Facile stereoselective syntheses of aryl substituted α,β‐unsaturated esters containing a trifluoromethyl group

The Suzuki‐type cross‐coupling reaction of arylboronic acids 3 with ethyl (Z)‐3‐iodo‐4,4,4‐trifluoro‐2‐butenoate 2 , which was generated by hydroiodination of available ethyl 4,4,4‐trifluoro‐2‐butynoate 1 , to afford ethyl (E)‐3‐aryl‐4,4,4‐trifluoro‐2‐butenoates 4 , was studied for the first time. It was found that under the optimum conditions the cross‐coupling reaction could readily give 4 as the sole E‐isomer in 76–91% yields. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:287–290, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10032     

Synthesis of optically active N‐protected α‐aminoketones and α‐amino alcohols

A series of optically active N‐protected α‐aminoketones were synthesized via the Grignard reaction of the Weinreb amides of the N‐tert‐butoxycarbonyl amino acids. Reduction of the α‐aminoketones by sodium borohydride resulted in the corresponding 1,2‐amino alcohols. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:603–606, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10195     

Unsaturated cyclic α‐hydroxyphosphonates

In an attempt to find novel plant growth regulators, a series of unsaturated cyclic α‐hydroxyphosphonates were synthesized by the addition reactions of 4‐aryl‐5,5‐dimethyl‐1,3,2‐dioxaphosphinane 2‐oxides with 5‐aryl‐2E,4E‐pentadienaldehydes. The cis and trans isomers of the products were isolated. The structures of all products were confirmed by elemental analyses and by NMR and IR spectroscopy or MS. The results of preliminary bioassay indicate that the title compounds possess potential inhibitory activity on the elongation of wheat coleoptile. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:266–268, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10039     

Synthesis of β‐monosubstituted α,β‐unsaturated amides with Z‐selectivity using diphenylphosphonoacetamides

The utility of diphenylphosphonoacetamides [(PhO)₂P(O)CH₂CONRR′] as Horner–Wadsworth–Emmons reagents was examined with five different patterns of substitution upon the amide nitrogen atom ( 2a : R, R′ = CH₂Ph; 2b : R = CH₂Ph, R′ = H; 2c : R = Me, R′ = OMe; 2d : R, R′ = Ph; 2e : R, R′ = (CH₂)₄). The reaction of 2a was found to be Z‐selective for aromatic aldehydes with selectivities up to 95:5. Reagent 2b led to reasonable selectivity for both benzaldehyde (85:15) and 3‐phenylpropionaldehyde (87:13), while 2c was somewhat effective for only the latter alkyl aldehyde (83:17). Compounds 2d and 2e exhibited slightly lower selectivities compared with 2a . © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:515–523, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20054     

Synthesis of α‐fluoro‐β‐trifluoromethyl alka‐2,4‐dienes

The palladium/copper(I) iodide cocatalyzed coupling reaction of (Z)‐α‐fluoro‐β‐trifluoromethylstannanes ( 1 ) with vinyl iodides ( 2 ) has been explored giving substituted α‐fluoro‐β‐trifluoromethyl dienes ( 3 ) in 33–95% yields. In studies we have conducted so far, a larger number of the configurations of the products remained unchanged (cases 3a, 3e–h ), though in several cases (cases 3b–d ) two configurations of the products were obtained. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:208–211, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20284     

Phosphoryl group differentiating α‐amino acids from β‐ and γ‐amino acids in prebiotic peptide formation

In recent years β‐amino acids have increased their importance enormously in defining secondary structures of β‐peptides. Interest in β‐amino acids raises the question: Why and how did nature choose α‐amino acids for the central role in life? In this article we present experimental results of MS and ³¹P NMR methods on the chemical behavior of N‐phosphorylated α‐alanine, β‐alanine, and γ‐amino butyric acid in different solvents. N‐Phosphoryl α‐alanine can self‐assemble to N‐phosphopeptides either in water or in organic solvents, while no assembly was observed for β‐ or γ‐amino acids. An intramolecular carboxylic–phosphoric mixed anhydride (IMCPA) is the key structure responsible for their chemical behaviors. Relative energies and solvent effects of three isomers of IMCPA derived from α‐alanine (2a–c), with five‐membered ring, and five isomers of IMCPA derived from β‐alanine (4a–e), with six‐membered ring, were calculated with density functional theory at the B3LYP/6‐31G** level. The lower relative energy (3.2 kcal/mol in water) of 2b and lower energy barrier for its formation (16.7 kcal/mol in water) are responsible for the peptide formation from N‐phosphoryl α‐alanine. Both experimental and theoretical studies indicate that the structural difference among α‐, β‐, and γ‐amino acids can be recognized by formation of IMCPA after N‐phosphorylation. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 232–241, 2003     

Reaction of Grignard Reagents with Diethyl Perfluoroacyl (1-Cyanoethyl)phosphonates. Synthesis of Perfluoroalkylated α,β-Unsaturated Nitriles with Predominant Z-Selectivity

ＩｎｔｒｏｄｕｃｔｉｏｎＲｅｃｅｎｔｌｙｍｕｃｈａｔｔｅｎｔｉｏｎｈａｓｂｅｅｎｄｅｖｏｔｅｄｔｏｔｈｅｓｙｎｔｈｅｓｉｓｏｆα ,β ｕｎｓａｔｕｒａｔｅｄｎｉｔｒｉｌｅｓｓｉｎｃｅｔｈｅｙａｒｅｉｍ ｐｏｒｔａｎｔｓｔｒｕｃｔｕｒａｌｆｅａｔｕｒｅｏｆｓｅｖｅｒａｌｎａｔｕｒａｌｌｙｏｃｃｕｒｒｉｎｇｂｉ ｏｌｏｇｉｃａｌｌｙａｃｔｉｖｅｃｏｍｐｏｕｎｄｓ .1,2 Ｔｈｅｉｎｔｒｏｄｕｃｔｉｏｎｏｆｆｌｕｏ ｒｉｎｅｏｒｔｒｉｆｌｕｏｒｏｍｅｔｈｙｌｇｒｏｕｐｉｎｔｏｂｉｏｌｏｇｉｃａｌｌｙａｃｔｉｖ…     

Stereoselective synthesis of 1,4,2‐oxazaphosphorines as precursors of chiral α‐aminophosphonic acids by intramolecular heterocyclization of β‐aldiminoalkylphosphites

The intramolecular version of nucleophilic additon of phosphites to imines was carried out for the first time taking as an example β‐aldiminoalkylphosphites, formed from chlorophosphites and β‐aldiminoalcohols [N‐(benzylidene)‐2‐aminoethanol and R‐(+)‐N‐(benzylidene)‐2‐aminobutanol‐1]. In these reactions, stereoisomeric 1,4,2‐oxazaphosphorines were obtained in good yields. R‐(+)‐N‐(benzylidene)‐2‐aminobutanol‐1 being used as a precursor, nucleophilic attack by P(III) atom on electrophilic C atom of the CN group proceeds stereospecifically with participation of only re‐face of the two possible diastereotopic faces of the imine double bond to give the epimeric at phosphorus (3R,5R)‐2‐(β‐chloroethyl)‐2‐oxo‐3‐phenyl‐5‐ethyl‐1,4,2‐oxazaphosphorines as precursors of nonracemic α‐aminophosphonic acids. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:56–61, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10054     

Synthesis of α‐aminophosphinates by the hydrophosphinylation of imines

Numerous substituted α‐aminophosphinates were synthesized by addition of alkyl and phenyl H‐phosphinates to aromatic imines and characterized. Modest diastereoselectivity was observed in the reaction. The size of the substituents exerts a small effect on the diastereoselectivity of P C bond formation. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:235–240, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10133     

Heterocyclic synthesis containing bridgehead nitrogen atom: Synthesis of 3‐[(2H)‐2‐oxobenzo[b]pyran‐3‐yl]‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazine and thiazole derivatives

The reaction of 2H‐2‐oxobenzo[b]pyran‐3‐hydrazide ( 2 ) with carbon disulfide in basic DMF afforded potassium thiocarbamate 3 , which readily underwent heterocyclization upon its reaction with hydrazine and/or phenacyl bromide to yield 1,2,4‐tiazole ( 4 ) and thiazole 7 derivatives, respectively. Condensation of 4 with substituted phenacyl bromide and/or chloranil gave 1,2,4‐triazole[3,4‐b]thiadiazine ( 5a,b ) and 3,10‐bis‐[2H‐2‐oxobenzo[b]pyran‐3‐yl]‐6,13‐dichloro‐bis‐1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazino[5′,6′‐b:5′,6′‐e]cyclohexa‐1,4‐diene ( 6 ), respectively. Cyclization of thiosemicarbazide 10 by refluxing it in sodium hydroxide and/or phosphoryl chloride afforded triazole 13 and thiadiazole 15 derivatives, respectively. Also, 10 reacted with phenacyl bromide in the presence of anhydrous sodium acetate to give the oxothiazolidine derivative 17 . The structure of the synthesized compounds were confirmed by elemental analyses, IR, ¹H NMR, and mass spectra. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:114–120, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10109     

Photodesulfurization of 2,4‐diaryl‐1,2, 4‐triazole‐3‐thiones

Irradiation of triazole thiones in thin‐film reactor furnished the corresponding desulfurized triazoles in good yield. The required triazole thiones were synthesized from the respective acid hydrazide and isothiocyanate. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:269–272, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10140     

3‐Aryl‐5‐furylpyrazolines and their biological activities

Aryl‐furyl substituted pyrazolines 2a–c and 4a–c were prepared by the reaction of α,β‐unsaturated carbonyl compounds with hydrazine or phenyl hydrazine. N‐chloroacetyl derivatives 3a–c were obtained by the N‐acetylation of 2a–c . The antibacterial activities of synthesized pyrazolines were examined by employing the disk‐diffusion technique. All synthesized compounds showed antibacterial effects in 1200 μg concentration. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:345–347, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10159     

Synthesis of 3′‐1,2,4‐triazolo‐ and 3′‐1,3,4‐thiadiazoliminothymidines

New 5′‐acetyl‐3′‐1,3,4‐thiadiazoliminothymidines 11, 14 were prepared, via spontaneous rearrangments, by cycloaddition of 5′‐acetyl‐3′‐deoxy‐3′‐isothiocyanatothymidine 9 with 1‐aza‐2‐azoniaallene hexachloantimonates. Similary, 3′‐cyano analogue 19 was reacted with the same cumulenes to furnish 3′‐1,2,4‐triazolo‐thymidines 22, 24 , and 26 . Deblocking of the acylated products afforded the free nucleosides. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:298–303, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10146     

Cycloaddition of bis‐1,3‐dipolar reagents to 1,3‐diarylprop‐2‐en‐1‐ones

Bis pyrazolines and isoxazolines were prepared by 1,3‐dipolar cycloaddition of benzene‐1,3/1,4‐dicarboxaldehyde dihydrazones and dioximes to 1,3‐diaryl‐prop‐2‐en‐1‐ones. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:379–383, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10169     

Convenient synthesis of optically active α‐hydroxyphosphinic acids

The reaction of O‐menthyl phenylphosphonite 1 with aromatic aldehydes in the presence of Me₃SiCl provided the O‐menthyl α‐hydroxyphosphinates 2 . Acidic hydrolysis of 2 gave the corresponding α‐hydroxyphosphinic acids 3 . The (+)‐enantiomer of 3a and 3b , adduct of benzaldehyde and 4‐methylbenzaldehyde respectively, were obtained via multiple recrystallization. The absolute configuration of (+)‐ 3a was determined as S by X‐ray crystallography. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:312–315, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10150     

Conversion of 2(3H)‐furanones into 1,3,4‐oxadiazoles

A series of 2‐phenyl‐5‐alkenyl‐1,3,4‐oxadiazoles were synthesized in high yields from the corresponding dicarbonylhydrazides through cyclodehydration. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:570–574, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10197     

3‐Methylthio‐pyrano[4,3‐c]pyrazol‐4(2H)‐ones from 3‐(bis‐methylthio)methylene‐2H‐pyran‐2,4‐diones and hydrazines

A useful synthesis of 3‐methylthio‐6‐methyl‐pyrano[4,3‐c]pyrazol‐4(2H)‐ones via 3‐(bis‐methylthio)methylene‐5,6‐dihydro‐6‐alkyl(aryl)‐2H‐pyran‐2,4‐dione with hydrazine as well as methyl and phenyl hydrazines is described and the mechanism of the formation is discussed. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:342–344, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10158     

Efficient synthesis and dehydration reaction of trichloromethylated 2‐(3‐phenyl‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐4‐aryl‐5‐alkylthiazoles

A convenient method for the synthesis of a novel series of 11, specifically substituted, noncondensed 5,5‐bicycles 2‐[3‐phenyl‐5‐hydroxy‐5‐trichloromethyl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl]‐4‐aryl‐5‐alkylthiazoles ( 3a–k ; 65–94% yield) from the reactions of 3‐phenyl‐5‐hydroxy‐5‐trichloromethyl‐4,5‐dihydro‐1H‐1‐pyrazolethiocarboxyamide ( 1 ) with substituted 2‐bromo‐4′‐acetophenones ( 2a–f ) and 2‐bromo‐4′‐propiophenones ( 2g–k ) is reported. Dehydration of compounds 3a–k with a mixture of concentrated sulfuric acid/chloroform furnished the corresponding 2‐[3‐phenyl‐5‐trichloromethyl‐1H‐pyrazol‐1‐yl]‐4‐aryl‐5‐alkylthiazoles ( 4a–k ) in good yields (61–93%). © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:132–137, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10113     

Diastereospecific synthesis of (S,S)‐2‐substituted‐4,4‐diphenyl‐3, 1‐oxazabicyclo[3.3.0]octanes

(S,S)‐2‐Substituted‐4,4‐diphenyl‐3,1‐oxazabicyclo[3.3.0]octanes were synthesized diaster‐eospecifically from aldehydes and (S)‐2‐(hydroxydiphenylmethyl)pyrrolidine, which was obtained from L ‐proline, under acid‐catalyzed conditions in anhydrous toluene. The stereospecificity of the condensation reaction is discussed. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:42–45, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10064     

Synthesis and antimicrobial activity of N‐substituted N′‐[6‐methyl‐2‐oxido‐1,3,2‐dioxaphosphinino(5,4‐b)pyridine‐2‐yl]ureas

N‐Substituted N′‐[6‐methyl‐2‐oxido‐1,3,2‐dioxaphosphinino(5,4,‐b)pyridine‐2‐yl]ureas have been accomplished by condensation of equimolar quantities of chlorides of various carbamidophosphoric acids ( 3 ) with 3‐hydroxyl‐6‐methyl‐2‐pyridinemethanol (lutidine diol) ( 4 ) in the presence of triethylamine in dry toluene–tetrahydrofuran (1:1) mixture at 45–50°C. Their structures were established by elemental analyses, IR, ¹H NMR, ¹³C NMR, and ³¹P NMR spectral data. Their antifungal and antibacterial activity is also evaluated. Most of these compounds exhibited moderate antimicrobial activity in the assays. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:509–512, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10181