A facile stereoselective synthesis of (E)‐α‐silylvinyl sulfides via hydromagnesiation of alkynylsilanes

Hydromagnesiation of alkynylsilanes 1 in diethyl ether gave (Z)‐α‐silylvinyl Grignard reagents 2 , which reacted with arylsulfenyl chlorides 3 to afford stereoselectively (E)‐α‐silylvinyl sulfides 4 in good yields. (E)‐α‐Silylvinyl sulfides 4 could undergo the cross‐coupling reactions with Grignard reagents in the presence of NiCl₂(PPh₃)₂ to give stereoselectively (Z)‐1,2‐disubstituted vinylsilanes 5 . © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:644–647, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20165     

Diastereoselective addition of hypophosphorous acid to N‐(R)‐α‐methylbenzyl‐substituted schiff bases

The addition of hypophosphorous acid to an azomethine bond of N‐(R)‐α‐methylbenzyl Schiff bases of a variety of aldehydes led to the formation of N‐(R)‐α‐methylbenzylamino‐(S)‐methanephosphonous acids in 100% diastereoselectivity. This fact allows us to suggest the probable mechanism of the Strecker‐like reaction between hypophosphorous acid, an aldehyde, and (R)‐α‐methylbenzylamine. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:35–37, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20406     

A novel stereoselective synthesis of (Z)‐α‐arylsulfanyl‐α,β‐unsaturated ketones via Stille coupling of (E)‐α‐arylsulfanylvinylstannanes with acyl halides

(E)‐α‐Arylsulfanylvinylstannanes react with acyl halides in the presence of a catalytic amount of Pd(PPh₃)₄ and CuI cocatalyst to give stereoselectively the corresponding (Z)‐α‐arylsulfanyl‐α,β‐unsaturated ketones in good yields. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:218–223, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20536     

(E)‐,(Z)‐Parallel Preparative Methods for Stereodefined β,β‐Diaryl‐ and α,β‐Diaryl‐α,β‐unsaturated Esters: Application to the Stereocomplementary Concise Synthesis of Zimelidine

Parallel and practical methods for the preparation of both (E)‐ and (Z)‐β‐aryl¹‐β‐aryl²‐α,β‐unsaturated esters 1 and (E)‐ and (Z)‐α‐aryl¹‐β‐aryl²‐α,β‐unsaturated esters 2 are described. These methods involve accessible, robust, stereocomplementary N‐methylimidazole (NMI)‐mediated enol tosylations (14 examples, 70–99 % yield), as well as stereoretentive Suzuki–Miyaura cross‐couplings (36 examples, 64–99 % yield). The highlighted feature of the present protocol is the use of parallel and stereocomplementary approaches to obtain highly (E)‐ and (Z)‐pure products 1 and 2 by utilizing sequential enol tosylations and cross‐coupling reactions. An expeditious and parallel synthesis of (E)‐ and (Z)‐zimelidine ( 3 ), which is a highly representative selective serotonin reuptake inhibitor (SSRI), was performed by utilizing the present methods.     

Stereospecific synthesis of a family of novel (E)‐2‐aryl‐1‐silylalka‐1,4‐dienes or (E)‐4‐aryl‐5‐silylpenta‐1,2,4‐trienes via a cross‐coupling of (Z)‐silyl(stannyl)ethenes with allyl halides or propargyl bromide

Stereospecific synthesis of a family of novel (E)‐2‐aryl‐1‐silylalka‐1,4‐dienes or (E)‐4‐aryl‐5‐silylpenta‐1,2,4‐trienes via a cross‐coupling of (Z)‐silyl(stannyl)ethenes with allyl halides or propargyl bromide is described. In the reaction with allyl bromide, either a Pd(dba)₂? CuI combination (dba, dibenzylideneacetone) in DMF or copper(I) iodide in DMSO–THF readily catalyzes or mediates the coupling reaction of (Z)‐silyl(stannyl)ethenes at room temperature, producing novel vinylsilanes bearing an allyl group β to silicon with cis ‐disposition in good yields. Allyl chlorides as halides can be used in the CuI‐mediated reaction. CuI alone much more effectively mediates the cross‐coupling reaction with propargyl bromide in DMSO–THF at room temperature compared with a Pd(dba)₂? CuI combination catalysis in DMF, providing novel stereodefined vinylsilanes bearing an allenyl group β to silicon with cis ‐disposition in good yields. Copyright © 2008 John Wiley & Sons, Ltd.     

A highly efficient synthesis of (Z)‐1‐aryl‐2‐silyl‐1‐ stannylethenes and their conversion to (E)‐2‐ arylethenyl‐, (Z)‐2‐(2‐pyridyl)ethenyl‐ and allenyl‐silanes

A Pd(dba)₂–P(OEt)₃ combination allowed the silastannation of arylacetylenes, 1‐hexyne or propargyl alcohols with tributyl(trimethylsilyl)stannane to take place at room temperature, producing (Z)‐2‐silyl‐1‐stannyl‐1‐substituted ethenes in high yields. Novel silyl(stannyl)ethenes were fully characterized by ¹H‐, ¹³C‐, ²⁹Si‐ and ¹¹⁹Sn‐NMR as well as infrared and mass analyses. Treatment of a series of (Z)‐1‐aryl‐2‐silyl‐1‐stannylethenes and (Z)‐1‐(3‐pyridyl)‐2‐silyl‐1‐stannylethene with hydrochloric acid or hydroiodic acid in the presence of tetraethylammonium chloride (TEACl) or tetrabutylammonium iodide (TBAI) led to the exclusive formation of (E)‐trimethyl(2‐arylethenyl)silanes with high stereoselectivity. A similar reaction of (Z)‐1‐(2‐anisyl)‐2‐silyl‐1‐stannylethene also produced E‐type trimethyl[2‐(2‐anisyl)ethenyl]silane, while (Z)‐trimethyl [2‐(2‐pyridyl)ethenyl]silane was produced exclusively from (Z)‐1‐(2‐pyridyl)‐2‐silyl‐1‐stannylethene. Protodestannylation of (Z)‐1‐[hydroxy(phenyl)methyl]‐2‐silyl‐1‐stannylethene with trifluoroacetic acid took place via the β‐elimination of hydroxystannane, providing trimethyl(3‐phenylpropa‐1,2‐dienyl)silane quite easily. The destannylation products were also fully characterized. Copyright © 2007 John Wiley & Sons, Ltd.     

Polymerization of higher linear α‐olefins with (CH3)2Si(2‐methylbenz[e]indenyl)2ZrCl2

Poly‐α‐olefins ranging from poly‐1‐pentene to poly‐1‐octadecene with narrow polydispersities were synthesized with (CH₃)₂Si(2‐methylbenz[e]indenyl)₂ZrCl₂ and methylaluminoxane at polymerization temperatures (T_p 's) ranging from −15 to 180 °C and were characterized by gel permeation chromatography, NMR spectroscopy, and differential scanning calorimetry. The molar masses of the homopolymers obtained with (CH₃)₂Si(2‐methylbenz[e]indenyl)₂ZrCl₂ were notably higher than those of poly‐α‐olefins synthesized with other zirconium‐based metallocenes under similar conditions. The temperature dependence of the molar mass distribution of the poly‐α‐olefins can be described by a common exponential decay function regardless of the investigated monomer. At T_p 's ranging from 20 to 100 °C, moderate isotacticity prevailed, but outside this temperature range, the polymers were less stereoregular. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2333–2339, 2000     

Stereoselective synthesis of trisubstituted alkenes containing (Z)‐allylthio units from the acetates of Baylis–Hillman adducts

A series of trisubstituted alkenes containing (Z)‐allylthio moieties as key structural units, that is, sodium (Z)‐allyl thiosulfates, symmetrical di(Z‐allyl) sulfides, and di(Z‐allyl) disulfides, unsymmetrical diallyl sulfides were prepared in moderate to good yields via chemical transformations from the acetates of Baylis‐‐Hillman adducts. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:188–198, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20394     

A facile stereoselective synthesis of (E)‐1,2‐disubstituted vinylic selenides via hydromagnesiation of alkylarylacetylenes

Hydromagnesiation of alkylarylacetylenes 1 in diethyl ether gave (E)‐α‐arylvinyl Grignard reagents 2 , which reacted with arylselenenyl bromides 3 in THF to afford stereoselectively (E)‐1,2‐disubstituted vinylic selenides 4 in good yields. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:65–68, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20066     

Photoinduced and thermal reactions of α‐cyano‐β‐bromomethylcinnamide with 1‐benzyl‐1,4‐dihydronicotinamide

The photoinduced reaction of a mixture of (Z)‐α‐cyano‐β‐bromomethylcinnamide (1) and (E)‐α‐cyano‐β‐bromomethylcinnamide (2) with 1‐benzyl‐1, 4‐dihydronicotinamide produces a mixture of the (E)‐ and (Z)‐ isomers of α‐cyano‐β‐methylcinnamide (3 and 4). Using spin‐trapping technique for monitoring reactive intermediate, it is shown that the reaction proceeds via electron transfer‐debromination‐H abstraction mechanism. The thermal reaction of the same substrate with BNAH at 60°C in the dark gives three products: the (E)‐ and (Z)‐isomers of α‐cyano‐β‐methylcinnamide and a dehydrodimeric product; 2, 7‐dicyano‐3, 6‐diphenylocta‐2, 4, 6‐trien‐1, 8‐dioic amide (7). Based on product analysis, scavenger experiment and cyclic voltammetry, an electron transfer‐debromination‐disproportionation mechanism is proposed.     

“One‐pot” synthesis of (Z)‐2‐aryl‐1‐(2‐cyanoethyl)ethenylphosphonates via hexamethylphosphoramide‐promoted sequential transformation

(Z)‐2‐Aryl‐1‐(2‐cyanoethyl)ethenylphosphonates were synthesized by the hexamethylphosphoramide‐promoted sequential transformation of tetra‐alkyl methanediphosphonates, by the action of potassium tert‐butoxide, and then by acrylonitrile and aldehydes. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:116–119, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10004     

An activated catalyst RhH(PPh3)4‐dppe‐ Me2S2 for α‐methylthiolaton of α‐phenyl ketones

In the presence of catalytic amounts of RhH(PPh₃)₄, 1,2‐bis(diphenylphosphino)ethane (dppe), and dimethyl disulfide, cyclic and acyclic α‐phenyl ketones reacted with p‐cyano‐α‐methylthioa‐ cetophenone giving α‐methylthio‐α‐phenylketones. The activated catalyst containing dimethyl disulfide was effective for the α‐methylthiolation reaction of these less reactive substrates. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 22:18–23, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20650     

Synthesis of (4Z)‐4‐(Arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones by the Reaction of Ethyl (2Z)‐3‐Aryl‐2‐isothiocyanatoprop‐2‐enoates with Organolithium Compounds

A convenient one‐pot method for the preparation of (4Z)‐4‐(arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones 2 and 3 from ethyl (2Z)‐3‐aryl‐2‐isothiocyanatoprop‐2‐enoates 1 , which can be easily prepared from ethyl 2‐azidoacetate and aromatic aldehydes, has been developed. Thus, these α‐isothiocyanato α,β‐unsaturated esters were treated with organolithium compounds, including lithium enolates of acetates, to provide 5‐substituted (4Z)‐4‐(arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones, 2 , and 2‐[(4Z)‐(4‐arylmethylidene)‐5‐ethoxy‐2‐thioxo‐1,3‐oxazolidin‐5‐yl]acetates, 3 .     

(E/Z)‐Isomerization of (all‐E)‐5,6‐Diepikarpoxanthin

(all‐E)‐5,6‐Diepikarpoxanthin (=(all‐E,3S,5S,6S,3′R)‐5,6‐dihydro‐β,β‐carotene‐3,5,6,3′‐tetrol; 1 ) was submitted to thermal isomerization and I₂‐catalyzed photoisomerization. The structures of the main products, i.e. (9Z)‐ ( 2 ), (9′Z)‐ ( 3 ), (13Z)‐ ( 4 ), (13′Z)‐ ( 5 ), and (15Z)‐5,6‐diepikarpoxanthin ( 6 ), were determined by their UV/VIS, CD, ¹H‐NMR, and mass spectra. In addition, (9Z,13′Z)‐ or (13Z,9′Z)‐ ( 7 ), (9Z,9′Z)‐ ( 8 ), and (9Z,13Z)‐ or (9′Z,13′Z)‐5,6‐diepikarpoxanthin ( 9 ) were tentatively identified as minor products of the I₂‐catalyzed photoisomerization.     

Efficient synthesis of 2‐substituted thieno[2,3‐d]pyrimidin‐4(3H)‐ones via an iminophosphorane

The carbodiimides 4 , obtained from reactions of iminophosphorane 3 with aromatic isocyanates, were reacted with secondary amines to give 2‐dialkylamino‐5‐ethyl‐6‐methyl‐thieno[2,3‐d]pyrimidin‐4(3H)‐ones 6 in the presence of catalytic amount of EtONa. Reactions of 4 with phenols or ROH in the presence of the catalytic amount of K2CO₃ or RONa gave 2‐aryloxy‐ or 2‐alkoxy‐5‐ethyl‐6‐methyl‐thieno[2,3‐d]pyrimidin‐4(3H)‐ones 6 in satisfactory yields. The effects of the nucleophiles on cyclization have been investigated. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:266–270, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20424     

Annulenoide Tetrathiafulvalene:, 5,16‐Bis(1,3‐benzodithiol‐2‐yliden)‐5,16‐dihydrotetraepoxy‐ und 5,16‐Bis(1,3‐benzodithiol‐2‐yliden)‐5,16‐dihydrotetraepithio[22]annulene(2.1.2.1)

Annulenoid Tetrathiafulvalenes: 5,16‐Bis(1,3‐benzodithiol‐2‐ylidene)‐5,16‐dihydrotetraepoxy‐ and 5,16‐Bis(1,3‐benzodithiol‐2‐ylidene)‐5,16‐dihydrotetraepithio[22]annulenes(2.1.2.1) The title compounds are among the first tetrathiafulvalenes with annulene spacers, here with tetraepoxy‐[22]annulene(2.1.2.1) (see 3a ), tetraepithio[22]annulene(2.1.2.1) (see 3b ), and diepithiodiepoxy[22]annulene(2.1.2.1) (see 23 ) units. The annulenoid tetrathiafulvalenes 3a and 3b are prepared by cyclizing McMurry coupling of the 5,5′‐(1,3‐benzodithiol‐2‐ylidenemethylene)bis[furan‐ or thiophene‐2‐carbaldehydes] ( 8a or 8b , resp.) or by Wittig reaction of (1,3‐benzodithiol‐2‐yl)tributylphosphonium tetrafluoroborate ( 13b ) with tetraepoxy[22]annulene(2.1.2.1)‐1,12‐dione 20 (formation of 3a ) or diepithiodiepoxy[22]annulene(2.1.2.1)‐1,12‐dione 22 (formation of 23 ). The annulenoide tetrathiafulvalene 3a is obtained as a mixture of the isomers (E,E)‐ and (Z,Z)‐ 3a . At 130°, (Z,Z)‐ 3a rearranges quantitatively into the (E,E)‐isomer. Isomer (E,E)‐ 3a is a dynamic molecule, where the (E)‐ethene‐1,2‐diyl bridges rotate around the adjacent σ‐bonds. The tetraepithioannulene derivative 3b as well as 23 only exist in the (Z,Z)‐configuration. The oxidation of (E,E/Z,Z)‐ 3a with Br₂ yields the annulene‐bridged tetrathiafulvalene dication (E,E)‐ 3a _Ox, while with 4,5‐dichloro‐3,6‐dioxocyclohexa‐1,4‐diene‐1,2‐dicarbonitrile (DDQ) obviously only the radical cation 3a _Sem is formed, which belongs to the class of cyanine‐like violenes. The annulenoide tetrathiafulvalenes 3b and 23 , which exist only in the (Z,Z)‐configuration, obviously for steric reasons, cannot be oxidized by DDQ. Electrochemical studies are in agreement with these results.     

Hydrogen‐bonding patterns in enaminones: (2Z)‐1‐(4‐bromophenyl)‐2‐(pyrrolidin‐2‐ylidene)ethanone and its piperidin‐2‐ylidene and azepan‐2‐ylidene analogues

The title compounds, namely (2Z)‐1‐(4‐bromophenyl)‐2‐(pyrrolidin‐2‐ylidene)ethanone, C₁₂H₁₂BrNO, (I), (2Z)‐1‐(4‐bromophenyl)‐2‐(piperidin‐2‐ylidene)ethanone, C₁₃H₁₄BrNO, (II), and (2Z)‐2‐(azepan‐2‐ylidene)‐1‐(4‐bromophenyl)ethanone, C₁₄H₁₆BrNO, (III), are characterized by bifurcated intra‐ and intermolecular hydrogen bonding between the secondary amine and carbonyl groups. The former establishes a six‐membered hydrogen‐bonded ring, while the latter leads to the formation of centrosymmetric dimers. Weak C—H...Br interactions link the individual molecules into chains that run along the [011], [101] and [101] directions in (I)–(III), respectively. Additional weak Br...O, C—H...π and C—H...O interactions further stabilize the crystal structures.     

Copper Salt‐Controlled Divergent Reactivity of [Cu]CF2PO(OEt)2 with α‐Diazocarbonyl Derivatives

Herein, we report a copper salt‐controlled divergent reactivity toward α‐diazocarbonyl compounds. By a simple change of the copper counteranion under identical reaction conditions, the reported method allowed an easy access to either (Z)‐α‐fluorovinylphosphonate or alkyl‐SCF₂PO(OEt)₂ derivatives in good yields. Mechanistic studies were performed and suggested two different pathways to explain the formation of these products.     

Synthesis and antiproliferative activity of (Z + E)‐1‐[4‐(2‐(cyclopentadienyltricarbonylmanganese)‐2‐oxo‐ethoxy)phenyl]‐1,2‐di(p‐hydroxyphenyl)‐but‐1‐ene against breast cancer cells

This paper describes the synthesis of (Z + E)‐1‐[4‐(2‐(cyclopentadienyltricarbonylmanganese)‐2‐oxo‐ethoxy)phenyl]‐1,2‐di(p‐hydroxyphenyl)‐but‐1‐ene. Two synthetic pathways were explored. The best pathway consisted of the alkylation of 1,2‐bis‐[4‐(tert‐butyl‐dimethylsilyloxy)phenyl]‐1‐(4‐hydroxyphenyl)but‐1‐ene with BrCH₂COOEt. The ester obtained was transformed into the Weinreb amide by reaction with HN(OMe)Me–HCl. The reaction of lithium manganese tricarbonylcyclopentadienide with the Weinreb amide produced 1‐[4‐(2‐(cyclopentadienyltricarbonylmanganese)‐2‐oxo‐ethoxy)phenyl]‐1,2‐di(p‐tert‐butyldimethylsiloxyphenyl)‐but‐1‐ene. The deprotection of phenolic functions of the latter compound led to the formation of the final compound. The Z and E isomers could be separated but the isomerization of these isomers from one to another is an easy process. The Z + E compound 2 was tested against the hormone‐dependent MCF‐7 and hormone‐independent MDA‐MB‐231 breast cancer cell lines. The IC₅₀ values of compound 2 were 4.80 ± 2.00 µm and 4.79 ± 0.70 µm for MCF‐7 cells and MDA‐MB‐231 cells, respectively, which was three times better than the ferrocenyl analogue. Copyright © 2012 John Wiley & Sons, Ltd.     

A convenient synthesis of 2‐(1H‐1,2,4‐triazol‐1‐yl)‐2H‐1,4‐benzothiazine derivatives

A series of 2‐(1H‐1,2,4‐triazol‐1‐yl)‐2H‐1,4‐benzothiazines were designed and synthesized by condensation of 1,2,4‐triazole‐substituted ω‐bromoacetophenones and o‐aminothiophenols with the aid of K₂CO₃ under mild conditions with moderate to high yields. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:332–336, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20434