The Eschenmoser coupling reaction under continuous-flow conditions

• Sukhdeep Singh,
• J. Michael Köhler,
• Andreas Schober and
• G. Alexander Groß

Beilstein J. Org. Chem. 2011, 7, 1164–1172, doi:10.3762/bjoc.7.135

• desired Eschenmoser coupling products were obtained within 70 s residence time. The reaction kinetics was investigated and 15 examples of different building block combinations are given. Keywords: activation energy; episulfide; flow chemistry; keto imine; kinetics; S-alkylation; sulfide contraction

• ; triisopropyl phosphite; Introduction The Eschenmoser coupling [1][2] is a reaction method that yields β-enaminocarbonyl derivatives of type 4 by the elimination of sulfur (sulfide contraction) from an episulfide intermediate (Scheme 1). The reaction was described for the first time by Knott in 1955 [3] and

• - [5], sedamine alkaloid- [6], sparteine- [7], mersicarpine- [8], batzelladine- [9], fuligocandin- [10] and vitamin B12-derivatives [11] were prepared with the aid of sulfide contraction steps. Pharmaceutically important substances, such as methylphenidat [12] or the marine neurotoxin hemibrevetoxin

Nano copper oxide catalyzed synthesis of symmetrical diaryl sulfides under ligand free conditions

• K. Harsha Vardhan Reddy,
• V. Prakash Reddy,
• A. Ashwan Kumar,
• G. Kranthi and
• Y.V.D. Nageswar

Beilstein J. Org. Chem. 2011, 7, 886–891, doi:10.3762/bjoc.7.101

• decrease in the yield of the diaryl sulfide (Table 3, entries 12 and 13) was observed. Under these reaction conditions, various hetero aromatic iodides were reacted with potassium thiocyanate and gave the corresponding diaryl sulfides in appreciable yields (Table 3, entries 15, 16 and 17). In case of the

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• epoxide ring opening of 18 with potassium hydrogen sulfide (Scheme 7) [18]. Epoxide ring opening by a sulfur nucleophile was also employed as the key step in the synthesis of (+)-BE-52440A (22) [22] (Scheme 8). Dimerisation of nanaomycin derivative 21 through a bridging sulfide involves a double

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• 3e was prepared in 86% yield by hydrogenation of the corresponding 4-methylenetetrahydropyran 6e in the presence of ZnBr2 to prevent reductive dechlorination (Scheme 7) [46]. Attempts to use diphenyl sulfide as a catalyst poison [47] resulted only in recovery of the starting material. Wittig

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• examples of such a reaction on proteins. This led to a new benchmark in substrate complexity for cross-metathesis and expanded the potential of olefin metathesis for other applications in chemical biology. The enhanced reactivity of allyl sulfide, along with earlier reports of a similar effect by allylic

• substrates [27][28]. The effect of other allylic chalcogens in olefin metathesis Allyl sulfides are privileged substrates in olefin metathesis While there are many examples of allylic alcohols and ethers in metathesis, examples with allyl sulfide substrates were until recently noticeably few. This is

• amino acids with allyl alcohol mediated by catalyst 4 was investigated. Unexpectedly, S-allylcysteine derivative 21a was the only substrate that afforded a synthetically useful amount of CM product, whereas the reaction of the all carbon analogue homoallylglycine (20) and sulfide derivatives, S-butenyl

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• significant. The reaction is carried out by heating a mixture of aryl trichloromethyl sulfide with an excess of SbF3 in the absence of a solvent. For industrial processes, dry hydrogen fluoride is used as the fluorinating agent (Scheme 1). The presence of halogen atoms and electron-withdrawing groups such as

• longer perfluoroalkyl sulfides because the required aryl perchloroalkyl sulfide precursors are not easily accessible [57][58]. However, pentafluoroethyl ethers of various thiophenols (or phenols) can be obtained by the more sequential process as shown in Scheme 2 [59]. Use of mixed (Cl/F

• ) polyhalogenofluoro alkanes as partial fluorinated alkylating agents generates the corresponding sulfides which are appropriate precursors for subsequent conversion to perfluoroalkyl thioethers. For example, α,α-difluoro polyhalogenoalkyl sulfides and α,α-dichlorotrifluoroethyl sulfide can be obtained by reaction of

Synthesis of the fluorescent amino acid rac-(7-hydroxycoumarin-4-yl)ethylglycine

• Manfred Braun and
• Torsten Dittrich

Beilstein J. Org. Chem. 2010, 6, No. 69, doi:10.3762/bjoc.6.69

• acetonedicarboxylate. First, the acid 2 was reduced to the alcohol 3 with borane. The protocol described in the literature [12] was modified, and the reducing agent borane–tetrahydrofuran replaced by the less expensive borane–dimethyl sulfide. This also led to a slight increase in yield (59%). For the planned

• 0 °C. Through the dropping funnel, a 10 M solution of borane–dimethyl sulfide (12 mL, 120 mmol) in THF, diluted with 100 mL of dry THF was added dropwise over 60 min at 0 °C. Stirring was continued at r. t. for 24 h. After cooling to 0 °C, water (10 mL) was cautiously added. The mixture was

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• electron-enriched arenes. Reagent 3 reacted with sodium p-nitrothiophenolate to give the corresponding trifluoromethyl sulfide 4 in 65% yield (Scheme 1). The substitution proceeded smoothly although electron-donating substituents on 3 partially neutralize the positive charge on the sulfur atom and thus

• electrophilic one [27]. This method opens up the possibility for the preparation of various reagents with electron-withdrawing substituents even in the para-position of aromatic compounds. The difluorosulfurane 26, obtained from the corresponding sulfide by treatment with xenon difluoride, was reacted first

• ). Interestingly, the method was developed for the synthesis of heteroaromatic diarylsulfonium salts. Thus, p-nitrophenyl trifluoromethyl sulfide was reacted first with xenon difluoride in the absence of solvent and then with boron trifluoride. The addition of an electron-rich heterocycle gave products 28 and 29

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• exocyclic olefin was then converted to the corresponding ketone through ozonolysis. The ozonide and N-oxide were reduced with dimethyl sulfide at the end of the reaction. Using the Gardner protocol [96] to hydroxylate the alpha position of the resultant ketone failed to give any α-ketol, but instead

Synthesis and enzymatic evaluation of 2- and 4-aminothiazole- based inhibitors of neuronal nitric oxide synthase

• Graham R. Lawton,
• Haitao Ji,
• Pavel Martásek,
• Linda J. Roman and
• Richard B. Silverman

Beilstein J. Org. Chem. 2009, 5, No. 28, doi:10.3762/bjoc.5.28

• in Scheme 4. Treatment of acetonitrile with LDA followed by addition of epoxide 5 gave trans-alcohol 24 [14]. The nitrile group was converted to a thioamide using ammonium sulfide [15]. The thioamide was condensed with either ethyl bromopyruvate or an epoxide (30) [16]. Condensation produces an

Enantiospecific synthesis of [2.2]paracyclophane- 4-thiol and derivatives

• Gareth J. Rowlands and
• Richard J. Seacome

Beilstein J. Org. Chem. 2009, 5, No. 9, doi:10.3762/bjoc.5.9

• was investigated (Scheme 1). The first step, the reduction of (Sp,RS)-5 to sulfide (Sp)-6, proved the most problematic; use of a large excess of trichlorosilane and triethylamine resulted in deoxygenation in moderate yield after recrystallisation [40]. By comparison, reduction of the less hindered

• amino sulfide (Rp)-9. Simultaneous sulfide deprotection and thiazole formation was achieved by treating (Rp)-9 with concentrated hydrochloric acid, paraformaldehyde and pyridine [48]. Although the yield of (Rp)-10 is not yet satisfactory, it shows the potential of our methodology for the formation of

Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): Efficient formation of products derived from aryl radicals

• Mohan Mahesh,
• John A. Murphy,
• Franck LeStrat and
• Hans Peter Wessel

Beilstein J. Org. Chem. 2009, 5, No. 1, doi:10.3762/bjoc.5.1

• the radical chemistry. One way to achieve clean termination of the radical process would be by providing a radical leaving group adjacent to the cyclised radical 19. Appropriate groups might be sulfide, sulfoxide and sulfonyl groups [64][65]. Accordingly, arenediazonium salts 31a–d were prepared

• like a sulfide, sulfoxide or sulfone is necessary for the self-termination of the 5-exo-trig radical cyclization reactions to avoid competing intermolecular radical side-reactions. The TDAE-mediated radical-based addition-elimination route for the construction of indole ring systems warranted anhydrous

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• the sodium enolate of 59 to afford the main structure 60. Oxidation of the sulfide 60 followed by thermal elimination and deprotection completed the total synthesis of solamin (57). The data of the synthetic 57 were identical to those of an authentic sample [38]. In their total synthesis of solamin

• alkylate the sodium enolate of lactone 15 to afford 70. Oxidation of the sulfide 70 followed by thermal elimination and finally removal of the two silyl protective groups gave solamin (57). But after careful comparison the configuration of the OH-group in C13 between the literature for isolation [38] and

• 298 with the propargylic alcohol 297 proceeded smoothly to produce the skeleton 299. The enyne functional group was reduced selectively and final global deprotection with BF3·Et2O in dimethyl sulfide afforded 294 as a colorless wax. The spectroscopic data for synthetic 294 (1H NMR, 13C NMR, IR, MS

Efficient 1,4-addition of α-substituted fluoro(phenylsulfonyl)methane derivatives to α,β-unsaturated compounds

• G. K. Surya Prakash,
• Xiaoming Zhao,
• Sujith Chacko,
• Fang Wang,
• Habiba Vaghoo and
• George A. Olah

Beilstein J. Org. Chem. 2008, 4, No. 17, doi:10.3762/bjoc.4.17

• . We first began with the preparation of nitro, cyano, ester, or acetyl-substituted (phenylsulfonyl)methanes from the corresponding (phenylthio)methane derivatives, the precursors of α-substituted fluoro(phenylsulfonyl)methane derivatives. Oxidation of (nitromethyl)(phenyl)sulfide with aqueous hydrogen

Analogues of amphibian alkaloids: total synthesis of (5R,8S,8aS)-(−)-8-methyl- 5-pentyloctahydroindolizine (8-epi-indolizidine 209B) and [(1S,4R,9aS)-(−)-4-pentyloctahydro- 2H-quinolizin- 1-yl]methanol

• Joseph P. Michael,
• Claudia Accone,
• Charles B. de Koning and
• Christiaan W. van der Westhuyzen

Beilstein J. Org. Chem. 2008, 4, No. 5, doi:10.1186/1860-5397-4-5

• -benzyl-1-phenylethylamine, was converted into the primary amine (−)-15 and thence in several steps into the thiolactam (+)-16. Eschenmoser sulfide contraction [22][23] with ethyl bromoacetate yielded the key enaminone intermediate (+)-17, chemoselective reduction of the saturated ester of which produced

• lactam (+)-26 was troublesome, giving at best a yield of 52% when performed with sodium hydride and tetrabutylammonium iodide in N,N-dimethylformamide. An effortless thionation of 26 with Lawesson's reagent in boiling toluene produced the thiolactam (+)-27 in 92% yield. Eschenmoser sulfide contraction

The use of chiral lithium amides in the desymmetrisation of N-trialkylsilyl dimethyl sulfoximines

• Matthew J. McGrath and
• Carsten Bolm

Beilstein J. Org. Chem. 2007, 3, No. 33, doi:10.1186/1860-5397-3-33

• , Entry 1), affording 2c in high yield and improved ee (86% yield, 70% ee, Table 2, Entry 2). When N-(diphenylmethylene)-toluenesulfonamide was used as electrophile the sulfoximine adduct 2d was obtained in low yield and ee (Table 2, Entry 3). In contrast, diphenyl disulfide gave sulfide 2e in accepee but

A convenient allylsilane- N-acyliminium route toward indolizidine and quinolizidine alkaloids

• Roland Remuson

Beilstein J. Org. Chem. 2007, 3, No. 32, doi:10.1186/1860-5397-3-32

• group followed by the simultaneous reduction of the two carbonyl groups of keto lactams 43a and 43b. Thus, treatment of 42a with ozone then with dimethyl sulfide afforded the expected keto lactam 43a in 91% yield. Ozonolysis of 42b led to keto lactam 43b in 63% yield. Reduction of 43a with lithium

Chiral trimethylsilylated C₂-symmetrical diamines as phosphorous derivatizing agents for the determination of the enantiomeric excess of chiral alcohols by ¹H NMR

• Anne-Sophie Chauvin and
• Alexandre Alexakis

Beilstein J. Org. Chem. 2006, 2, No. 6, doi:10.1186/1860-5397-2-6

• spectrum in the -0.4↔0.6 ppm region of 2-(2-isopropyl-5-methyl-cyclohexyloxy)-1,3-bis-trimethylsilanylmethyl-octahydro-benzo [1,3,2] diazaphosphole 2-sulfide. C2-diamines used in this study. Synthesis of diamines 1 and 2. Synthesis of diamine 3. 31P chemical shift differences Δδ (ppm) of some butan-2-ol P

Reagent controlled addition of chiral sulfur ylides to chiral aldehydes

• Varinder K. Aggarwal and
• Jie Bi

Beilstein J. Org. Chem. 2005, 1, No. 4, doi:10.1186/1860-5397-1-4

• clearly shown by sulfide 2 could be exploited in reactions with chiral aldehydes and to what extent it might dominate over substrate control (Scheme 2).[3] Again C1 stereochemistry should be controlled by ylide conformation, face selectivity, degree of reversibility in anti betaine formation, and is not

• the vicinal coupling constants (cis >trans). Assignment of the two trans diastereomers has been based on (i) the model for addition of the two enantiomers of the chiral sulfide to aldehydes and (ii) comparison of the H2-H3 coupling constants found for the major and minor diastereomers of the glycidic