Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• jaspine B (1) as an attractive target [29][30][31][32][33]. Our approach to 1 is based on the addition of a lithiated alkoxyallene with a chiral auxiliary to pentadecanal as electrophile. This step will generate the first stereogenic center and install the C14-alkyl chain at the later C-2 position of the

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• required such as Ruppert–Prakash reagent (TMSCF3) or TESCF3 to generate a CF3-nucleophile, and S-(trifluoromethyl)thiophenium salts or Togni’s reagent to generate a CF3+-electrophile, an alternative approach has recently been reported, by different groups, where highly reactive CF3 radicals are generated

• can be obtained via reaction of trifluoromethylthiolate with an electrophile like aryl halides. On the other hand, they can also be obtained by reacting aryl sulfides or disulfides under nucleophilic or radical conditions with a trifluoromethylation reagent [16][55][124]. Very recently, several

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• various robust routes (Scheme 31) [84][85]. Most of these transformations use condensation reactions between urea (3.6) and a bis-electrophile to generate the desired structures. For instance, ester 3.7 furnishes uracil (3.5), which in turn can be converted into cytosine (3.4) by selective amination with

• ammonia/ammonium chloride (Scheme 31). Alternatively, thymine (3.3) may be accessed by reacting methyl formylpropionate (3.8) which acts as a bis-electrophile with urea. Following construction of the pyrimidone core the linkage to the anomeric position of a ribose is best achieved using the Vorbrüggen

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• [61][62]. α-Amino radical 3 is strongly reducing [45][63], thus making the second one-electron oxidation facile. The last mode involves cleavage of a C–C bond α to the nitrogen atom, yielding a neutral free radical 6 and iminium ion 5. Iminium ion 4, an excellent electrophile, is amenable to

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• -defficient character of this heterocycle. An electrophilic aromatic substitution at the C-5 of a pyrimidine is usually difficult [1][3][4][5]. However, the presence of two or three activating groups leads to the successful introduction of an electrophile (Scheme 1) [1][6][7][8]. On the other hand

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• the molecules is important and that a combination of electrophilic radicals with preferably nucleophilic arenes results in the highest rate constants. This is opposite to the Minisci reaction where the radical acts as nucleophile and the arene as electrophile. The substitution at the N-atom of the

• . In order to ensure comparability the examples were chosen with phenyl substitution at N. They are shown in Scheme 5 and the results are summarized in Table 4. The notion that the radical acts as an electrophile and the arene as nucleophile is further corroborated by the highest rate constant for the

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• the electrophile 4. However, all of these reactions failed to provide satisfactory results and only lead to the recovery or the substantial decomposition of the starting material. We then turned our attention to the organocatalytic conjugated addition reaction. Among the various documented conditions

A Lewis acid-promoted Pinner reaction

• Dominik Pfaff,
• Gregor Nemecek and
• Joachim Podlech

Beilstein J. Org. Chem. 2013, 9, 1572–1577, doi:10.3762/bjoc.9.179

• electrophile (Scheme 5). Reaction of silyl ether and nitrilium cation leads to a cationic N,O-bis(trimethylsilyl)imino ester, which is hydrolyzed to a carboxylic ester. Formation of the Brønsted acid trifluoromethanesulfonic acid is to be expected under these reaction conditions, but seems to have no influence

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• epoxide electrophile. To this end, 41 was treated with tert-butyllithium at –78 °C in a 90:10 THF/HMPA mixture, referred to as the method of first choice for lithiation of complex dithianes (Scheme 11). Following warming to –42 °C, the reaction was quenched with deuterated methanol. Analysis of the

• decyanation step. We planned to synthesize 5 by reaction of the cyanohydrin acetonide 67 with the epoxide electrophile 66 (Figure 8) [67]. The dimethyl derivative of L-malic acid was chemoselectively reduced with borane-dimethylsulfide and sodium borohydride to afford diol 69 (Scheme 18) [68]. The primary

• acetonide diastereomer. In the course of investigating why 66 and 67 failed to react, attempts were made to trap the anion of 67 with a more reactive electrophile. Allyl bromide reacted rapidly, affording the product 73 as a single diastereomer (Scheme 19). The configuration of this compound, as well as

Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst

• Cybille Rossy,
• Eric Fouquet and
• François-Xavier Felpin

Beilstein J. Org. Chem. 2013, 9, 1426–1431, doi:10.3762/bjoc.9.160

• acceptable yields. The Sonogashira alkynylation–cyclization sequence was successfully applied to a variety of alkynes and iodo-anilines (Scheme 5). As a general comment, aromatic alkynes consistently furnished a high yield of the corresponding indoles whatever the nature of the electrophile (compounds 4, 21

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• cycloaddition, ylide formation, cyclopropanation and C–H insertion reactions [1][2][3]. A generally useful modification of diazo compounds is the substitution of the α-hydrogen for an electrophile. This substitution can be effected in the presence of a base or starting from the metalated diazo compound, and

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• with concomitant generation of another oxonium species 47. Intramolecular capture of this electrophile by the pendant hydroxy substituent then delivers the spirocyclic adduct 48. Alternatively, reaction of the tertiary alcohol of 42 with the oxonium cation 43 affords the ketal 44. Protonation of the

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• triggered by exposure of trimesylate 2 or a related electrophile to ammonia. A sequential alkylation process would serve as a viable alternative in the event of problems with this approach. In turn, cis-fused trimesylate 2 could be derived from trans-fused tricyclic ketone 3 by epimerization and standard

Ring-opening reaction of 2,5-dioctyldithieno[2,3-b:3',2'-d]thiophene in the presence of aryllithium reagents

• Hao Zhong,
• Jianwu Shi,
• Jianxun Kang,
• Shaomin Wang,
• Xinming Liu and
• Hua Wang

Beilstein J. Org. Chem. 2013, 9, 767–774, doi:10.3762/bjoc.9.87

• the synthesis of a series of symmetric substituted dithieno[2,3-b:3',2'-d]thiophenes and their ring-opening reactions in the presence of n-BuLi. The 3,3'-bithiophene-2-carbaldehydes were generated after quenching with an electrophile, i.e., dry DMF (Scheme 1) [5]. The uncommon ring opening of fused

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• vinylations have been recently reported on activated olefins [14][15]. Some years ago, we showed that the in situ generation of Ni(0) complexes in the presence of both the aromatic halide and the electrophile [16] represents an interesting alternative to electrochemical processes. The main advantages of the

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• subsequent alkylation and thioesterification steps. Alkylation was achieved on a millimole-scale by using D3-iodomethane with LDA as base. After optimization, the isolated yield of 2 was 37%. However, when CH3I was used as electrophile for comparison, the yield reached 54% plus the additionally formed

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• ) and in THF since a competing rearrangement is not a problem. Despite the carbolithiation now requiring an anion to act as an electrophile, the corresponding carbolithiated and protonated product 6a was obtained as a single diastereoisomer in excellent yield without chromatography (Table 3, entry 1

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione

• Nargis Sultana and
• Walter M. F. Fabian

Beilstein J. Org. Chem. 2013, 9, 594–601, doi:10.3762/bjoc.9.64

• rearrangements of biacetyl and benzil [11]. Car–Parrinello molecular dynamics simulations of the hydrolysis of formamide in basic solution indicated that the traditional view of attack by hydroxide anion rather than a first-solvation-shell water molecule is more likely; however, the more powerful electrophile

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• ), but for groups that are known to be sluggish in carbocupration reaction, such as the introduction of a Me group (Table 1, entry 2), yield is significantly lower. The presence of the vinylcopper was proved by the reaction with allyl bromide as a classical electrophile used in organocopper chemistry to

A new intermediate in the Prins reaction

• Shinichi Yamabe,
• Takeshi Fukuda and
• Shoko Yamazaki

Beilstein J. Org. Chem. 2013, 9, 476–485, doi:10.3762/bjoc.9.51

• addition to them, 13 H2O molecules are included as shown in Scheme 6. In the model, H2C=O catalyzed by H3O+ (a) works as an electrophile to add to the alkene. The addition follows Markownikoff's rule [39]. H2O (f) is the nucleophile to the left-hand carbon of the alkene. One proton of H2O (f) moves to H2O

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• towards organolithium addition and avoiding polymerization. Thus, the (−)-sparteine-mediated enantioselective intermolecular carbolithiation of (E)-N-benzyl-2-(prop-1-enyl)aniline (12) and subsequent trapping of the intermediate organolithium with a suitable electrophile, followed by an in situ ring

• closure and dehydration generates the substituted indoles 13 with high enantioselectivities (enantiomeric excess up to 86%) (Scheme 4). Different functional groups can be introduced at the C-2 position of the indoles by varying the electrophile [13][14]. The procedure has also been extended to the

• diastereomeric and enantiomeric ratios, in moderate yield. (Scheme 11) [42]. The resulting benzyllithium can also be trapped with electrophiles, though the stereoselectivity in this fourth center is not so high, and depends largely on the electrophile. However, in these examples, the chiral ligand induces the

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• of the bis-electrophile proved to be crucial to the outcome of the alkylation reaction (Scheme 4). The alkylation of 30 with either symmetric (1,2-dibromoethane) or asymmetric (1,2-dibromo-1-phenylethane) vicinal dihalides resulted in the efficient dimerization of 30 to afford the biprolyl

Alternaric acid: formal synthesis and related studies

• Michael C. Slade and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19

• analogue to an intermediate in a distinct formal synthetic route, and a third (unique) approach to the natural product alternaric acid. Highlighted in this study is the versatility of silyl glyoxylates to engage a variety of nucleophile and electrophile pairs to provide wide latitude in the approach to

• endeavors, both in natural-product synthesis and synthetic methodologies [20]. Key to their use in a variety of contexts is the ability of silyl glyoxylates to function as linchpin synthons for geminal coupling of nucleophile/electrophile pairs at a glycolic acid subunit (Scheme 1A), which allows the rapid

• approach, inherent in the use of aldehyde 3 as a coupling partner: inherently poor Felkin–Anh facial selectivity with respect to the aldehyde electrophile due to minor differentiation between the Et/Me groups [28][29][30]. In all cases, the facial selectivity was rather poor, i.e., approximately 1.7:1

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• allylation product of 4, whereas for the generation of 17 we have to assume that its precursor monoanion has the propargyl structure 16. In all these structures the lithium atom is only meant to mark the position of the carbon atom at which the electrophile attacks; no proposition about the nature of the

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• intermediate and the less-stable allyllithium 3, an intramolecular carbometallation may then occur to yield a chelation-stabilized vinyllithium 4 and drive the overall process to the formation of the heterocyclic ring system. Further reaction with an electrophile followed by aqueous workup or hydrolysis under

• corresponding pyridine 6a (81%) was obtained on a gram scale. With a chelation-stabilized vinyllithium being formed after the anionic 6-endo-dig cyclization, we next considered the possibility of trapping this vinyllithium with an electrophile, which might allow the introduction of an additional C-2 substituent