second step, a slower partially (S)-selective reduction (NADH dependent) of the intermediate ketone. The process was extended to other 2-alkanols, 1,2-diols and 1,3-diols and, with the exception of 1,3-diol (unreactive), the enantiomeric excess and yield of the deracemization were about 99% and 62–98%, respectively.     

Enantioselective Synthesis and Application to the Allylic Imidate Rearrangement of Amine‐Coordinated Palladacycle Catalysts of Cobalt Sandwich Complexes

The reaction of (η⁵‐(N,N‐dimethylaminomethyl)cyclopentadien‐yl)(η⁴‐tetraphenylcyclobutadiene)cobalt with sodium tetrachloropalladate and (R)‐N‐acetylphenylalanine gave planar chiral palladacycle di‐μ‐chloridebis[(η⁵‐(S_p)‐2‐(N,N‐dimethylaminomethyl)cyclopentadienyl,1‐C,3′‐N)(η⁴‐tetraphenylcyclobutadiene)cobalt]dipalladium [(S_p)‐Me₂‐CAP‐Cl] in 92 % ee and 64 % yield. Enantiopurity (>98 % ee) was achieved by purification of the monomeric (R)‐proline adducts and conversion back to the chloride dimer. Treatment with AgOAc gave (S_p)‐Me₂‐CAP‐OAc which was applied to asymmetric transcyclopalladation (up to 78 % ee). The (R)‐N‐acetylphenylalanine mediated palladation methodology was applicable also to the corresponding N,N‐diethyl (82 % ee, 39 % yield) and pyrrolidinyl (>98 % ee, 43 % yield) cobalt sandwich complexes. A combination of 5 mol % of the latter [(S_p)‐Pyrr‐CAP‐Cl] and AgNO₃ (3.8 equiv) is a catalyst for the allylic imidate rearrangement of an (E)‐N‐aryltrifluoroacetimidate (up to 83 % ee), and this catalyst system is also applicable to the rearrangement of a range of (E)‐trichloroacetimidates (up to 99 % ee). This asymmetric efficiency combined with the simplicity of catalyst synthesis provides accessible solutions to the generation of non‐racemic allylic amine derivatives.     

Enantioselective Reduction of Prochiral Ketones with NaBH4/Me2SO4/(S)-Me-CBS

The enantioselective reduction of prochiral ketones with NaBH₄/Me₂SO₄/(S)-Me-CBS is described. Borane is generated in situ via the reaction of NaBH₄ with Me₂SO₄ in tetrahydrofuran, which is as efficient as the commercial one. Such in situ–generated borane reagent was applied to reduce prochiral ketones in the presence of chiral oxazaborolidine catalyst directly. The corresponding chiral secondary alcohols were obtained with excellent enantiomeric excesses (93–99% ee) and good to excellent yield (80–99%).     

Enantioselective Synthesis of Chiral Isotopomers of 1‐Alkanols by a ZACA–Cu‐Catalyzed Cross‐Coupling Protocol

Chiral compounds arising from the replacement of hydrogen atoms by deuterium are very important in organic chemistry and biochemistry. Some of these chiral compounds have a non‐measurable specific rotation, owing to very small differences between the isotopomeric groups, and exhibit cryptochirality. This particular class of compounds is difficult to synthesize and characterize. Herein, we present a catalytic and highly enantioselective conversion of terminal alkenes to various β and more remote chiral isotopomers of 1‐alkanols, with ≥99 % enantiomeric excess (ee), by the Zr‐catalyzed asymmetric carboalumination of alkenes (ZACA) and Cu‐catalyzed cross‐coupling reactions. ZACA‐in situ iodinolysis of allyl alcohol and ZACA‐in situ oxidation of TBS‐protected ω‐alkene‐1‐ols protocols were applied to the synthesis of both (R)‐ and (S)‐difunctional intermediates with 80–90 % ee. These intermediates were readily purified to provide enantiomerically pure (≥99 % ee) compounds by lipase‐catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of various chiral isotopomers of 1‐alkanols in excellent enantiomeric purity (≥99 % ee) by introducing deuterium‐labeled groups by Cu‐catalyzed cross‐coupling reactions without epimerization.     

Catalytic enantioselective addition of diethylzinc to (hetero)aromatic aldehydes

The asymmetric alkylation with diethylzinc of five heterocyclic aldehydes and benzaldehyde (for comparison) has been studied in the presence of two optically active amino alcohols: (S)-2-amino-1-butanol (AB) and (1S,2R)-N,N-dibutylnorephedrine (DBNE). A number of chiral (hetero)aromatic secondary alcohols were synthesized in high yields (95–98%) with enantioselectivity up to 92% enantiomeric excess (ee) in the presence of DBNE catalyst. Optically active thienyl and 4-pyridyl derivatives were prepared for the first time by catalytic asymmetric alkylation. The influence of the amount of DBNE on the enantioselectivity was investigated. In contrast to benzaldehyde, 2-furan- and 2-thiophene-carbaldehydes, in the case of 3- and 4-pyridinecarbaldehydes the ee values depend directly on the catalyst concentration. © 1998 John Wiley & Sons, Ltd.     

Preparative Asymmetric Reduction of 3-Ketobutyrate and -valerate by Suspended Cells of Thermophilic Bacteria (Thermoanaerobium brockii) in Ordinary Laboratory Equipment

The thermophilic and anaerobic bacteria specified in the title are isolated on a 0.8 kg scale by tangential flow filtration and centrifugation from a 300-1 bioreactor. The microorganisms are stored in a freezer (?20°) and used, analogously to baker's yeast, for asymmetric reductions. Thus, ethyl 3-ketovalerate (4.3) g/1 (H₂O) is converted in 40% yield to (S)-3-hydroxyvalerate ( 6 ), with an enantiomeric excess of 93% (24 h at 72°).     

Novel catalysts for the enantioselective Henry reaction

Two novel catalytic systems based on the Cu^II complexes with N-(3,5-dibromo-2-hydroxybenzyl)- and N-(2-hydroxy-3-nitrobenzyl)-(S)-α,α-diphenylprolinols were developed. These systems catalyze the condensation of 4-nitrobenzaldehyde with nitromethane to produce S-nitroaldol with maximum enantiomeric excess of >90% (99% yield). The reactions of nitromethane with aliphatic aldehydes give the corresponding products in the yields above 80% and ee > 90%.     

Large Scale Bioprocess for the Production of Optically Pure <Emphasis Type="Italic">L</Emphasis>-Carnitine

Summary. A competitive production method using the biotransformation of 4-butyrobetaine to enantiomerically pure L-carnitine was developed and scaled-up by Lonza. The process produces L-carnitine in 99.5% yield, and >99.9% enantiomeric excess (ee). Continuous and discontinuous processes were developed but the fed-batch process was found to be economically the most favourable process mode.     

Nonlinear Effects in Asymmetric Synthesis and Stereoselective Reactions: Ten Years of Investigation

Who would have thought before 1986 that an enantiomerically impure catalyst could give a product in an asymmetric synthesis with an enantiomeric excess higher than that of the catalyst? Until then it was assumed that the ee value of the product (ee_prod) from an asymmetric synthesis was linearly correlated to the ee value of the chiral auxiliary (ee_aux)—in fact a large deviation is possible (see diagram). These nonlinear effects are not only of academic interest since they have a variety of practical uses, which are highlighted in this review.     

A convenient stereoselective synthesis of 5-hydroxy-3-oxoesters and 3-hydroxy-5-oxoesters

A biocatalytic approach was employed for the asymmetric reduction of sterically demanding ketones to prepare 3-hydroxy-5-oxo-5-phenylpentanoates and 5-hydroxy-3-oxo-5-phenylpentanoates. Screening a collection of microorganisms led to the identification of stereocomplementary microbial strains that provide access to both enantiomers of 3-hydroxy-5-oxo-5-phenylpentanoates and 5-hydroxy-3-oxo-5-phenylpentanoates with high enantiomeric excess (up to 99% ee). Moreover, the application of Saccharomyces cerevisiae gave two diastereomers of 3,5-dihydroxy-5-phenylpentanoates with high enantiomeric excess (up to 99% ee). The applicability of the identified strains was demonstrated by transforming the obtained dihydroxy ester into the chemically valuable lactone (4S,6R)-tetrahydro-4-hydroxy-6-phenyl-pyran-2-one.