A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• further reactions. Reaction of N-chloramine with alkene Initially our study tested the reaction of N-chloromorpholine (16) to styrene (13) varying Cu catalyst loading and a range of temperatures. The anti-Markovnikov addition product was observed with 10% CuI catalyst loading, at ambient temperature

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• -containing oxidative systems with the addition of various nucleophiles have been published, all of these processes have common mechanism and the same regioselectivity. The free-radical approach developed in the present work affords the opposite (anti-Markovnikov) regioselectivity of the addition to the

• for anti-Markovnikov type regioselectivity of C–O and C–I bond formation. Electrochemical mechanistic studies based on cyclic voltammetry (CV) data confirm proposed reaction mechanism. Possible ways of using the obtained iodo-oxyimidated products via substitution of iodine atom were demonstrated

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

• ]. The thiyl radical was generated as reactive key intermediate from a variety of thiols by photooxidation using [Ru(bpz)3](PF6)2. Aliphatic and aromatic thiols react with aliphatic and aromatic alkenes and alkynes in high to excellent yields to the anti-Markovnikov addition adducts. However, an excess

• 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

• . Radical addition to the alkyne leads to the anti-Markovnikov adduct via the more stable secondary radical intermediate. As alkyne 2-methyl-3-butyn-2-ol was selected, which is easily prepared from acetylene and acetone on large scale and the respective thiol–yne adducts can be converted into valuable

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

• chalcone gave low regioselectivities with mixed Markovnikov and anti-Markovnikov products. The CF3 radical is electrophilic in nature and, as such, not prone to readily react with electron-deficient alkenes. Nevertheless, Lefebvre, Hoffmann and Rueping reported that N-substituted maleimides, maleic

• -Markovnikov selectivity. Notably, styrene failed to react under these conditions. A selection of α,β-unsaturated electron-withdrawing motifs that included a sulfone, esters, an amide, and a ketone were investigated for the first time and the β-addition products were obtained regioselectively in moderate to

Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate

• Clément Ghiazza,
• Anis Tlili and
• Thierry Billard

Beilstein J. Org. Chem. 2017, 13, 2626–2630, doi:10.3762/bjoc.13.260

• . Further, a high regioselectivity is observed but, surprisingly, the anti-Markovnikov regioisomers were obtained. The stereochemistry and regiochemistry were confirmed thanks to the X-ray structure of compound 3a (Figure 1). From a mechanistic point of view, the reaction starts certainly with the

Is the tungsten(IV) complex (NEt₄)₂[WO(mnt)₂] a functional analogue of acetylene hydratase?

• Matthias Schreyer and
• Lukas Hintermann

Beilstein J. Org. Chem. 2017, 13, 2332–2339, doi:10.3762/bjoc.13.230

• absence of a satisfactory mechanistic proposal for the hydration reaction, we considered the possibility of a metal–vinylidene type activation mode, as it is well established for ruthenium-based alkyne hydration catalysts with anti-Markovnikov regioselectivity. To validate the hypothesis, the

• hydration (Scheme 2a), whereas alkynol cycloisomerization proceeds via rearrangement to a tungsten vinylidene complex and addition of the alcohol hydroxy group to the vinylidene α-carbon [18]. The vinylidene mechanism is related to that of ruthenium-catalyzed anti-Markovnikov hydration of terminal alkynes

• -workers [9]. Experimentally, the vinylidene mechanism is revealed in the hydration of a terminal alkyne by producing an aldehyde (anti-Markovnikov type addition) as opposed to a methyl ketone (Markovnikov type addition; typical for π-activation mechanisms) [18]. Hydration reactions of 1 involving higher

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• -dimethylacryloyl chloride and pyridine provided 12 in good yield (Scheme 5). The acid-catalysed reaction with 12 was predicted to proceed via initial formation of the corresponding tertiary alcohol involving a Markovnikov addition, before cyclisation as with 10. Indeed, cyclisation product 13 (see Supporting

Aerobic addition of secondary phosphine oxides to vinyl sulfides: a shortcut to 1-hydroxy-2-(organosulfanyl)ethyl(diorganyl)phosphine oxides

• Svetlana F. Malysheva,
• Alexander V. Artem’ev,
• Nina K. Gusarova,
• Nataliya A. Belogorlova,
• Alexander I. Albanov,
• C. W. Liu and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2015, 11, 1985–1990, doi:10.3762/bjoc.11.214

• addition of P–H species to the C=C bonds readily proceeds in the absence of any catalyst or initiator (Scheme 1). The reactions occur under mild solvent-free conditions (70–80 °C, inert atmosphere, 3–15 h) to chemo- and regioselectively furnish the anti-Markovnikov adducts in excellent yields (up to 99

• (diorganyl)phosphine oxides 3a–h in high yields (Table 1). The 10% excess of 2a–c relative to 1a–f is found to be optimal since the equimolar ratio of the reactants leads to incomplete conversion of the secondary phosphine oxides. Importantly, under these conditions, the expected [30] anti-Markovnikov

• exclusively the anti-Markovnikov adducts (Scheme 2). On the other hand, vinyl ethers and vinyl selenides (congeners of vinyl sulfides) were found to react with phosphine oxide 1a at 80 °C for about 30 and 20 h, respectively, to deliver difficult-to-separate mixtures of organophosphorus compounds (31P NMR). To

Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

• Biljana M. Šmit,
• Radoslav Z. Pavlović,
• Dejan A. Milenković and
• Zoran S. Marković

Beilstein J. Org. Chem. 2015, 11, 1865–1875, doi:10.3762/bjoc.11.200

• -alkenylhydantoin is supposed to be reversible, and leads to the formation of two theoretically possible pairs of regioisomeric intermediates, (S,R/S,S)-INT1 (Markovnikov products) and (S,R/S,S)-INT1’ (anti-Markovnikov products) (Scheme 1). A similar mechanism was proposed earlier for cyclofunctionalization of

• olefinic urethanes [36]. The formation of addition products as intermediates in the second step was proposed after monitoring of the reaction by using 1H NMR spectroscopy (Figure 1). Also, in this experiment a regioselective formation of Markovnikov-type products of the addition of selenium reagent to the

• proton of (S,R)-INT1’ and (S,S)-INT1’ are notably larger (5.0 and 4.8 ppm, respectively) (Supporting Information File 1, Table S1). This finding indicates that the (S,R/S,S)-INT1 (Markovnikov aduct) is formed as an intermediate of the examined reaction. On the basis of the calculated 1H chemical shifts

Photocatalytic nucleophilic addition of alcohols to styrenes in Markovnikov and anti-Markovnikov orientation

• Martin Weiser,
• Sergej Hermann,
• Alexander Penner and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2015, 11, 568–575, doi:10.3762/bjoc.11.62

• ) and styrene (6) into the Markovnikov- and anti-Markovnikov-type products was selectively achieved with 1-(N,N-dimethylamino)pyrene (Py) and 1,7-dicyanoperylene-3,4:9,10-tetracarboxylic acid bisimide (PDI) as photoredox catalysts. The regioselectivity was controlled by the photocatalyst. For the

• reductive mode towards the Markovnikov-type regioselectivity, Py was applied as photocatalyst and triethylamine as electron shuttle. This approach was also used for intramolecular additions. For the oxidative mode towards the anti-Markovnikov-type regioselectivety, PDI was applied together with Ph–SH as

• , Maroulis et al. [17][18]. They demonstrated that electron-rich naphthalenes are able to photoinitiate methanol additions to olefins into the Markovnikov orientation and proposed an oxidative electron transfer mechanism for this process [17]. Complementarily, electron-poor naphthalenes yielded the anti

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• on the regioselectivity of the reaction, the addition of P–H to the unsaturated bond results in the formation of different products 43 (Scheme 13). The product that results from the Markovnikov addition of P–H corresponds to the α-adduct and the anti-Markovnikov addition is referred to as the β

• thermal activation [75][76], through the use of radical initiators (AIBN) [77][78][79][80][81][82] or photochemically by irradiation with UV or visible light [22][83][84][85]. Most of these reactions give anti-Markovnikov products. The hydrophosphination of activated alkenes (e.g., Michael acceptors) has

• ] or AIBN radical [77][78][83][235][236]) or transition metal activation. Depending on the regioselectivity of the procedure, the addition of P–H to the triple bond results in the formation of two regioisomers (Scheme 36). The product that results from the Markovnikov addition of P–H corresponds to the

Silica: An efficient catalyst for one-pot regioselective synthesis of dithioethers

• Samir Kundu,
• Babli Roy and
• Basudeb Basu

Beilstein J. Org. Chem. 2014, 10, 26–33, doi:10.3762/bjoc.10.5

• by silica NPs, where a single example of a reaction of an allyl bromide and excess benzenethiol was studied [41][42]. The reaction was carried out in the presence of silica NPs and water, and they isolated 1,3-dithioether by an anti-Markovnikov addition. However, there is no report on the metal-free

• hydrothiolation of allylic substrates in a Markovnikov fashion to afford 1,2-dithioethers in one-pot reactions. In this paper, we wish to report our investigations on the reaction of allyl halides with excess thiols promoted by silica gel, which finally constitutes distinct protocols for one-pot, solvent-free

• that indeed led to the formation of 1,2-dithioether in 91% yield. On the other hand, if silica gel moistened with a few drops of water was used for the same reaction, the regioselective anti-Markovnikov addition product, i.e., 1,3-dithioether, (1-(3-(phenylthio)propylthio)benzene) was obtained in 83

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• works, Yang and He reported on the Ph3PAuOTf assisted Markovnikov-like addition of phenols and carboxylic acids to C=C under mild reaction conditions (Scheme 1) [27]. Electron-rich and electron-poor phenols reacted smoothly in toluene (85 °C) with only 1 mol % of catalyst loading (Scheme 1a). Contrarily

• PH3AuNHCOOBn [35] were ruled out by experimental and computational observations. Differently, addition of the nucleophile to the gold activated double bond took place with Markovnikov regioselectivity affording the intermediate 11. At this point many possible reaction pathways were evaluated to shed light on

• of alkenes catalyzed by Ph3PAuOTf (toluene, 85 °C, Scheme 8) [40]. In particular, primary and secondary sulfonamides reacted smoothly with mono and disubstituted alkenes delivering nitrogen compounds 22 and 23 with Markovnikov regioselectivity (Scheme 8a). Moreover, N-protected pyrrolidines 24 and 25

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• triethylsilane and BF3·Et2O [53], affording 11. Oxidative cleavage of 11 with KMnO4/Bu4NBr [54] afforded iso-C12 acid 1. Alternatively, anti-Markovnikov hydration of 11, using I2/NaBH4 then hydrogen peroxide [55], afforded the alcohol 12, and oxidation of 12 with KMnO4/Bu4NBr afforded iso-C13 acid 2

Gold(I)-catalysed one-pot synthesis of chromans using allylic alcohols and phenols

• Eloi Coutant,
• Paul C. Young,
• Graeme Barker and
• Ai-Lan Lee

Beilstein J. Org. Chem. 2013, 9, 1797–1806, doi:10.3762/bjoc.9.209

• via an initial SN2 Friedel–Crafts regioselectivity, thus γ,γ-disubstitution on the alkene appears to be responsible for the switch in regioselectivity (Table 3, entry 11). This implies that the initial Friedel–Crafts allylation goes via Markovnikov selectivity. The unsubstituted secondary allylic

• or when the reaction is analysed before completion), the most likely mechanism is the expected gold(I)-catalysed Friedel–Crafts allylation of the phenol (via Markovnikov regioselectivity), with allylic alcohol [15][73], followed by cyclisation of the intermediate 9 via hydroalkoxylation to form

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• -alkylated amines in excellent yields (Scheme 21). Zeng and co-workers reported that cationic gold(I) complexes promote the addition of all types of non-tertiary amines 120 to a variety of allenes 121 to afford allylic amines 122 in good to excellent yields [58]. Importantly, the Markovnikov adduct was

• obtained in all cases. A similar Markovnikov hydroamination [59] could also be achieved via an intermolecular hydroamination of allenamides 123 with arylamines under mild AuPPh3OTf catalysis conditions to furnish allylamino (E)-enamides stereoselectively (Scheme 22). Hesp and co-workers have identified a

Alkene selenenylation: A comprehensive analysis of relative reactivities, stereochemistry and asymmetric induction, and their comparisons with sulfenylation

• Vadim A. Soloshonok and
• Donna J. Nelson

Beilstein J. Org. Chem. 2011, 7, 744–758, doi:10.3762/bjoc.7.85

• considered generally more efficient chiral auxiliaries compared with compound 1 [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. Reactions of benzeneselenenyl halides, including chiral compounds 1–3, with alkenes generally [55][56] exhibit high Markovnikov regioselectivity [57], with

• -chloroalkyl aryl sulfides and selenides, respectively. Conversely, differences between the two reactions have been reported, but the sources of these differences have not been fully explained: While arenesulfenyl chlorides add to alkenes with an anti-Markovnikov orientation, areneselenenyl chlorides add with

• Markovnikov orientation [34][55][57][63][69]. However, the orientation can be significantly influenced, or even reversed, by the steric bulk of substituents in the alkene [34][55], by changing the counterion [66][89], by aryl substituents on the C=C [19][60], or by added solvents such as methanol [27][64][89