Moderate Diastereomeric Excesses Research Articles

Remote steric effects of C2-symmetric planar-chiral terpyridine ligands on copper-catalyzed asymmetric cyclopropanation reactions

A series of enantioselective cyclopropanation reactions of substituted alkenes with diazoacetates was investigated in the presence of Cu(OTf)2 with C2-symmetric planar-chiral bridged 2,2′:6′,2″-terpyridines. Planar-chiral terpyridine–copper complexes exhibited moderate diastereomeric excesses with good enantioselectivities of cis-cyclopropane products in catalytic asymmetric cyclopropanation reactions of various styrene derivatives with ethyl diazoacetate. A remote steric effect was found to enhance enantioselectivity for the cyclopropanation induced by a sterically demanding substituent beyond the ansa-bridge of pyridinophane ligands on the other side of the reaction site as a relay of steric influences through flexible cyclophane bridges.

Expanding the Scope of Alcohol Dehydrogenases towards Bulkier Substrates: Stereo‐ and Enantiopreference for α,α‐Dihalogenated Ketones

AbstractAlcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding α,α‐dihalogenated ketones, obtaining optically pure β,β‐dichloro‐ or β,β‐dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH‐A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic α‐substituted ketones, namely α‐bromo‐ α‐chloro‐ and α‐chloro‐α‐fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)‐enantiomer was obtained by using ADH‐A, although with moderate diastereomeric excess (>99 % ee, 63 % de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45 % de).

Oxidising agent and catalyst chirality effect on epoxidation of R-(+)- Limonene using Jacobsen-type catalysts

The oxidising agent effect on R-(+)-Limonene epoxide diastereoselectivity using chiral and achiral Jacobsen’s type catalysts is presented. The type of oxidising agent strongly influences diastereoselectivity. Moderate diastereomeric excesses were achieved in the presence of oxidising agents prepared in situ but in the absence of catalyst (23% for DMD and 29% for O2/pivalaldehyde). Similar diastereomeric excesses were obtained with both chiral and achiral catalyst when the oxidising agents were prepared in situ; 56% and 50% excesses were obtained when using DMD for the chiral and achiral catalyst (respectively) and 38% using O2/pivalaldehyde for both catalysts. Diastereomeric excesses were not observed in the absence of catalyst when using commercial oxidising agents; the chiral catalyst presented larger diastereomeric excesses than its achiral counterpart: 65% and 38% excess using NaOCl for the chiral and achiral catalyst, respectively, and 79% and 39% using m-CPBA for the chiral and achiral catalyst, respectively. This suggests that at least one oxidant species, different from the conventionally accepted (MnV(oxo)), might be involved in this catalytic process. A modification of the traditional catalytic cycle is proposed considering the type of oxidising agent. The catalyst’s chiral centre appears to govern asymmetric induction when commercial oxidising agents are used, whereas the R-(+)-Limonene chiral centre appears to govern asymmetric induction in the presence of in situ-prepared oxidising agents. On the other hand, the chemical stability of Jacobsen’s catalyst improved when in situ produced DMD was used as oxidising agent.

Polar Hetero-Diels−Alder Reactions of 4-Alkenylthiazoles with 1,2,4-Triazoline-3,5-diones: An Experimental and Computational Study

The hetero-Diels-Alder reactions of 4-alkenylthiazoles with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) lead to new heteropolycyclic systems in excellent yields and high levels of stereocontrol through an exclusively suprafacial approach. 4-Alkenylthiazoles with a stereogenic center placed at the alkenylic substituent react with PTAD giving the corresponding chiral cycloadducts in moderate diastereomeric excesses. The stereochemical course is dominated by the steric interactions at the two diastereomeric transition states. A computational study of these processes with structurally simpler reagents has been carried out. A concerted pathway via a highly asynchronous transition state is preferred for 2-unsubstituted 4-vinyl and 4-styrylthiazoles. However, two alternative and equally likely pathways, concerted and stepwise, have been found to be followed by 2-methyl- or 2-phenyl-substituted 4-styrylthiazoles. The concerted pathway features a highly asynchronous transition state. For the stepwise pathway, the rate-determining step is the first one, as the energy barrier for the second step is virtually nonexistent.

Stereoselective oxidation of linalool with tert-butyl hydroperoxide, catalyzed by a vanadium(V) complex with a chiral terpenoid ligand

Stereoselective epoxidation of (−)-( R)-linalool by tert-butylhydroperoxide (TBHP) catalyzed by a vanadium(V) complex formed by interaction of [VO(acac) 2] or [VO(O n-Bu) 3] with a new chiral terpenoid ligand (L) is reported. Moderate diastereomeric excess (de 56%) was attained in toluene at 20 °C. 51 V , 13 C and 17 O NMR spectroscopic monitoring of the studied catalytic system showed that a new complex 1 forms quantitatively upon interaction of [VO(O n-Bu) 3] with L in CH 2Cl 2. Compound 1 is a mononuclear complex of vanadium(V), which incorporates the tridentate chiral ligand L, as well as VO moieties. It has been shown that TBHP binds to 1 giving a 1·TBHP adduct with the association constant K=1.36±0.11 l mol −1 at room temperature and enthalpy Δ r H 298 0=−6.5±2.0 kJ mol −1 and entropy Δ r S 298 0=−20±6 J mol −1 K −1. These thermodynamic parameters are typical for outer sphere complexes (OSCs). Adduct 1·TBHP is suggested to be a precursor of the active intermediate of the stereoselective epoxidation process.

Organotransition-metal-modified sugars: Part 17. Glucal-derived carbene complexes: synthesis and diastereoselective benzannulation

The addition of triisopropylsilyl and/or isopropylidene-protected 1-lithio- d-glucals prepared in situ from stannylated precursors 5 and 6 to hexacarbonyl chromium followed by methylation affords d- arabino-hex-1-enopyranosylcarbene complexes 7 and 8. They undergo a diastereoselective benzannulation upon reaction with tolan and 3-hexyne to give polyoxygenated chromans 9 to 12 in good yields and moderate diastereomeric excess values. The conformation of the glucal moiety in the carbene ligand and in the chroman skeleton is controlled by the nature of the protective groups. 1H-NMR studies and single crystal X-ray analyses indicate a 5H 4-conformation of the sugar moiety for the triisopropylsilyl compounds 7, 9a, b, 10a, b and 11 and 4H 5-conformation for the isopropylidene derivatives 8 and 12a– c in solution, and further for 8 and 12a in the solid state.

Diastereoselective and enantioselective heterogeneous catalytic hydrogenation of aminocinnamic acid derivatives

Various kinds of aminocinnamic acid derivatives were hydrogenated with different stereoselectivities. In the presence of cinchonidine or (−)-dihydroapovincaminic acid ethyl ester modifiers, the enantioselective hydrogenations resulted in very low enantiomeric excesses (ee). Moderate diastereomeric excesses (de, 5–68%) were achieved in the diastereoselective hydrogenations. The highest de (68%) was obtained in the hydrogenation of N-acetyldehydrophenylalanyl-( S)-prolinanilide due to a 10-member intermediate stabilized by hydrogen bond.

Addition of cyclopentadiene and 2-trimethylsilyloxyfuran to quinones bearing a menthyl ester chiral auxiliary

Addition of cyclopentadiene to 2-carbomethoxy-1,4-benzoquinone 9 afforded Diels-Alder adduct 10 using the Lewis acids ZnCl 2 and ZnBr 2 whereas the fragmenatation product 11 was the major product when using SnCl 4 and TiCl 4. Addition of cyclopentadiene to 1,4-benzoquinone 8 bearing a menthyl ester at C-2 afforded Diels-alder adduct 12 in moderate diastereomeric excess using ZnCl 2 and ZnBr 2 as Lewis acids. Use of TiCl 4 and SnCl 4 afforded the fragmentation product 13 also in moderate diastereomeric excess. Addition of 2-trimethylsilyloxyfuran to chiral naphthoquinone 4 and benzoquinone 8 afforded furofuran adducts 14 and 15 respectively as a 1:1 mixture of diastereomers.

Diastereoselectivity in the Mukaiyama-Michael Reaction Employing alpha-Acyl beta,gamma-Unsaturated Phosphonates.

The unique electronic and structural nature of the alpha-acylphosphonate functional group affords both dimeric and chelated complexes of diethyl crotonyl phosphonate (1; DECP) with stannic chloride (SnCl(4)). The dimeric complex, SnCl(4).(DECP)(2) (5) results from the coordination of two DECP molecules, ligated via the phosphoryl oxygens to the tin atom. The chelated complex, SnCl(4).(DECP) (6), is best represented with both phosphoryl and carbonyl oxygens coordinated to the metal center. Both metal ligated and chelated complexes have unique (13)C (31)P, and (119)Sn NMR spectra. In complex 5, the (13)C NMR resonances attributed to the carbonyl carbons were shifted upfield of free DECP. A monocoordinating Lewis acid, BF(3).OEt(2), produced a similar chemical shift trend in both the (13)C and (31)P NMR spectra of the BF(3).DECP complex. Essentially quantitative yields and moderate diastereomeric excesses favoring anti (or trans) diethyl 6-phenyl-4,5-dimethyl-6-(trimethylsilyloxy)-2-dihydropyranphosphonate (3) and diethyl 5-phenyl-3,4-dimethyl-1,5-dioxopentanephosphonate (4) were obtained from both chelated and dimeric SnCl(4).(DECP)(n) (n = 1, 2) when treated with either diastereomeric (Z)- or (E)-1-phenyl-1-(trimethylsilyloxy)-1-propene 2. Diethyl crotonylphosphonate (1), 3, and 4 were fully characterized.

Stereocontrolled routes to derivatives of 3-alkoxycarbonyl-2-amino-4-aryl-5-cyano-6-phenyl-4 H-pyrans

The asymmetric Michael addition of cyanoacetates 2b-e and benzoylacetonitrile 6 to α-benzoylcinnamonitrile 3 and α-cyanocinnamates 7b-e, respectively, has been studied. The resulting 3-alkoxycarbonyl-2-amino-4-aryl-5-cyano-6-phenyl-4 H-pyrans 4b-e have been obtained in moderate diastereomeric excess and good chemical yield.

Synthesis of Thioaldehydes Having Optically Active Alkoxy Moiety and Their Asymmetric Hetero Diels-Alder Reaction

Optically active α-alkoxycarbonylthioaldehydes (2a-g) were prepared using 8-arylmenthols as chiral auxiliaries. Their asymmetric hetero Diels-Alder reactions with cyclopentadiene gave the endo cycloadducts (3 and 4) and exo cycloadducts (5 and 6) with moderate diastereomeric excesses. However, the major endo cycloadducts (3b-g) were isolated in optically pure form. This is the first chiral synthesis of 2-thiabicyclo[2.2.1]hept-5-ene ring system. The absolute configuration of the cyclic carbonate (12), which was prepared from the major endo cycloadduct (3c) via the epimerization, or the minor exo compound (6c), was determined as 1R by X-ray analysis. The cycloadduct (3c) was transformed to a potential intermediate (14) for the synthesis of carbocyclic homonucleosides

Chiral 2-acetamidoacrylates in conjugate addition – asymmetric enolate trapping reactions. Asymmetric synthesis of phenylalanine

A new route to the asymmetric synthesis of α-amino acids based on the reactivity of chiral 2-acetamidoacrylates with nucleophiles through a conjugate addition followed by diastereoselective protonation of the enolate is described. Phenylalanine precursors are obtained in excellent chemical yields (80–95%) with moderate diastereomeric excess (0–44%) through the reaction of chiral 2-acetamidoacrylates with phenylmagnesium bromide in the presence of CuI followed by diastereoselective enolate protonation.

Asymmetric synthesis IV. Preparation of chiral α-aminonitriles from a new N-cyanomethyl-1,3-oxazolidine synthon

The synthesis of (−)-N-Cyanomethyl-4-phenyl-1,3-oxazolidine 1 is reported. Good yields and moderate diastereomeric excesses (d.e.s.) of mono- and di-substituted α-aminonitriles were obtained from this simple chiral template.