Doubly diastereoselective conjugate additions of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to enantiopure ε-O-protected α,β-unsaturated esters derived from d-ribose

Enantiopure ε-O-silyloxy- and ε-O-benzyloxy-α,β-unsaturated esters derived from d-ribose, each containing a cis-dioxolane unit, display excellent (⩾95:5 dr) levels of diastereofacial directing ability upon conjugate addition of achiral lithium N-benzyl-N-isopropylamide. In contrast to the corresponding enantiopure ε-O-silyloxy-α,β-unsaturated ester derived from l-tartaric acid, which contains a trans-dioxolane unit, the conjugate additions of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to its cis-configured counterpart result in doubly diastereoselective ‘matched’ and ‘mismatched’ reaction pairings in which the inherent reagent control serves to augment or oppose, respectively, the established substrate diastereocontrol.     

On the properties of the anions derived from α-deprotonation of α-(o-carboran-1-yl)- and α-ferrocenyl-1-alkylbenzotriazoles

The synthesis of 1-[(2-R-o-carboran-1-yl)methyl]benzotriazoles (R = Me, Ph) is described. α-Deprotonation of these compounds followed by reactions of the generated carbanions with MeI give the corresponding α-methylated products. Even at room temperature, they exist in solution as an equilibrium mixture of two conformers due to steric crowding around the C^α atom. In contrast, the anions generated by deprotonation of α-ferrocenyl derivatives of 1-methyl- and 1-ethylbenzotriazoles are ambident and are attacked by electrophiles at both the C^α and N(3) atoms.     

1,3-Dipolar cycloaddition of a nitrone derived from (S)-malic acid to α,β-unsaturated δ-lactones

1,3-Dipolar cycloaddition of nitrone 7 to α,β-unsaturated δ-lactones: non-chiral 2, racemic mixture 3/3ent, d-glycero 3 and d-threo 15 proceeds with high stereoselectivity in the case of 2 and 15, and with a significant kinetic resolution in the case of the racemate 3/3ent. The endo approach of reactants was not observed. CD-spectroscopy proved an attractive tool for determination of the absolute configuration of cycloadducts.     

Enantiomerically pure chiral pyridino-crown ethers: synthesis and enantioselectivity toward the enantiomers of α-(1-naphthyl)ethylammonium perchlorate

Seven new enantiomerically pure chiral pyridino-crown ethers (S,S)-4–(R,R)-10 were prepared. Three of them [(S,S)-4, (S,S)-7 and (R,R)-10] contain one, and two of them [(S,S)-5 and (S,S)-8] contain two linker chains with a terminal double bond. These linker chains were connected to the carbon atom at position 9 (opposite the pyridine moiety) of the macrocycle. The terminal double bond of the linker makes it possible to attach these ligands to silica gel to obtain chiral stationary phases (CSPs). The enantioselectivity of the new ligands toward the enantiomers of α-(1-naphthyl)ethylammonium perchlorate (NEA) was also determined by a titration ¹H NMR method.     

Diastereoselective hydrogenation of α,β-unsaturated but-2-enamides to access the chiral 3-(p-tolyl) butanoic acids

An alternative methodology for the synthesis of chiral 3-(p-tolyl) butanoic acids is presented. This was accomplished through the diastereoselective hydrogenation reaction of different chiral N-3-(p-tolyl) but-2-enamides, using Pd/C in EtOH, to produce the corresponding chiral N-3-(p-tolyl) butanamides with high chemical yields and moderate diastereomeric ratios. Removal of the chiral auxiliary from N-3-(p-tolyl) butanamides gave the respective enantiomerically pure acids.     

Highly enantioselective asymmetric hydrogenation of (E)-β,β-disubstituted α,β-unsaturated Weinreb amides catalyzed by Ir(I) complexes of SpinPhox ligands

The Ir(I) complexes of chiral spiro phosphino-oxazoline ligands (SpinPhox) have demonstrated good to excellent enantioselectivity in the asymmetric hydrogenation (AH) of a variety of (E)-β,β-disubstituted α,β-unsaturated N-methoxy-N-methylamides, affording the corresponding optically active Weinreb amides with up to 97% ee.     

Synthesis of β-carbolines from aldehydes and ketones via the α-siloxy α,β-unsaturated esters

We report an efficient method for the synthesis of β-carbolines from α-siloxy α,β-unsaturated esters, which are accessible from a variety of aldehydes and ketones.     

A novel application of the chiral reagent (s)-2-N-(N′benzylprolyl)-aminobenzaldehyde: Synthesis of optically pure α-methylvaline and α-methylglutamic acid

The synthesis of -methyl substituted amino acids using Ni(II) complexes of the Schiff base obtained from alanine and (S)-2-N-(N'-benzylpropyl)amino-benzaldehyde is described. This complex was alkylated with isopropyl bromide, gramine iodomethylate, and methyl acrylate (in a Michael reaction). From the resulting mixtures of products, diastereomerically pure complexes were obtained by crystallization or silica gel chromatography. Both (S)- and (R)-enantiomers of the optically active amino acids -Me-Val and -Me-Glu were obtained after decomposing the diastereomerically pure complexes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1536–1542, July, 1991.     

Design of chiral bis-phosphoric acid catalyst derived from (R)-3,3'-di(2-hydroxy-3-arylphenyl)binaphthol: catalytic enantioselective Diels-Alder reaction of α,β-unsaturated aldehydes with amidodienes

Chiral bis-phosphoric acid 1 was designed to identify a new class of structural features in chiral Br?nsted acid catalysts. X-ray diffraction analysis revealed the single atropisomer 1, bearing S axial chirality at 3,3'-biaryl substituents on (R)-binaphthyl and intramolecular hydrogen bonding between the two phosphoric acid moieties. The newly designed bis-phosphoric acid 1 was evaluated in the Diels-Alder reaction of α,β-unsaturated aldehydes 4 with 1-N-acylamino-1,3-butadienes 3. After systematic variation of the catalyst substituents, as well as the N-acyl substituents of 1,3-butadiene, the use of an N-Cbz amidodiene 3a in the presence of bis-phosphoric acid 1e with a 2,4,6-tri-isopropylphenyl group was found to be optimal to yield the 1S,6R enantiomeric product 5aa in a Diels-Alder reaction of acrolein (4a). Application of this method to substituted substrates was found to be an efficient approach to the enantioselective synthesis of 3- and 3,6-substituted cyclic formylcarbamates 5. The specific character as well as the utility of 1e was further established by comparing its enantioselectivity, absolute stereochemistry, and catalytic efficiency with those of mono-phosphoric acid 2.     

Application of phosphorylated reagents derived from N,N′-di-[(S)-α-phenylethyl]-cyclohexane-1,2-diamines in the determination of the enantiomeric purity of chiral alcohols

The synthesis of two new N-[(S)-α-phenylethyl] substituted P-chloro-1,3-diazaphospholidines derived from C₂-symmetric trans-1,2-diaminocyclohexanes, and their application as chiral derivatizing agents in the determination of enantiomeric purities of chiral alcohols by means of ³¹P NMR spectroscopy is described.     

γ-Alkylation of α′-(phenylsulfonyl)-α,β-unsaturated ketones: The trianion imperative

γ-alkylation of the title compounds with primary alkyl iodides is possible only when both α′-protons are first ionized with excess lithium diisoproylamide.     

Synthesis of 1-(3-(1,2,4-triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranosyl)uracils via an α,β-unsaturated aldehydrohexose

Summary Mercuric catalyzed hydrolysis of acetylatedL-rhamnal1 gave the ,-unsaturated aldehyde2. 1,2,4-Triazole was coupled, in a Michael type addition reaction, to2 at C-3 in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give, after acetylation at the anomeric center, an anomeric mixture of 1,5-di-O-acetyl-3-(1,2,4-triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranose (3). Reaction of3 with silylated 2,4-dihydroxypyrimidines4 in the presence of trimethylsilyl triflate as catalyst followed by deprotection with 33% methylamine in absolute ethanol afforded the corresponding nucleosides7 and8.

---

Synthese von 1-(3-(1,2,4-Triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranosyl)uracilen über eine ,-ungesättigte Aldohexose

Zusammenfassung Die quecksilberkatalysierte Hydrolyse von acetyliertemL-Rhamnal1 ergab die ,-ungesättigten Aldehyde2. 1,2,3-Triazol wurde in Gegenwart von 1,8-Diazabicyclo[5.4.0]-7-undecen mittels einer Addition vom Michael-Typ an C-3 von2 gekoppelt und ergab dann nach Acetylierung am anomeren Zentrum eine anomere Mischung von 1,5-Di-O-acetyl-3-(1,2,4-triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranose (3). Die Reaktion von3 mit silyliertem 2,4-Di-hydroxypyrimidinen4 in Gegenwart von Trimethylsilyltriflat in absolutem Ethanol ergab die entsprechenden Nucleoside7 und8.

     

Time-resolved photoelectron studies of the relaxation of the S1(1E′') excited state of sym-triazine

We present photoelectron spectra of the lowest singlet state (¹E′') of sym-triazine obtained with 2 ns and 5 ps excitation sources. Comparisons of picosecond and nanosecond spectra are made at three wavelengths, corresponding to the 6₀¹, 6₀² and the 6₀¹12₀¹ vibrational levels. The spectra show that rapid (</ 5 ps) relaxation to the lowest triplet state occurs subsequent to singlet excitation. Coupling of S₁ levels to the T₁ manifold is very inhomogeneous with intersystem crossing rates ranging from 10⁷ s⁻¹ to > 10¹¹ s⁻¹. Furthermore, for excitation at the 6₀¹12₀¹ level we find evidence for relaxation to another excited state at rates ⩾ 10¹¹ s⁻¹.     

Dynamic kinetic resolution of racemic N-phthalyl amino acids using (S)-α-methylpantolactone as the chiral auxiliary

A dynamic kinetic resolution of racemic N-phthalyl amino acids by stereoselective esterification was examined using (S)-α-methylpantolactone as the chiral auxiliary. The reaction of various racemic N-phthalyl amino acids with this chiral alcohol in the presence of both DCC and DMAP afforded predominantly the (S,S)-esters in nearly quantitative yield.     

Deracemisation of α-amino acids—(R)- and (S)-phenylalanine from the same enantiomer of a homochiral auxiliary

Chiral auxiliary (3S)-N,N′-bis-(p-methoxybenzyl)-3-isopropylpiperazine-2,5-dione 1 was employed for the synthesis of both enantiomers of phenylalanine using a regioselective deprotonation/stereoselective reprotonation strategy. Modification of this approach enables the efficient deracemisation of (±)-phenylalanine.     

Synthesis and characterization of chiral di(N-protected-α-amino)diazo-β-diketones from α-diazoketones and imidazolides derived from amino acids

Di(N-protected-α-amino)diazo-β-diketones were prepared by the reaction of activated N-protected-α-amino acids (imidazolides) with α-diazoketones, derived from natural amino acids, in the presence of lithium diisopropylamide in tetrahydrofuran as the solvent at ?78 °C.     

Asymmetric synthesis of (S)- and (R)-α-methylserine based on the chiral recyclable reagent (S)-N-(2-benzoyl-phenyl)-1-benzylpyrrolidine-2-carboxamide

Both enantiomers of -methylserine were synthesized with the use of Ni^II complexes based on the chiral recyclable reagent (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide. Intermediate diastereomeric complexes were separated by crystallization of their O-acetyl derivatives.     

Synthesis and crystal structure of a novel chiral compound prepared from (-)-borneol as a natural chiral auxiliary

Ｒｅｃｅｎｔｌｙ,ｍｕｃｈｅｆｆｏｒｔｈａｓｂｅｅｎｍａｄｅｉｎｔｈｅｄｅｖｅｌｏｐｍｅｎｔｏｆｇｅｎｅｒａｌｌｙａｐｐｌｉｃａｂｌｅｏｒｇａｎｉｃｓｙｎｔｈｅｓｉｓｏｆ5ｈｙｄｒｏｘｙ2(5Ｈ)ｆｕｒａｎｏｎｅ1ｄｕｅｔｏｉｔｓｅｓｓｅｎｔｉａｌｓｔｒｕｃｔｕｒｅｅｎｔｉｔｙｉｎｔｈｅｓｙｎｔｈｅｓｉｓｏｆｓｏｍｅｂｉｏｌｏｇｉｃａｌｌｙａｃｔｉｖｅｎａｔｕｒａｌｐｒｏｄｕｃｔｓａｎｄｉｔｓａｐｐｌｉｃａｔｉｏｎａｓａｕｓｅｆｕｌｉｎｔｅｒｍｅｄｉａｔｅｉｎｏｒｇａｎｉｃｓｙｎｔｈｅｓｉｓ[1—3].Ｃｏ…     

Halo-substituted (S)-N-(2-benzoylphenyl)-1-benzylpyrolidine-2-carboxamides as new chiral auxiliaries for the asymmetric synthesis of (S)-α-amino acids

The synthesis of new chiral auxiliaries (S)-N-(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)-pyrrolidine-2-carboxamide (1a), (S)-N-(2-benzoylphenyl)-1-(pentafluorobenzyl)pyrrolidine-2-carboxamide (1b), and (S)-N-(2-benzoylphenyl)-1-(4-isopropoxytetrafluorobenzyl)pyrrolidine-2-carboxamide (1c) and their application in the asymmetric synthesis of amino acids using Ni^II complexes of their Schiff"s bases with alanine and glycine are described. Compound 1a is particularly appropriate for highly stereoselective synthesis of -methyl--amino acids with high enatiomeric purity (ee >95%).     

Enantioselective syntheses of α-phenylalkanamines via intermediate addition of Grignard reagents to chiral hydrazones derived from (R)-(−)-2-aminobutan-1-ol

The hydrazine (R)-(−)-28 was obtained in four steps from 2-aminobutan-1-ol (R)-(−)-11, and reacted with benzaldehyde to give the hydrazone (R)-(−)-29. Nucleophilic addition of various alkyl Grignard reagents to the latter yielded the corresponding trisubstituted hydrazines (R,R)-30a–g in 70–89% yields and having d.e.s=100% (¹H and ¹³C NMR). Catalytic hydrogenolysis of these hydrazines afforded the corresponding (R)-(+)-α-phenylalkanamines (R)-(+)-31a–g having e.e.s=90–92% (chiral GPC).