A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

• Anna Kuźnik,
• Roman Mazurkiewicz,
• Mirosława Grymel,
• Katarzyna Zielińska,
• Jakub Adamek,
• Ewa Chmielewska,
• Marta Bochno and
• Sonia Kubica

Beilstein J. Org. Chem. 2015, 11, 1418–1424, doi:10.3762/bjoc.11.153

• derivatives consist in the consecutive formation of two Cα–P bonds between a carbon electrophile (most often an electrophilic imine intermediate) and two identical molecules of the proper phosphorus nucleophile. Another group of methods requires the formation of a Cα–N bond between an easily accessible

• , symmetrical, nucleophilic methylenebisphosphonic acid derivative and a nitrogen electrophile. Both groups of methods result in symmetrical products with the same phosphonyl or dialkoxyphosphonyl groups [10][11][12][13][14][15][16][17][18]. Up until 1989, very little was known about the preparative feasibility

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• electrophile, it requires a strong Lewis base in order for CO2 to react [54]. Addition of CO2 to the activated epoxide then occurs with a very low activation barrier [55]. In contrast, it has been generally believed up to now that, in the catalysed reaction of CO2 and epoxides, both reactants need to be

Weakly nucleophilic potassium aryltrifluoroborates in palladium-catalyzed Suzuki–Miyaura reactions: relative reactivity of K[4-RC₆F₄BF₃] and the role of silver-assistance in acceleration of transmetallation

• Vadim V. Bardin,
• Anton Yu. Shabalin and
• Nicolay Yu. Adonin

Beilstein J. Org. Chem. 2015, 11, 608–616, doi:10.3762/bjoc.11.68

• 5% (19F NMR) (Scheme 3). It should be noted that 2,3,5,6-tetrafluoropyridine was not observed in the reaction mixtures in both cases. The use of the electron-rich C-electrophile, 4-IC6H4CH3 (9), instead of 3 leads to biphenyls 4-(4'-CH3C6H4)C6F4R (10c–f,h–p) in 60–80% preparative yields (see Table 2

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• intermediate. At this point, the carbanion can be either protonated to form the β-substituted product or an electrophile can be added to form the α,β-disubstituted product. The latter operation is often referred to as a three-component coupling due to the combination of the original unsaturated compound, the

• nucleophile, and the electrophile. In 1883, Komnenos reported the first conjugate addition where he added the diethyl malonate anion to ethylidene malonate [12]. This reaction was not fully investigated until 1887, when Michael thoroughly studied this reaction using various stabilized nucleophiles and α,β

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• -nucleophile and C6-imine electrophile in the proposed intermediates to cyclisation (see structure 27 in Scheme 7) is least for the gem-dimethyl compound 10 (3.042 Å) and larger for the monomethyl compound 9 (3.056 Å) and 7 (3.180 Å). With cinnamyl bromide, an additional variation in the product outcome was

• 31 (ball and stick representation). ORTEP data for 31 is given in Supporting Information File 1. Calculated values of ΔHf of the red diindolone substrate 10 and the bridged tetrahydrofuran product 22, plus the distance between nucleophile (O) and electrophile (C) in the proposed key reaction

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• employed for olefin polymerization [26][27]. Since compound 23 contains doubly activated methylene positions, it should be easy to alkylate or bis-alkylate it. Furthermore, use of a bis-electrophile such as 1,2-dibromoethane could lead to the [2.2]indenophane 26 or its isomer 27, both potential ligands for

Matsuda–Heck reaction with arenediazonium tosylates in water

• Ksenia V. Kutonova,
• Marina E. Trusova,
• Andrey V. Stankevich,
• Pavel S. Postnikov and
• Victor D. Filimonov

Beilstein J. Org. Chem. 2015, 11, 358–362, doi:10.3762/bjoc.11.41

• with the work of Matsuda’s group [2], who used a diazonium salt as a high-reactive electrophile for a Heck reaction, the Matsuda–Heck reaction does require the addition of neither bases nor ligands and is carried out under very mild conditions [3]. Furthermore, diazonium salts are more often prepared

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• as the second stage in a two-step cross-dehydrogenative C–O coupling. The formation of a new C–O bond generally takes place with the involvement of an O-nucleophile, an O-radical, or an O-electrophile. In the oxidative coupling with O-reagents as nucleophiles, electrophilic intermediates that are

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• halides as has been previously reported [42]. The authors describe generation of a bis-organozinc species which, upon addition to an electrophile, generates an intermediate which can undergo β-hydride delivery to a second electrophile. In this case addition to 5a generates an intermediate organozinc

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

• Radhey M. Singh,
• Kishor Chandra Bharadwaj and
• Dharmendra Kumar Tiwari

Beilstein J. Org. Chem. 2014, 10, 2975–2980, doi:10.3762/bjoc.10.315

• coupling of an activated alkene with an electrophile (usually aldehydes or imines) in the presence of a catalyst (Figure 1). The reaction is organocatalytic, atomically economical and operationally simple in nature. Most importantly, it results in the synthesis of densely functionalized molecules, also

• appending other functionalities/groups for intramolecular transformations. Other reports have used this feature for the development of an intramolecular MBH reaction: Corey et al. (total synthesis) [29], Pigge et al. (ruthenium complexes as an electrophile) [30], and Basavaiah et al. [31][32]. Isatin has

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• . Intermolecular cyclizations generally fall into two further categories. In the first scenario, an anodically generated nucleophile (cathodically generated electrophile) reacts with an electrophile (nucleophile) present in solution. Consequently, an intermediate is formed, which undergoes ring-closure reaction

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• the nine-membered ring led to tricyclic compound 45. The pyrrole ring of 45 was formed by intramolecular condensation of cinnamyl amide 46, which is prepared via union of quaternary piperidinone 47 and cinnamyl electrophile 48. We envisioned that our allylic alkylation of lactam enolates would furnish

Synthesis of 2-trifluoromethylpyrazolo[5,1-a]isoquinolines via silver triflate-catalyzed or electrophile-mediated one-pot tandem reaction

• Xiaoli Zhou,
• Meiling Liu,
• Puying Luo,
• Yingjun Lai,
• Tangtao Yang and
• Qiuping Ding

Beilstein J. Org. Chem. 2014, 10, 2286–2292, doi:10.3762/bjoc.10.238

• electrophile-mediated conditions is described. Various trifluoromethylated pyrazolo[5,1-a]isoquinolines were afforded in moderate to excellent yield by this developed method. Keywords: [3 + 2] cycloaddition; electrophile; N’-(2-alkynylbenzylidene)hydrazide; silver triflate; tandem; Introduction Isoquinolines

• cores [11][14] and the synthesis of novel fluorinated heterocycles [27] with potential biological applications, herein, we describe an efficient method for the one-pot synthesis of trifluoromethylated pyrazolo[5,1-a]isoquinoline derivates via a Lewis acid (AgOTf) or an electrophile- (I2 or ICl) promoted

• 1i reacted with 2, leading to the desired pyrazolo[5,1-a]isoquinoline 3i in 90% yield (Table 2, entry 9). Subsequently, based on our previous reports on electrophile-mediated electrophilic cyclization reaction [28][29], one-pot tandem electrophilic cyclization/[3 + 2] cycloaddition of N’-(2

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• salt [11]. This synthesis has been streamlined by cross dehydrogenative coupling (CDC) – a powerful method for C–C-bond formation via the C–H bonds of a pro-nucleophile and a pro-electrophile [12][13][14]. A landmark contribution published by Li and co-workers reported the successful introduction of

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• asymmetric [3 + 2] annulations. Through intramolecular hydrogen bonding, the bond-forming transition-state geometry between electrophile and the zwitterionic intermediate formed from the allenoate and the multifunctional chiral phosphine can be better organized, thereby delivering annulation products in high

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• to the electrophile compared to the conventionally accepted model [31]. The use of other electrophiles for the stereoselective formation of C–N bonds has also been reported. Thus, α-amino-α-alkyl phosphonic acids [32][33][34] could be obtained through amination and azidation of phosphonamide anions

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

• precursor such as 13a (Table 1) [49]. A nucleophilic phosphide reagent was prepared by deprotonation of 13a in the presence of (−)-sparteine. The subsequent alkylation of the lithium phosphide with an electrophile proceeded with good enantiocontrol via dynamic resolution. One enantiomer is thermodynamically

• exchange. After reaction of the phosphide anion 20 with an electrophile, the chiral tertiary phosphine boranes 12b are formed with retention of configuration at the phosphorus atom. Catalytic C(sp3)–P bond formation Only a few examples of a metal catalyzed C(sp3)–P cross-coupling exist and they are mostly

• diastereomeric metal–phosphido complex 34 is formed. Rapid pyramidal inversion of this key catalytic intermediate 34 occurs. This complex performs a nucleophilic attack on the electrophile resulting in tertiary phosphines 10, in which the substituent ‘E’ comes from the electrophile. If the inversion of the

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• selectivity. The molecule behaves as an electrophile toward the bromoenolate (deprotonated bromomalonate) in the Bingel–Hirsch reaction and as an electrophile toward the 1,3-dipole (azomethine ylide) in the Prato reaction. Consequently, the LUMO of circumtrindene is the frontier molecular orbital that should

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• isocyanide-based reactions is that the isocyanide functionality can act both as nucleophile and electrophile at the C1-carbon, which makes the construction of linear peptide-like structures possible [20]. Cyclic peptidomimetics can be obtained via subsequent transformations that in turn are possible via e.g

Zirconoarylation of alkynes through p-chloranil-promoted reductive elimination of arylzirconates

• Xiaoyu Yan,
• Chao Chen and
• Chanjuan Xi

Beilstein J. Org. Chem. 2014, 10, 528–534, doi:10.3762/bjoc.10.48

• yield (Table 1, entry 5). When allyl bromide was employed as electrophile in the presence of CuCl, the allyltriarylethylenes were formed in 43% to 45% yields (Table 1, entries 6 and 7). Cross coupling with iodobenzene in the presence of CuCl/Pd(PPh3)4 afforded tetraarylethylene in 31% yield (Table 1

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• – discovered and mechanistically elucidated by Oliver Flögel – features a three-component reaction that employs alkoxyallenes, nitriles and carboxylic acids: upon treatment with n-butyllithium the allene is lithiated in α-position to the alkoxy moiety; the addition of a nitrile as electrophile to this highly

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• the thermodynamic enolate of 2-methylcyclohexanone (5) and the bicyclic electrophile 12 (Scheme 2). A challenging synthetic problem appears to be the construction of the stereochemically dense trans-fused C–D ring system 12, which possesses four stereogenic centers including two contiguous asymmetric

Modulating NHC catalysis with fluorine

• Yannick P. Rey and
• Ryan Gilmour

Beilstein J. Org. Chem. 2013, 9, 2812–2820, doi:10.3762/bjoc.9.316

• independently. Initially, the bulky diphenylfluoromethyl-containing triazolium salt 5 was subjected to the optimised conditions. It was envisaged that one of the phenyl rings might assist in the facial discrimination of the activated electrophile, as a consequence of the fluorine gauche effect (ΦNCCF −54.0

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• reactions of RFLi avoiding the β-elimination [80]. In the case of benzaldehyde as an electrophile, the reactions could be conducted at 0 °C, although much lower temperatures such as −78 °C are required to avoid the decomposition of perfluoroalkyllithium intermediates in batch processes (Scheme 13). However

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• ]. We have recently reviewed the literature on the synthesis of 1,2-vicinal amino alcohols [53]. Use of Garner’s aldehyde for the synthesis of non-natural amino acids through ethynylglycine has been reviewed [54]. In the following section, significant findings in the use of 1 as an electrophile and