Synthesis of enantiomerically pure α-amino-β-hydroxy-cyclobutanone derivatives and their transformations into polyfunctional three- and five-membered ring compounds

Ketenes readily cycloadded to (R)-tert-butyldihydrooxazole 2a-d to yield enantiomerically pure bicyclic cyclobutanones. The cycloadditions proceeded with unusual regiochemistry giving predominantly or exclusively protected α-amino-β-hydroxycyclobutanone derivatives. The adducts could be converted into a variety of interesting enantiopure intermediates equipped with many functional groups: α-amino-β-hydroxy cyclopropane carboxylic acid derivatives, α-amino-β-hydroxy succinic acid derivatives, α-amino-β-hydroxy lactones and lactams derivatives.     

Synthesis of new enantiomerically pure β-amino alcohols of the pinane series

A series of new β-amino alcohols with pinane structure, (+)- and (?)-3α-amino-10β-pinan-4β-ols, 4β-amino-10β-pinan-3α-ol, and 4α-amino-10β-pinan-3α-ol have been synthesized with the goal of using them as organocatalysts in the aldol reaction of isatin with acetone.     

Synthesis of enantiomerically pure bicyclic condensed δ-lactones via microbial reduction and enzymic resolution strategies

The formation of enantiopure δ-lactones condensed with alicyclic rings has been achieved either by reduction with baker's yeast of the corresponding δ-keto esters and δ-keto acids or by enzymic resolution of the former compounds. The absolute configurations of the lactones were determined by means of CD spectroscopy, using the correlation method.     

Preparation of enantiomerically pure α-hydroxyl phosphinates via hydrophosphorylation of aldehydes with H-phosphinate

The hydrophosphorylation of aldehydes with a P-stereogenic H-phosphinate was realized by heating two compounds in a neat state or catalyzed by a base, to afford P-retention α-hydroxyl phosphinates. The (S_P,S_C) and other diastereomers were isolated, and their structures were confirmed by NMR spectroscopy and crystallography.     

Stereocontrolled fluorobenzylation of vinyl sulfones and α,β-unsaturated esters mediated by a remote sulfinyl group. Synthesis of functionalized enantiomerically pure benzylic fluorides

A sulfinyl group in an ortho position confers enough chemical and configurational stability to monofluorobenzylcarbanions to evolve in a completely stereoselective way in their reactions with β-substituted vinyl sulfones and α,β-unsaturated esters. Reactions afford easily separable mixtures of two epimers differing in the configuration of the center derived from the Michael acceptor (up to 98% de). They can be easily converted into enantiomerically pure γ-fluorinated γ-phenylsulfones and γ-phenylesters bearing two chiral centers.     

Highly stereoselective reduction of acyclic α-sulfinyl ketimines: synthesis of enantiomerically pure β-aminosulfoxides

The DIBAL reduction of enantiomerically pure α-sulfinyl ketimines can be achieved almost completely stereoselectively under ZnX₂ catalysis, regardless of the alkyl or aryl substituent at nitrogen and the aliphatic (cyclic or acyclic) or aromatic character of the imine. Steric factors as well as the electrophilic character of the hydride are responsible for the stereochemical course of the reduction.     

Nucleophilic opening of chiral bis-aziridines: A route to enantiomerically pure α-amino acids and polysubstituted piperidines

Suitably protected chiral functionalised bis-aziridines, prepared from D-mannitol, are opened by various organometallic reagents (organomagnesium,-lithium and -copper derivatives) as well as by heteronucleophiles (N₃^-, Br^-, Cl^-, HS^-, PhS^-). Orientation of the reaction toward diopening (route to enantiomerically pure α-amino acids) or toward heterocyclisation (route to chiral, polysubstituted piperidines) is influenced, notably, by the nature of the N-protecting group and of the nucleophile and by the presence or not of Lewis acids.     

Synthesis and characterization of α,ω-dichloro-polymethylphenylsilane

The synthesis of a functional polysilane, α,ω-dichloro-polymethylphenylsilane (α,ω-dichloro-PMPS), based on the Wurtz-type reductive coupling, has been considered. A study of some reaction parameters shows that both yield and molecular weight distribution of α,ω-dichloro-PMPS can be greatly influenced by the work-up conditions, reaction time, monomer concentration and temperature during the initiation of the polymerization. By varying the synthesis conditions, different ratios of high and low molecular weight fractions were obtained. Samples of different molecular weight were isolated by fractional precipitation of the crude polymers. The chlorine-end functionalization was confirmed by ²⁹Si NMR spectroscopy and the concentration of end-groups was quantitatively determined by elemental analysis of chlorine.     

Reaction between hydrazines and chiral α-acetylenic ketones: synthesis of novel enantiomerically pure pyrazolyl-β-amino alcohols

A simple and efficient methodology toward the stereoselective synthesis of novel, enantiomerically pure, pyrazolyl-β-amino alcohols is presented. Thus, when hydrazines 4a,b were allowed to react at 0°C with chiral α-acetylenic ketones of type 3, pyrazolyl oxazolidine derivatives 5a–d were formed with total regioselectivity in 92–97% yield. Subsequent oxazolidine ring opening by means of TFA, and re-protection of the amino group as the N-Boc derivatives, afforded enantiopure amino alcohols 7a–d.     

Synthesis of novel and enantiomerically pure epoxypropylamine: a divergent route to the chiral β-adrenergic blocking agents

The chiral building block (S)-N-benzyl-N-isopropyl-2,3-epoxypropylamine is obtained by means of chlorohydroxylation of allylamine, followed by Jacobsen's hydrolytic kinetic resolution with water. A concise, divergent five-step synthesis of three β-adrenergic blocking agents in high enantiomeric excess using (S)-N-benzyl-N-isopropyl-2,3-epoxypropylamine as the key intermediate is described.     

Synthesis of α-alkyl- and α,α-dialkyl-β-phenyltryptamines

A new method was developed for the synthesis of -alkyl- and ,-dialkyl--phenyltryptamines based on alkylation of nitroalkanes with -phenyl-nor-gramine.     

Synthesis of enantiomerically pure carbocyclic 3′-azido-2′, 3′-dideoxythymidine,a potential anti-aids drug

(+)-1-[(1R,3S,4S)-3-Azido-4-(hydroxymethyl)cylopentyl]-5-methyl- 2,4-(1H,3H)-pyrimidindione 7 (C-AZT) was synthesized starting from mesylated compound 1 in a six step sequence via urea derivative 5.     

Synthesis,Characterization, and Structures of α-Substituted Selenenyl-Acetophenones

Abstract

A series of α-substituted selenenyl acetophenone derivatives of the types, [PhC(OCH₂CH₂O)CH₂Se]₂, [PhC(OCH₂CH₂O)CH₂SeR], (PhCOCH₂Se)_2, and [PhCOCH₂SeR] have been prepared. These compounds have been characterized by elemental analyses, IR and NMR (¹H, ¹³C, ⁷⁷Se) spectroscopy. The compounds, [PhC(OCH₂CH₂)CH₂Se]₂ and (PhCOCH₂Se)₂ have been structurally characterized by single crystal X-ray diffraction analyses. The former shows intra-molecular Se‐?‐?‐O interaction, while the latter exhibits inter-molecular nonbonding Se‐?‐?‐O interaction.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]     

Synthesis of new α-hydroxyphosphonates and α-acetoxyphosphonates

A series of new α-hydroxyphosphonate (5–14) have been synthesized in high yields by reaction of β-chloro-α,β-unsaturated aldehydes (1–4) and trialkyl phosphite in the presence of chlorotrimethylsilane at room temperature under solvent-free conditions. In addition, compounds (5–14) were reacted with acetic anhydride in DBU to give the new α-acetoxyphosphonate derivatives (15–23). All these phosphonates (5–23) were obtained as mixtures of two (E and Z) isomers and fully characterized by multinuclear (¹H, ¹³C, and ³¹P) NMR, IR spectroscopy and HRMS.     

Synthesis,Stability and Reactivity of α-Fluorinated Azidoalkanes

Organic α-fluorinated azidoalkanes appeared in the literature for the first time half a century ago. However, for a long time they remained undeveloped and were regarded as chemical curiosities. Recent advances in the preparation of α-fluorinated azidoalkanes as well as studies on their stability and reactivity opened up their broader synthetic potential for the preparation of valuable fluorinated and non-fluorinated compounds.     

Chiral nickel(II) complexes in the preparation of 11C- and 18F-labelled enantiomerically pure α-amino acids

Positron emission tomography (PET) utilises positron emitting radiopharmaceuticals in the study of metabolic and physiological processes. FDG-PET is a useful technique for tumour detection; however FDG has disadvantages. The incorporation of labelled amino acids into brain tumours and into some other organs with high physiological consumption of glucose is a superior diagnostic method due to its much higher selectivity compared to FDG. A Ni(II) complex with a Schiff base of BPB and glycine was one of the first glycine synthons used for asymmetric synthesis of carbon-11 and fluorine-18 labelled α-amino acids. A similar complex was employed for routine preparation of [(18)F]FET. Physico-chemical investigations allowed us to design modified complexes with much stronger stereodiscriminative power including stereospecific ones. Chiral nickel complexes are also used for the preparation of tailored amino acids for the incorporation into peptides followed by labelling the peptides with fluorine-18 labelled "click" reagents. This review covers PET applications of Ni(II) complexes of Schiff base of BPB and α-amino acids from 1989 to date.     

Synthesis and structural study of α-amino- and α,ω-diamino oligoamides-11

α-Amino (MAO) and α,ω-diamino (DAO) oligoamides were prepared using dodecylamine or 1,6 diaminohexane as a chain limitator. These were characterized by GPC, ¹H-NMR and ¹³C-NMR; molecular models: N-dodecyldodecanamide and 1,6 bis dodecylaminohexane; trifluoroacetylation was used to dissolve the oligoamides. DAO prepared in the melt contains two types of chains, depending on the position of the limitator. When oligomers were prepared in solution using the Yamazaki method, the presence of residual phosphorus derivatives in the oligoamides could not be avoided.     

Synthesis of new racemic α-heterocyclic α,α-diaminoesters and α-aminoester carboxylic

New racemic α-aminoester and α,α-diaminoesters derivatives were synthesized by nucleophilic substitution of methyl α-azido glycinate N-benzoylated with 3-amino-1,2,4-triazole, 2-tetrahydrofuran-2-ylmethan-amine and 2-methyl quinolin-4-amine.