Cobalt-catalyzed nucleophilic addition of the allylic C(sp³)–H bond of simple alkenes to ketones

• Tsuyoshi Mita,
• Masashi Uchiyama,
• Kenichi Michigami and
• Yoshihiro Sato

Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176

• toluene, 0.15 mL, 0.3 mmol, 1.5 equiv) was added. The dark green solution was stirred for another 1 minute, and then alkene 1 (0.6 mmol, 3.0 equiv) was added followed by the addition of ketone 2 (0.2 mmol, 1.0 equiv). The resulting mixture was stirred at 90 ºC for 16 h. After cooling the mixture to 0 ºC

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• ], aminofluorination [29], dioxygenation [30][31], and diamination [32][33] of alkenes could be achieved. Especially, when a nucleophile-tethered alkene is used, a cyclization product was obtained [34][35], although, stoichiometric amounts of hypervalent iodine(III) reagents were required. Due to the metal-like

• environment at the iodine center. Mechanistically, the iodine(III) 16 is activated by triflic acid generating a free coordination site at the iodine(III) center [54]. The coordination of the alkene to the activated iodine(III) center generates the required prochiral face differentiation and the nucleophilic

• of substrates bearing either two or four methylene groups between the alkene and sulfonamide failed to provide the fluoroheterocycles. Difluorination of alkenes Hara and co-workers reported a vicinal difluorination of unactivated alkenes in the presence of stoichiometric amounts of difluoro

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• , hemithioacetal, various thioesters, thiocarbamate and isothiocyanate. This review article focuses on β-hydroxy sulfides and analogs; their presence in natural products, general protocols for their synthesis, and examples of their application in target oriented synthesis. Keywords: alkene thiofunctionalization

• thiols to give various β-hydroxy sulfides in good yields (Scheme 1) [20]. Both aryl and alkylthiols were found to be capable of opening the epoxide ring under the reaction conditions, and with respect to the epoxides, cycloalkane, alkene and 1-substituted alkene oxides were all amenable to the reaction

• alkene to form radical 87. This intermediate undergoes oxidation followed by decomposition to provide the alkoxy radical intermediate 88, which then affords the β-hydroxy sulfide 81 upon protonation. The considerably stronger S–S bonds of the dialkyl disulfides and the lower stability of the expected

Visible light-mediated difluoroalkylation of electron-deficient alkenes

• Vyacheslav I. Supranovich,
• Vitalij V. Levin,
• Marina I. Struchkova,
• Jinbo Hu and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2018, 14, 1637–1641, doi:10.3762/bjoc.14.139

• decreased reactivity of the sulfone double bond toward fluorinated radicals. In this case, two equivalents of the alkene have to be used to achieve good yields of products 3t,u. It should also be pointed out that the reaction tolerates aromatic bromide substituents (products 3b,c,n,o), a boryl fragment

• hydrogen and as a trigger for the generation of free radicals mediated by visible light. Difluoroalkylation of alkenes. Isolated yields are shown. a2 equiv of the alkene were used. Fluoroalkylation of alkenes. Proposed mechanism. Optimization studies. Supporting Information Supporting Information File 220

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• the catalyst thereby leading to the expected products 41 with yields in the 26–75% range (Scheme 13) [48]. Interestingly, an alkene diazidation reaction is observed by simply performing the transformation in DMSO and replacing Cu(OTf)2 by CuI as the catalyst. Enamides 42 are also relevant substrates

• occur with chlorobenziodoxolone 45 [51]. Oxychlorinated, dichlorinated, azidochlorinated and chlorothiocyanated products can thus be isolated mostly from styrenyl substrates. However, the treatment of 45 with tetra-butylammonium iodide followed by the addition of an alkene leads to the formation of

• be resubmitted to the cyclization conditions in the presence of a different terminal alkyne, or an activated alkene. The same authors have then showed that the reaction of cyclic diaryl-λ3-iodanes in the presence of internal alkynes and the catalytic system Pd(OAc)2-PCy3 affords functionalized

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• a carbon–carbon bond-forming reaction occurring between the α-position of an activated alkene and a carbon electrophile such as an aldehyde. Employing a nucleophilic organocatalyst [26], such as a tertiary amine or a phosphine, this simple reaction provides densely functionalized products, such as α

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• last 25 years. This review highlights the contribution of different chiral hypervalent iodine reagents in diverse asymmetric conversions. Keywords: alkene functionalization; asymmetric synthesis; hypervalent iodine; organocatalysis; oxidation; Introduction It is more than one century ago since the

• ) [31]. A summary of chiral hypervalent iodine reagents used in the asymmetric oxidation of sulfides is sketched below (Scheme 2). Asymmetric oxidative dearomatization, alkene functionalization and rearrangement strategy Oxidative dearomatization Asymmetric oxidative dearomatizations and the use of

• phenol dearomatization, leading to the formation of cyclodimerization products 43 with high enantioselectivity (up to 94% ee, Scheme 8 lower part). Alkene functionalization Nearly simultaneously to Ishihara’s work, Fujita et al. reported on the modification of their previously synthesized non C2

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• . Thus, the conjugate 11 was chosen for further development as an anti-lung cancer therapeutic. In the similar fashion, the same group investigated the correlation between DNA binding and antibacterial activity shown by these novel distamycin alkene-containing analogs (MGB-BP-3, 12 and 13, Figure 4

• . Suckling et al. designed a set of 31 Strathclyde minor groove binders (S-MGBs), derived from distamycin, by varying the head groups (amidine, amide, or alkene), heterocyclic building blocks and their alkyl substituents and the basicity of the C-terminal tail group in order to investigate their antimalarial

• activity against a chloroquine sensitive (3D7) and resistant (Dd2) strain of Plasmodium falciparum [100]. Conjugates with an alkene link between the two N-terminal building blocks and a C-alkylthiazole moiety appeared to the most active among others with IC50 values in the range of 30–500 nM. The same

Hypervalent iodine-mediated Ritter-type amidation of terminal alkenes: The synthesis of isoxazoline and pyrazoline cores

• Sang Won Park,
• Soong-Hyun Kim,
• Jaeyoung Song,
• Ga Young Park,
• Darong Kim,
• Tae-Gyu Nam and
• Ki Bum Hong

Beilstein J. Org. Chem. 2018, 14, 1028–1033, doi:10.3762/bjoc.14.89

• alkene functionalization utilizing a PhI(OAc)2 ((diacetoxyiodo)benzene, PIDA)/Lewis acid combination in order to access isoxazoline and pyrazoline cores. Based on allyl ketone oximes and allyl ketone tosylhydrazones, we have developed an alkene oxyamidation and amido-amidation protocol en route to

• unactivated olefins provides a rapid construction of different heterocycles [16][17]. More specifically, the formation of isoxazoline and pyrazoline cores via alkene heterofunctionalization of allyl ketone oximes and/or allyl ketone tosylhydrazones has been well documented [18][19][20][21][22]. For example

• [23][24][25][26][27]. Results and Discussion As depicted in Scheme 1, we have previously reported an inter-/intramolecular alkene diamination using either N-iodosuccinimide (NIS) or a phenyliodine diacetate (PIDA)/halide additive combination [28][29][30]. Vinylanilines and vinylaminopyridines in

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• electrolysis was stopped after the total consumption of 1a (1.5 F), a mixture of products was obtained (Scheme 5 and Table 1, entry 4). In particular, a large amount (48%) of the brominated alkyne 3a was isolated, along with traces of hydrogenated alkene 4a. In order to confirm the effect of the presence of a

• terminated as the current flow stopped very early [30]. When a silver cathode was used, a good yield of desired alkyne 2a was obtained (72%), along with a small amount of hydrogenated alkene 4a (6%). In order to increase the yield of alkyne 2a (and as 2a reduction potential is much more negative, vide infra

• ), we carried out a cathodic reduction of 1a on a silver cathode at the second reduction wave potential (Table 1, entry 10). In this last case, the selectivity of the reaction dropped and a notable amount of hydrogenated alkene 4a was obtained (15%), along with a lower yield of alkyne 2a (65%). The

Anodic oxidation of bisamides from diaminoalkanes by constant current electrolysis

• Tatiana Golub and
• James Y. Becker

Beilstein J. Org. Chem. 2018, 14, 861–868, doi:10.3762/bjoc.14.72

• suggested that the analysis will be done immediately after terminating the electrolysis. Characterization of products See Supporting Information File 1 for spectral data and copies of 1H and 13C NMR spectra. Anodic oxidation of amides. Anodic oxidation of an amide in the presence of alkene. Intramolecular

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• ; however, repeating the reaction under reflux conditions gave 3a as a mixture of E/Z alkenes in 58% yield (Table 1, entries 1 and 2). The reaction was entirely selective for the terminal alkene, with none of 3a’ being observed. Toluene, chlorobenzene, DMF and DCE were also tested as reaction solvents, but

• -dichlorides 3a and 3b in excellent yield, favouring the Z-alkene (Scheme 3). The 4-bromo and 2-, 3- or 4-chloro derivatives 2c–f led to 3c–f in only moderate yield, with the mass balance of chlorinated materials being made up by the regioisomeric vicinal-dichloroination products 3c’–f’ (compare with 3a

• ’, Scheme 2) [30]. The p-anisyl derivative 2g was also viable in the reaction, giving 3g in 64% yield, as were the 1- and 2-naphthylallenes (2h and 2i), which gave the desired dichlorides 3h and 3i in 93% and 78% yield. In each case, preference for forming the Z-alkene was observed, with selectivities

Electrochemical Corey–Winter reaction. Reduction of thiocarbonates in aqueous methanol media and application to the synthesis of a naturally occurring α-pyrone

• Ernesto Emmanuel López-López,
• José Alvano Pérez-Bautista,
• Fernando Sartillo-Piscil and
• Bernardo A. Frontana-Uribe

Beilstein J. Org. Chem. 2018, 14, 547–552, doi:10.3762/bjoc.14.41

• Trichoderma viride [8]. This fact let us to conclude that the thiocarbonate group was reduced selectively to the trans-alkene in a Corey–Winter-type reaction [2][3] giving the targeted structure 5 in 95% isolated yield (Scheme 4, Table 1, entry 1). The reaction occurred stereoselectively with no trace of cis

• -alkene isomer. The use of graphite electrodes instead of the reticulated vitreous carbon eroded the chemical yield to 80% (Table 1, entry 2). Cyclic voltammetry analysis of 4 showed a second reduction peak at −1.6 V (Figure 1), a value that agrees with that for reduction of the α,β-unsaturated ester

• . The same potential controlled electrolysis protocol used for 4 was applied to the alkene thiocarbonate derivative 6, but reducing it at −1.2 V vs Ag/AgCl, and likewise, quantitative chemical yield of the corresponding E-alkene 9 was obtained (Table 1, entry 4). Also, the CCE of 6, using the same

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• SF5X (X = Cl, Br, SF5) across π-bonds. The unconventional conditions usually required were overcome by Dolbier’s elegant triethylborane initiation [21]. Recently, the radical arylation of a SF5-substituted alkene was realized in order to gain access to SF5-containing dihydrobenzofurans and indolines

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• concept [32] (Scheme 4b) [34]. They first introduced alkene moieties to the chemically inert lignin structure by esterification of the hydroxy groups of lignin with 4-pentenoic acid. Subsequent radical thiol–ene reaction with aliphatic thiols, using [Ru(bpy]3Cl2 as photocatalyst and p-toluidine as redox

• radical anion then deprotonates the thiyl radical cation. Subsequent addition to the alkene yields the anti-Markovnikov radical intermediate. Radical addition to dioxygen leads finally to the β-ketosulfide, which subsequently is oxidized by the in situ generated hydrogen peroxide radical to the respective

• sulfenylated dienes by dehydration. A series of aryl thiols with different steric and electronic properties give high yields of the thiol–yne products. Noteworthy is the high E-selectivity of the resulting alkene. Dependent on the substitution pattern of the aryl thiol a ratio up to 60:1 was observed due to

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• Becquerel, 67087 Strasbourg, France 10.3762/bjoc.13.281 Abstract The acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicylic alkene using alcohol nucleophiles were investigated. Although this acid-catalyzed ring-opening reaction did not cleave the cyclopropane unit as planned, this

• to modify selected components of the molecule to create vastly different products. 3-Aza-2-oxabicyclic alkenes are generally modified in one of four ways (Scheme 1). One of the most interesting manipulations of 3-aza-2-oxabicyclic alkenes is the modification of the alkene component. The manipulation

• of the olefin can lead to a wide variety of products often in a single step, which is synthetically useful to create many highly substituted products with different stereochemical outcomes (Scheme 2). There are many reported examples in the literature of the modification of the alkene component which

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• alkene was cis-configured, its introduction was possible from the start (Scheme 3). Hence, following literature procedures [24][25][26], the reaction of cis-1 with 2,2-dimethoxypropane and subsequent epoxidation led to 7. However, epoxide opening with Et3N·3HF was accompanied by acetonide rearrangement

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• -cyanotrifluoromethylations [22] of alkenes under photoredox catalysis. These reactions proceeded through a formyl or a cyano group migration triggered by the addition of the trifluoromethyl radical onto the alkene moiety. Both methodologies were developed using Togni’s hypervalent iodine reagent as the CF3 source, but it

• , no dehydrochlorination reaction was mentioned for any of the studied substrates. The reaction plausibly proceeded through a mechanism similar to the one previously proposed by Kamigata and co-workers. The SET generated CF3 radical attacked preferentially the less hindered carbon of the alkene to

• transferred as a whole onto radical 26. However, this bonding interaction appeared to be weak enough to possibly be destabilised in the presence of a donor atom on the alkene substrate, thus favouring SO2 extrusion and chlorotrifluoromethylation. The obtained CF3-containing sulfonyl chloride derivatives could

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• (Scheme 11) [30]. Amino- and azotrifluoromethylation of alkenes: Alkene trifluoromethylation was applied to the construction of indole, pyrazole and pyridazinone moieties via a multicomponent cascade reaction developed by Antonchick and Matcha in 2014 [31]. The method was based on the reaction between

• simple alkenes, sodium triflinate and diazonium salts. The CF3 radical was produced from CF3SO2Na by oxidation with H2O2 in the presence of silver nitrate. Then, CF3• was added to the terminal position of the alkene to give radical 26 that was trapped by the arenediazonium salt to form the radical cation

• 27, which was reduced into 28 prior to be converted into nitrogen heterocycles via [1,3]-hydride shift and cyclisation steps (Scheme 12). The reaction was regioselective and had a broad scope. This application of alkene trifluoromethylation provided a convenient entry to trifluoromethylated nitrogen

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• the alkene [39]. An interesting pathway of generating ylides from vinylphosphonium salts turned out to be the reaction of the latter compounds with Grignard reagents in the presence of CuBr·H2O or CuBr·Ag2CO3 (Scheme 24). The subsequent Wittig reaction allowed to obtain substituted alkenes 34 in a

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• oxazolidinone derivative 31 was first achieved with an excellent yield (88%) and diastereoselectivity (de > 95%). The chiral auxiliary was then removed and the free alcohol was oxidized to the corresponding aldehyde 32. Alkene 33 was then obtained after olefination of 32 with low selectivity ((Z):(E) = 64:36

• fluorenylmethyloxycarbonyl group. Oxidation of the remaining alcohol to the corresponding carboxylic acid provided the dipeptide isostere 35. Couve-Bonnaire and co-workers developed the preparation of (E)-monofluoroalkene dipeptide isosteres towards an intramolecular ring-closure metathesis (Scheme 8) [35]. The bis-alkene

• (Cbz)-ψ[(Z)-CF=CH]-Lys(Cbz) [49] and Fmoc-Orn(Ns)-ψ[(Z)-CF=CH]-Nal were obtained [50]. Fujii and co-workers also worked on the stereoselective synthesis of (E)-monofluoroalkenes (Scheme 17) [51]. To obtain a good selectivity towards the (E)-alkene, they relied on the copper-mediated reduction and the α

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• alkene did not interfere with the reaction efficiency, providing 3l in 83% yield. The reaction was not restricted to aromatic alkenes, enamide was also applicable to the reaction and afforded 3m in 61% yield. To demonstrate the generality of this method further, reactions of alkenes with various

• successfully employed to couple with a conjugated alkene and afforded the corresponding products 4d and 4h in good yields. The current cross coupling was also applicable to the secondary difluoroalkylated alkyl halides as demonstrated by the representative reaction of secondary ethyl 2,2-difluoro-2-iodoacetate

• begins with the reaction of [PdLn(0)] with secondary trifluoromethylated 2 via a SET pathway to generate alkyl radical B. B subsequently reacts with alkene to produce new radical species D, which then recombines with [LnPd(I)Br] C to give the key palladium-complex E. Finally, a β-hydride elimination

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• fluoride, then deoxyfluorination). We therefore sought to apply O’Hagan’s method to the target 6b (Scheme 3, boxed). Accordingly, the enantiopure allylic alcohol 27 [35] was extended through a cross-metathesis reaction to deliver the disubstituted alkene 30 (Scheme 3). Compound 30 became the substrate for

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• it was recently reviewed [235]. 7. Preparation of phosphonic acid by oxidation of phosphinic acid Phosphinic acid derivatives (also identified as phosphonous acid) are prepared by reaction of hypophosphorous acid (Figure 35) on alkene or alkyne (hydrophosphonation) [236], by its addition on aldehyde

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• conventional steps viz. HWE-type olefination leading to the unsaturated ester 5, saturation of the double bond in the latter to 6, reduction of the ester moiety in 6 to the alcohol 7 followed by its oxidation. The aldehyde 8 thus obtained was subjected to a Wittig olefination to obtain the desired alkene 9 in