Reactivity of 2-halo-2H-azirines. Part 3: Dehalogenation of 2-halo-2H-azirine-2-carboxylates

The dehalogenation of 2-halo-3-phenyl-2H-azirine-2-carboxylates is described. Using sodium borohydride and tributyltin hydride 3-phenyl-2H-azirine-2-carboxylates were obtained in moderate yields. The synthesis of a new 2-bromo-2H-azirines with a chiral auxiliary, 10-phenylsulfonylisobornyl 2-bromo-3-phenyl-2H-azirine-2-carboxylate, is reported. Its dehalogenation led to 10-phenylsulfonylisobornyl 2H-azirine-2-carboxylate as single stereoisomer together with the formation of 10-phenylsulfonylisobornyl acetate.     

Assymetric synthesis of (2S,3R)- and (2S,3S)-[2-C;3-H] glutamic acid

We have developed a synthetic route for (2S,3R)- and (2S,3S)-[2-¹³C;3-²H] glutamic acids with high enantioselectivity. The key reactions in this synthesis are the asymmetric reduction of the 2,3-didehydroornithine derivative using the (S,S)-Et-DuPHOS-Rh catalyst and the oxidation of the δ-position by ruthenium catalysis.     

Amino-zinc-ene-enolate cyclisation: a short access to (2S,3R)- and (2S,3S)-3-benzylprolines (3-benzylpyrrolidine-2-carboxylic acids)

The synthesis of 3-benzylprolines can be easily achieved in a diastereoselective and enantioselective way via amino-zinc-ene-enolate cyclisation. Transmetalation of the cyclic zinc intermediate with Pd₂(dba)₃/P(o-Tolyl)₃ allowed functionalisation with an aromatic ring. One-pot hydrogenolysis and Boc-protection led to the cis-isomer readily usable for peptide synthesis. The trans-isomer was obtained by epimerisation of the α-centre in a sealed tube at 200 °C.     

Stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucines

A stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucine is disclosed. The key step of the reaction sequence involves, stereo- and regioselective bromohydration of 7, using a brominating agent derived in situ from N-bromosuccinimide and 2,6-lutidine, via intramolecular sulfinyl group participation.     

An efficient synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenyl piperidine and N-Boc-safingol

An efficient strategy has been developed for the stereo selective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenyl piperidine and N-Boc-safingol from benzaldehyde and N-Boc-imine.     

An efficient stereoselective synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine

A concise enantioselective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenylpiperidine 1 is described starting from l-phenyl-glycine and using a Grignard reaction as a key step.     

One pot synthesis using supported reagents system KSCN/SiO2-RNH3OAc/Al2O3: synthesis of 2-aminothiazoles and N-allylthioureas

A simple and efficient method has been developed for the synthesis of 2-aminothiazoles and N-allylthioureas from commercially available materials in one pot by using a supported reagents system, KSCN/SiO₂-RNH₃OAc/Al₂O₃, in which α-halo ketone reacts first KSCN/SiO₂ and the product, α-thiocyanatoketone, reacts with RNH₃OAc/Al₂O₃ to give the final product, 2-aminothiazoles, in good yield and allyl bromide reacts with KSCN/SiO₂ and the product, allyl isothiocyanate, reacts with RNH₃OAc/Al₂O₃ to give N-allylthiourea.     

Facile stereoselective synthesis of cis- and trans-3-alkoxyazetidin-2-ones

A highly stereoselective synthesis of cis- and trans-3-alkoxy-3-phenyl/benzylthioazetidin-2-ones is described. The reaction of α-chlorosulfide-β-lactams with various alcohols catalyzed by a Lewis acid such as ZnCl₂ in the presence of molecular sieves (3-4 Å) leads to cis-3-alkoxy-3-phenyl/benzylthio-β-lactams whereas treatment of potassium 2-alkoxy-2-phenylthioethanoate with appropriate Schiff's base using POCl₃ in the presence of triethylamine leads to the formation of trans-3-alkoxy-3-phenylthioazetidin-2-ones as major products.     

A convenient and new approach to the synthesis of ω-heterocyclic amino acids from carboxy lactams through ring-chain-transformation. Part 2: Synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid

Making use of amide activation, a convenient and short path synthesis of optically pure ω-heterocyclic-β-amino acids has been achieved from (1R,3R)- and (1R,3S)-5-oxo-1-(1-phenyl-ethyl)-pyrrolidine-3-carboxylic acid methyl ester. The key step of the synthesis involves a regiospecific ring-chain-transformation of the enaminones when subjected to 1,2-binucleophilic attacks. The method is illustrated by the synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid.     

The cis-2-alkyl-3-oxy-tetrahydropyran unit as a building block for new ionophores with C2-symmetry

The use of cis-2-alkyl-3-oxy-tetrahydropyran unit is reported as a novel structure for the design and synthesis of a new type of ionophore with C₂-symmetry. The synthesis of five macrolides and their complexation properties were investigated. The template effect as an effective tool to improve the selectivity and yield in the macrolactonization process is described.     

rac-BINAP-PdCl2 catalyzed Heck reactions of 3-formylquinolin-2-yl chlorides with methyl acrylate: synthesis of methyl 3-(3-formylquinolin-2-yl) acrylates

rac-BINAP-PdCl₂ catalytic system catalyzed Heck reaction of 3-formylquinolin-2-yl chlorides with methyl acrylate in DMA is described to the synthesis of methyl 3-(3-formyl-quinolin-2-yl)-acrylates, in good to excellent yields. The reaction could be also extended with other activated alkenes to afford Heck products. Fused-benzene ring in heterocyclic and carbocyclic moieties was found to enhance the yields.     

Solid-phase synthesis of 3-alkyl-8-arylamino-1H-imidazo[4,5-g]quinazolin-2(3H)-thiones and 3-alkyl-8-arylamino-1H-imidazo[4,5-g]quinazolin-2(3H)-ones

An efficient approach for the synthesis of 3-alkyl-8-arylamino-1H-imidazo[4,5-g]quinazolin-2(3H)-thiones and 3-alkyl-8-arylamino-1H-imidazo[4,5-g]quinazolin-2(3H)-ones on solid phase has been developed. The reaction conditions were readily amenable and the products were obtained in good yields and purities after their cleavage from the resin.     

Pd2dba3/P(i-BuNCH2CH2)3N: a highly efficient catalyst for the one-pot synthesis of trans-4-N,N-diarylaminostilbenes and N,N-diarylaminostyrenes

A Pd₂dba₃/P(i-BuNCH₂CH₂)₃N catalyzed one-pot synthesis of unsymmetrically substituted trans-4-N,N-diarylaminostilbenes and both symmetrically and unsymmetrically substituted N,N-diarylaminostyrene derivatives is reported. The procedure involves two or more palladium catalyzed sequential coupling reactions (an amination and an inter-molecular Heck reaction) in one-pot using the same catalyst system with two different aryl halides, including aryl chlorides and hetero aryl halides as the coupling partners.     

Synthesis of (2S,3R)- and (2S,3S)-[3-H1]-proline via highly stereoselective hydrolysis of a silyl enol ether

A straightforward synthesis of (2S)-[3,3-²H₂]-proline 1c and (2S,3R)- and (2S,3S)-[3-²H₁]-proline, 1b and 1a, respectively, has been devised. The key step of the route to the latter compounds involves highly stereoselective hydrolysis of the silyl enol ethers 3 and 3a, respectively, with protonation (deuteriation) from the re-face of the silyl enol ether.     

High-pressure structure of Li2CO3

The high-pressure behavior of Li₂CO₃ is studied up to 25 GPa with synchrotron angle-dispersive powder X-ray diffraction in diamond anvil cells and synthesis using a multi-anvil apparatus. A new non-quenchable hexagonal polymorph (P6₃/mcm, Z=2) occurs above 10 GPa with carbonate groups in a staggered configuration along the c-axis—a=4.4568(2) Å and c=5.1254(6) Å at 10 GPa. Two columns of face-shared distorted octahedra around the Li atoms are linked through octahedral edges. The oxygen atoms are coordinated to one carbon atom and four lithium atoms to form a distorted square pyramid. Splittings of X-ray reflections for the new polymorph observed above about 22 GPa under non-hydrostatic conditions arise from orthorhombic or monoclinic distortions of the hexagonal lattice. The results of this study are discussed in relation to the structural features found in other Me₂CO₃ carbonates (Me: Na, K, Rb, Cs) at atmospheric conditions.     

An efficient synthesis of optically active (2R,3R)-2-methyl-3-[(1R)-1-methylprop-2-enyl]cyclopentanone, a useful chiral building block for synthesis of vitamin D and steroids

An efficient synthesis of optically active (2R,3R)-2-methyl-3-[(1R)-1-methylprop-2-enyl]cyclopentanone, a useful chiral building block for synthesis of vitamin D and steroids, has been developed starting from readily accessible optically active secondary propargyl phosphate (R)-2, where the asymmetric Michael addition of a chiral allenyltitanium to alkylidenemalonate 3 is a key reaction.     

N-Functionalised polyfluoropyridazin-3(2H)-one derivatives

Pyridazin-3(2H)-one systems have very useful biological properties and have found many applications within the pharmaceutical and agrochemical industries but, in general, synthesis of polysubstituted analogues can be very difficult to achieve. An approach to the syntheses of polyfunctional pyridazinone systems involving sequential nucleophilic substitution reactions of N-aryl and N-THP protected 4,5,6-trifluoropyridazin-3(2H)-ones as the core scaffolds is described.     

Characterization and evaluation of Fe2O3/Al2O3 oxygen carrier prepared by sol–gel combustion synthesis

The sol-gel combustion synthesis (SGCS) for oxygen carrier (OC) to be used in chemical looping combustion (CLC) was first designed and experimented in this work, which is a new method of OC synthesis by combining sol-gel technique and solution combustion synthesis. Cheap hydrated metal nitrates and urea were adopted as precursors to prepare Fe₂O₃/Al₂O₃ OC at the molar ratio to unity (Fe1Al1), which was characterized through various means, including Fourier transforms infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), differential thermal analysis (DTA), X-ray diffractor (XRD), and N₂ isothermal adsorption/desorption method. FTIR analysis on the chemical structure of the dried gel of Fe1Al1 indicated that urea was partly hydrolyzed and the hydrated basic carbonate was formed by the combination of groups such as (Fe(_1−yAl_y)_1−xO_1−3x, CO₃²⁻ and -OH-. By analyzing the staged products during SGCS, calcination was found as a necessary step to produce Fe₂O₃/Al₂O₃ OC with separate phases of α-Fe₂O₃ and α-Al₂O₃. Through TGA-DTA, the decomposition of the dried gel was found to undergo five stages. The analysis of the evolved gases from the gel decomposition using FTIR partially confirmed the staged decomposition and assisted a better understanding of the mechanism of SGCS. XRD identification further substantiated the necessity of calcination to synthesize Fe₂O₃/Al₂O₃ OC with separate phases of α-Fe₂O₃ and α-Al₂O₃, though it was not necessary for the synthesis of single phase α-Fe₂O₃ and α-Al₂O₃. Structural characterization performed on N₂ adsorption analyzer displayed that the pore shape of Fe1Al1 particles was heterogeneous. Finally, H₂ temperature-programmed reduction (TPR) of Fe1Al1 products in TGA indicated that the reduction reaction of Fe1Al1 OC after calcination was a single step reaction from α-Fe₂O₃ to Fe, and calcination benefited to improve the transfer rate of the lattice oxygen from the OC to fuel H₂. Furthermore, four times of reduction and oxidization (redox) reaction by alternating with H₂ and air demonstrated the synthesized OC had good reactivity and sintering-resistance, much suitable to be used in the realistic CLC. Overall, the SGCS method was found superior to other existent methods to prepare Fe₂O₃/Al₂O₃ OC for CLC application.     

Stereoselective synthesis of 3-alkylidene/alkylazetidin-2-ones from azetidin-2,3-diones

Azetidin-2,3-diones have been used as synthons for the synthesis of C-3 alkylidene/alkylazetidin-2-ones. Some of the 3-alkylazetidin-2-ones are well known for their cholesterol absorption inhibitor activity. A regio and stereoselective Grignard reaction on a keto group followed by dehydration using PPh₃/CCl₄ reagent is a key step in this synthesis. Hydrogenation of the 3-alkylideneazetidin-2-ones provided stereoselectively cis-3-alkylazetidin-2-ones in very good yields.     

A convenient formal synthesis of (2S,3S)-3-hydroxy pipecolic acid

A convenient synthesis of (2S,3S)-3-hydroxy pipecolic acid starting from inexpensive and easily available l-(+)-tartaric acid has been described.