Enantiopure Methyl Research Articles

Ground-State Photoelectron Circular Dichroism of Methyl p-Tolyl Sulfoxide by Single-Photon Ionisation from a Table-Top Source.

Single-photon ionisation of enantiopure methyl p-tolyl sulfoxide by circularly polarised light at 133 nm shows remarkably strong photoelectron circular dichroism (PECD), which has been measured in a velocity-map-imaging spectrometer. Both enantiomers were measured, each showing a PECD of a similar magnitude (ca. 25 %). These experiments were carried out with a tabletop high-harmonic source with a photon energy of 9.3 eV, capable of ionising the electronic ground state of most organic and inorganic molecules. Ab-initio scattering calculations provide a theoretical value of the expected chiral asymmetry parameter, and agree very well with the measured values once orbital mixing via configuration interaction in the cation is taken into account. This study demonstrates a simple photoionisation scheme that can be readily applied to study the time-resolved PECD of photochemical reactions and suggests a pronounced sensitivity of PECD to electronic configuration interaction in the cation.

Enantiopure Methyl- and Phenyllithium: Mixed (Carb-)Anionic Anisyl Fencholate-Aggregates

Methyl- and phenyllithium aggregates with enantiopure anisyl fencholate units form after reaction of organolithium reagent with (+)-anisyl fenchol in hydrocarbon and some ethereal solvents. These carbanionic aggregates are characterized by X-ray crystal analyses and exhibit both 3:1 stoichiometry and distorted cubic Li4O3C1 cores, in which three lithium ions coordinate the carbanion (i.e., methylide or phenylide). These three lithium ions define a Lewis acidic surface (Li3), binding the carbanion and expanding with the steric demand of the carbanion (i.e., from Me: 2.62 A2, over n-Bu: 2.65 A2 (previous work) to Ph: 2.79 A2). Methylation and phenylation reactions of various prochiral aldehydes employing these methyllithium and phenyllithium aggregates yield alcohols with up to 44% ee. To rationalize the formation of the mixed (carb-)anionic aggregates, aggregate formation energies, describing co-condensations of RLi (R = Me, Ph, n-Bu) and lithium fencholates, are computed for the 3:1 and 2:2 stoichiometrie...

ChemInform Abstract: Stereocontrolled Transformation of Nitrohexofuranoses into Cyclopentylamines via 2‐Oxabicyclo[2.2.1]heptanes. Part 6. Synthesis and Incorporation into Peptides of the First Reported 2,3‐Dihydroxycyclopentanecarboxylic Acid.

Herein we report the intramolecular alkylation of nitronates of methyl-5-O-benzyl-3,6-deoxy-6-nitro-β-d-glucofuranoside and methyl-5-O-benzyl-3,6-deoxy-6-nitro-α-d-glucofuranoside into the corresponding 2-oxabicyclo[2.2.1]heptane derivatives. Similarly, methyl-3-O-benzyl-5-deoxy-5-nitromethyl-β-d-xylofuranoside and methyl-3-O-benzyl-5-deoxy-5-nitromethyl-α-d-xylofuranoside were cyclized to (1R,3R,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane and (1R,3S,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane, respectively. These 2-oxabicyclo[2.2.1]heptane derivatives were eventually transformed into enantiopure methyl (1S,2S,3R,4S,5R)-2-amino-2,3- dihydroxycyclopentanecarboxylate and this novel β-amino acid was incorporated into peptides. © 2014 Elsevier Ltd. All rights reserved.

Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. Part 6: synthesis and incorporation into peptides of the first reported 2,3-dihydroxycyclopentanecarboxylic acid

Herein we report the intramolecular alkylation of nitronates of methyl-5-O-benzyl-3,6-deoxy-6-nitro-β-d-glucofuranoside and methyl-5-O-benzyl-3,6-deoxy-6-nitro-α-d-glucofuranoside into the corresponding 2-oxabicyclo[2.2.1]heptane derivatives. Similarly, methyl-3-O-benzyl-5-deoxy-5-nitromethyl-β-d-xylofuranoside and methyl-3-O-benzyl-5-deoxy-5-nitromethyl-α-d-xylofuranoside were cyclized to (1R,3R,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane and (1R,3S,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane, respectively. These 2-oxabicyclo[2.2.1]heptane derivatives were eventually transformed into enantiopure methyl (1S,2S,3R,4S,5R)-2-amino-2,3-dihydroxycyclopentanecarboxylate and this novel β-amino acid was incorporated into peptides.

Chiral para-alkyl phenyl ethers of glycerol: synthesis and testing of chirality driven crystallization, liquid crystal, and gelating properties

A series of enantiopure and racemic p-alkylphenyl glycerol ethers 1a–k were synthesized. A new, sensitive, and pictorial method of comparison of the IR spectra of solid enantiopure and racemic samples was developed to obtain preliminary information on the crystallization types of these compounds. In order to detect the subtle differences in the organization of the chiral solid phase, a new easily implemented approach, based on a chromatographic measuring of the relative abundance of the enantiomers in a single solution in equilibrium with a solid sample of arbitrary (0<ee<1) composition, is reported. One new conglomerate compound (Alk=n-Pr) and one borderline case (Alk=n-Bu) are disclosed. Higher members of the series of 1 (starting with an n-Bu derivative) are turned into liquid crystals upon melting; no significant differences between racemic and non-racemic samples were found. Only enantiopure methyl-, n-butyl, n-pentyl, n-hexyl, and n-heptyl substituted 1 were able to form supramolecular gels in hydrocarbon solvents; all racemic ethers 1 did not show such ability.

Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. Part VI: Synthesis and incorporation of the novel polyhydroxylated 5-aminocyclopent-1-enecarboxylic acids into peptides

The first total synthesis of enantiopure methyl (3a R,4 S,5 S,6 R,6a S)-4-benzyloxycarbonylamino-6-hydroxy-2,2-dimethyl-tetrahydro-3a H-cyclopenta[ d][1,3]dioxole-5-carboxylate has been carried out according to our recent novel strategy for the transformation of nitrohexofuranoses into cyclopentylamines. This approach is based on an intramolecular cyclization that leads to 2-oxabicyclo[2.2.1]heptane derivatives. E1cb elimination of the methoxy substituent was observed when attempting to incorporate these β-amino acid into peptides. As a result, the synthesis and incorporation of the first polyhydroxylated 5-aminocyclopent-1-enecarboxylic acid into peptides were developed.

ChemInform Abstract: Two Practical and Efficient Approaches to Fluorinated and Nonfluorinated Chiral β-Imino Sulfoxides.

Reaction of fluorinated and nonfluorinated N-substituted imidoyl chlorides 1 with lithium derivatives of enantiopure methyl p-tolyl sulfoxide 2a (or racemic methyl phenyl sulfoxide 2b) gave a wide variety of chiral N-substituted β-imino sulfoxides 4 in good to excellent yields. The title compounds (R)-4 were also prepared by aza-Wittig reaction of γ-fluoro-β-keto sulfoxides (R)-5 and N-aryl iminophosphoranes 6. The imino−enamino equilibrium was studied, showing, in all instances, the imino form as the predominant tautomer independent of the nature of the N-substituent. The configuration of the CN double bond was found to be Z for both N-alkyl and N-aryl derivatives on the basis of 1H NMR NOE difference experiments performed over several compounds. Ab initio calculations (HF/6-31G*) carried out on several representative examples of 1 and 4 are, in general, consistent with the experimental results.

Studies on the stereocontrolled transformation of nitrohexofuranoses into 2-oxabicyclo[2.2.1]heptanes. V: Synthesis of enantiopure methyl (1 R,2 R,4 S)-2-amino-4-hydroxycyclopentanecarboxylate

The first total synthesis of enantiopure methyl (1 R,2 R,4 S)-2-amino-4-hydroxycyclopentanecarboxylate was carried out according to our recent novel strategy for the transformation of nitrohexofuranoses into cyclopentylamines, which is based on an intramolecular cyclisation leading to 2-oxabicyclo[2.2.1]heptane derivatives. It was observed that one of the substrate anomers produces an elimination rather than a cyclisation reaction. These and other differences in the reaction paths for this key step were rationalised by means of molecular mechanism based calculations.

Racemic β‐Sheets as Templates for the Generation of Homochiral (Isotactic) Peptides from Aqueous Solutions of (RS)‐Valine or ‐Leucine N‐Carboxy‐ anhydrides: Relevance to Biochirogenesis

As part of our program on biochirogenesis of homochiral peptides from racemic precursors, we report the feasibility of obtaining peptides with homochiral sequences composed of up to 25 residues of the same handedness in the polymerization of racemic valine or leucine N-carboxyanhydrides in aqueous solutions, as initiated by amines. The composition of the oligopeptides was determined by MALDI-TOF mass spectrometry, and the sequences of some of the heterochiral diastereoisomers were studied by MALDI-TOF MS/MS performed on samples in which the S enantiomers of the monomer were tagged with deuterium atoms. The process comprises several steps: 1) a Markov mechanism of asymmetric induction in the early stages of the polymerization yields libraries of racemic oligopeptides enriched with isotactic diastereoisomers, together with oligopeptide sequences containing enantiomeric blocks of homochiral residues; 2) the short peptides self-assemble into racemic colloidal architectures that serve as regio-enantioselective templates in the ensuing process of chain elongation; 3) homochiral residues of the amino acids located at the periphery of these colloidal aggregates exert efficient enantioselection, which results in the formation of long isotactic oligopeptides. The final diastereoisomeric distribution of the peptides depends upon the composition of the templates, which is determined by the concentration of the initiator. The racemic mixtures of isotactic peptides can be desymmetrized by using enantiopure methyl esters of alpha-amino acids as initiators.

Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. III: synthesis of enantiopure methyl (1 S,2 S,3 R,4 S,5 R)-2-amino-3,4,5-trihydroxycyclopentanecarboxylate

The first total synthesis of enantiopure methyl (1 S,2 S,3 R,4 S,5 R)-2-amino-3,4,5-trihydroxycyclopentanecarboxylate was carried out according to our recent novel strategy for the transformation of nitrohexofuranoses into cyclopentylamines, which is based on an intramolecular cyclization leading to 2-oxabicyclo[2.2.1]heptane derivatives. Differences in reactivity for this key step were rationalized by using molecular mechanism-based calculations.

Simple and Highly Convenient Two-Step Practical Procedure for the Synthesis of Optically Pure MethylD-erythro-2,3-Dihydroxybutanoate

A synthesis of enantiopure methyl D-erythro-2,3-dihydroxybutanoate has been realized using two simple and consecutive reactions on D-erythronolactone as the starting material. The two reactions are lactone ring opening with hydrobromic acid in methanol and subsequent reductive debromination.

New Chiral Synthesis of Methyl and Allyl Disubstituted Butyrolactone: A Formal Synthesis of (-)-Ngaione

A new chiral synthesis of butyrolactone [(-)-7] bearing methyl and allyl substituents at the γ-position has been established via diastereoselective continuous nucleophilic addition to the chiral tricyclic lactone [(-)-1] as the key step. In practice, continuous nucleophilic addition to the tricyclic lactone [(-)-1] by using the combination of methyllithium and allylmagnesium bromide proceeded to yield the corresponding diol (8) diastereoselectively. After oxidation of 8, enantiopure methyl and allyl disubstituted butenolide (10) was obtained via retro-Diels-Alder reaction. Selective 1,4-reduction of 10 afforded the corresponding butyrolactone [(-)-7], which is the key intermediate for (-)-ngaione synthesis.

Enantioselective synthesis of both enantiomers of γ-ionone, γ-damascone, karahana lactone and karahana ether

A straightforward enantioselective synthesis of both enantiomers of the title compounds is described starting from enantiopure methyl (2 S,6 R)- or (2 R,6 S)- cis-2-hydroxy-γ-cyclogeraniate. These versatile building blocks are obtained by biomimetic cyclization of methyl (6 S)- or (6 R)-( Z)-6,7-epoxy-7-methyl-3-(trimethylsilyl)methyl-2-octenoate, respectively. The chiral information was encoded by a highly regioselective Sharpless asymmetric dihydroxylation of the corresponding diene.

A chemoenzymatic approach to the synthesis of enantiomerically pure aza analogues of paraconic acid methyl ester and both enantiomers of methyl β-proline

Enantiopure methyl esters of 1-alkyl-5-oxo-3-pyrrolidinecarboxylic acids were obtained by enzymatic resolution of the corresponding chiral racemic mixtures. A particularly favourable interaction, also supported by molecular mechanics calculations, was observed between the 1-benzyl derivative and α-chymotrypsin, for which the enantiomeric ratio, E, exceeded 200. The absolute configurations of the lactams were determined by means of CD spectroscopy. From the resulting enantiomerically pure (99% e.e.) ( S)-(+)-1-benzyl-3-pyrrolidinecarboxylic acid and methyl ( R)-(−)-1-benzyl-3-pyrrolidinecarboxylate, the methyl esters of (+) and (−)-β-proline were synthesised in 99% e.e. and 18 and 22% overall yield, respectively.

The "Non-Oxidative" pummerer reaction: conclusive evidence for S(N)2-type stereoselectivity, mechanistic insight, and synthesis of enantiopure L-alpha-trifluoromethylthreoninate and D-alpha-trifluoromethyl-allo-threoninate(1)

Enantiopure methyl D-alpha-trifluoromethyl-allo-threoninate 18 and L-alpha-trifluoromethylthreoninate 19 were synthesized using (R)-ethyl p-tolylsulfoxide as chiral alpha-hydroxyethyl anion equivalent. The key step was the S(N)2-type replacement of the sulfinyl auxiliary with a hydroxy group, via trifluoroacetic anhydride promoted "non-oxidative" Pummerer reaction (NOPR) of the diastereomeric intermediate beta-sulfinyl amines 14 and 15, obtained by condensation of (R)-ethyl p-tolylsulfoxide 13 with the N-Cbz imine of methyl trifluoropyruvate 12. The conclusive evidence for S(N)2-type stereoselectivity of the NOPR was achieved by X-ray diffraction of both the starting diastereomer 14 and the p-bromobenzoate 25, obtained from the threoninate 19. NMR monitoring of the NOPR performed on 15 allowed the detection of a transient intermediate, which was identified as the four membered cyclic sigma-sulfurane 27. This intermediate spontaneously rearranged (40 min, rt) into the corresponding sulfenamide 17, probably via an intramolecular displacement of the sulfinyl by a trifluoroacetoxy group, with inversion of configuration at the carbon stereocenter. The same process occurred for the diastereomeric beta-sulfinyl amine 14, but the sulfenamide 16 was formed at a very fast rate, thus precluding NMR detection of the corresponding sigma-sulfurane intermediate 26. One-pot treatment of the diastereomeric sulfenamides 16 and 17 with NaBH(4) afforded very good yields of the corresponding threoninates 18 and 19.

Two Practical and Efficient Approaches to Fluorinated and Nonfluorinated Chiral beta-Imino Sulfoxides.

Reaction of fluorinated and nonfluorinated N-substituted imidoyl chlorides 1 with lithium derivatives of enantiopure methyl p-tolyl sulfoxide 2a (or racemic methyl phenyl sulfoxide 2b) gave a wide variety of chiral N-substituted beta-imino sulfoxides 4 in good to excellent yields. The title compounds (R)-4 were also prepared by aza-Wittig reaction of gamma-fluoro-beta-keto sulfoxides (R)-5 and N-aryl iminophosphoranes 6. The imino-enamino equilibrium was studied, showing, in all instances, the imino form as the predominant tautomer independent of the nature of the N-substituent. The configuration of the C=N double bond was found to be Z for both N-alkyl and N-aryl derivatives on the basis of (1)H NMR NOE difference experiments performed over several compounds. Ab initio calculations (HF/6-31G) carried out on several representative examples of 1 and 4 are, in general, consistent with the experimental results.

ChemInform Abstract: Convenient Preparations of Racemic and Enantiopure Methyl 6‐ Oxopipecolate.

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Convenient Preparations of Racemic and Enantiopure Methyl 6-Oxopipecolate

Convenient Preparations of Racemic and Enantiopure Methyl 6-Oxopipecolate

Convenient preparations of racemic and enantiopure methyl 6-oxopipecolate

Short, convenient syntheses of racemic and enantiopure methyl 6-oxopipecolate are described, starting from either pipecolic acid or (S)-lysine respectively. The sequence for the latter compound relies upon improved methodology for the oxidation of C-6 of lysine.