Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• product of 1,2-addition of the C-nucleophile to the most reactive keto function and subsequent nucleophilic attack by the O-enolate on the conjugate C=C bond activated by two electron acceptors could become more preferable as compared to the alternative “normal” pathway, leading to adducts 10 and

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• regarding the facial selectivity, as the hydride was delivered to the convex face. An analogous reaction occurs when 2a is treated with AlMe3, affording the 1,2-addition product (Scheme 3) [59][60][61][62][63]. We next sought to establish the glyoxylate anion equivalency of the dithiane substructure in our

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• steps from commercially available furfuryl alcohol following a reported procedure (Scheme 1) [9]. Addition of the carbanion, generated in situ from dimethyl methylphosphonate and n-butyllithium in dry THF at −78 °C, to compound (+/−)-1 gave cyclopentenyl alcohol (+/−)-2 stereoselectively through a 1,2

• -addition mechanism. The stereochemistry of (+/−)-2 may be ascribed to a nucleophilic attack of the incoming nucleophile from the less-hindered face due to the presence of the silyl protective group. 1H and 13C NMR spectra were in accordance with the presence of a sole diastereoisomer. The reduction of

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• corresponding products 271 and 272 were isolated in 52–61% yields and their nOe analysis revealed the geometry of the alkene bonds to be E . A tandem 1,4–1,2 addition of dimethyl trimethylsilyl phosphite (DMPTMS, 273) to diazaheterocyclic compounds under microwave irradiation in acidic medium led to

• DMPTMS as a nucleophilic reagent on the N-protonated heterocycle followed by a 1,2-addition of DMPTMS on the N-silylated species lead to the diphosphorylated heterocycles after aqueous work-up. 8 Miscellaneous multicomponent reactions The reaction of pentanedial (284) with acetamide (283) and acetyl

• -(aminothioxomethyl)-1,2-dihydroisoquinolin-1-yl]phosphonates. Three-component stereoselective synthesis of 1,2-dihydroquinolin-2-ylphosphonates and 1,2-dihydroisoquinolin-1-ylphosphonates. Diphosphorylation of diazaheterocyclic compounds via a tandem 1,4–1,2 addition of dimethyl trimethylsilyl phosphite

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. Keywords: 1,2-addition; aryl iodides; ketones; nucleophilic addition; palladium catalysis; Introduction For our systematic studies on samarium diiodide promoted cyclizations

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• yields and enantioselectivity (Scheme 17). It is noteworthy that the catalytically generated Breslow intermediates undergo selective 1,2-addition with ynones and the competing Stetter-type reactivity was not observed [33]. Aza-benzoin reactions In aza-benzoin reactions, the acyl anions generated from

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• set up a 4π-electrocyclization, generating second intermediate 27. Elimination of the tertiary amine then gives γ-methylene cyclopentenone 28. 1,2-Addition reactions Henry reaction The use of cupreine and cupreidine derivatives in the addition of nitroalkanes to carbonyl compounds was first

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• solvent also affect the enantioselectivity, with iPr2N(n-Pr) and CH2Cl2 proving best. Notably, only 1,2-addition was observed. With respect to the alkyne, activated terminal acetylenes, such as ynones and propriolates, are best for this reaction. Unactivated alkynes give products in reasonable yields (63

Reaction of allene esters with Selectfluor/TMSX (X = I, Br, Cl) and Selectfluor/NH₄SCN: Competing oxidative/electrophilic dihalogenation and nucleophilic/conjugate addition

• A. Srinivas Reddy and
• Kenneth K. Laali

Beilstein J. Org. Chem. 2015, 11, 1641–1648, doi:10.3762/bjoc.11.180

• “X+” or “SCN+” at the central carbon of the allenyl moiety to form incipient allyl cations which on subsequent quenching with X− or SCN− furnished the 2,3-adducts as major products. The 1,2-addition products were only observed with TMSCl. The reactions were carried out in MeCN and in imidazolium

Design and synthesis of fused polycycles via Diels–Alder reaction and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha and
• Ongolu Ravikumar

Beilstein J. Org. Chem. 2015, 11, 1259–1264, doi:10.3762/bjoc.11.140

• with allylmagnesium bromide to produce 1,2-addition product 4. A molecular model of compound 3 reveals that its exo-face is more accessible for Grignard addition than the endo-face. Also, the X-ray structure of compound 5 indicates the stereostructure of 4. Further, the diol 4 was treated with four

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

• -unsaturated systems [13]. Most of the early work, including Michael’s, involved the use of stabilized or “soft” [14] nucleophiles such as malonates and nitroalkanes. Mechanistically, one can imagine a 1,2-addition of the nucleophile occurring versus the 1,4-addition if the EWG is a carbonyl compound, but this

• -addition of the carbonyl group is always a concern. In this case, the 1,2-addition product was not observed. The authors concluded that the 1,2-addition reaction did not occur because the magnesium salts that were present in the solution would be chelated strongly by the oxygen in the chiral auxiliary and

• the oxygen of the resulting enolate of the CA reaction. This chelation to the magnesium would retard the 1,2-addition reaction from occurring. Since the Mukaiyama publication, there have been many chiral auxiliaries studied in DCA reactions of α,β-unsaturated amides [35]. Figure 2 highlights a few of

A convenient enantioselective decarboxylative aldol reaction to access chiral α-hydroxy esters using β-keto acids

• Zhiqiang Duan,
• Jianlin Han,
• Ping Qian,
• Zirui Zhang,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 969–974, doi:10.3762/bjoc.10.95

• stereocontrolled nucleophilic alkylation [15][16][17][18][19], alkynylation [20][21], 1,2-addition [22][23][24][25][26] and aldol reaction [27][28][29][30][31][32] have been developed. Various nucleophiles such as organometallics, boronic acids and unsaturated ketones can be tolerated in this context (Figure 2

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

• corannulene (1) to afford predominantly the cyclopropanated product 9 [39], whereas methyllithium adds to 10, giving the 1,2-addition product 11, after alkylation of the resulting anion by methyl iodide [40]. In contrast to these examples, no planar PAH has ever been observed to suffer direct covalent bond

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• -coupling products into tandem reactions. The second goal could be achieved by classifying reactions on the basis of the involved reactants, the reaction type or the role of the catalyst. Review A3-coupling-type reactions Silver catalysis The catalytic direct 1,2-addition of alkynes to imines and iminium

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

• quaternary centers at the ring junction. We decided to start the sequence with known enone 15 [39] and intended to construct the all-carbon quaternary center at C13 by substrate controlled α-functionalization. The second quaternary center at C14 might be established by 1,2-addition and finally, ring-closing

• envisaged to be constructed by 1,2-addition, using the free β-hydroxy functionality in 63 as directing group. Several conditions with allyl boronates, stannanes, silanes, indium, magnesium bromide, cerium, zinc bromide and other reagents have been screened. Finally, the best result was achieved with

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• sequence, with concomitant reduction of the ester to give alcohol 200. Oxidation and Wittig olefination gave olefin 201. Lithium bromide exchange followed by 1,2-addition to ketone 202 yielded tricyclic 203, which was immediately subjected to acidic hydrolysis to give the desired tricyclic core skeleton

Synthesis of novel derivatives of 5-hydroxymethylcytosine and 5-formylcytosine as tools for epigenetics

• Anna Chentsova,
• Era Kapourani and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 7–11, doi:10.3762/bjoc.10.2

• the aldehyde group (1,2-addition) were not observed. The formation of compounds 8a–d can be explained assuming a Michael-type reaction of aldehyde 5 with organometallic reagents, subsequent isomerisation of the double bond followed by removal of one TCBoc group during the reaction and work-up as shown

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

• ]. Chisholm has been looking for milder catalytic metal-alkyne nucleophiles for carbonyl 1,2-addition reactions, which wouldn’t enolize the labile α-protons next to a carbonyl group (Scheme 17) [71]. They found that a Rh(I)-catalyst with a monodentate electron rich phosphine ligand 42 formed a nucleophilic

Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

• Satoshi Okusu,
• Yutaka Sugita,
• Etsuko Tokunaga and
• Norio Shibata

Beilstein J. Org. Chem. 2013, 9, 2189–2193, doi:10.3762/bjoc.9.257

• Michael addition reaction, even in a racemic, non-stereoselective fashion [1][2][3][4][5]. The nucleophilic trifluoromethylation to conjugated alkenes essentially occurs solely via a 1,2-addition [1][2][3][4][5][6][7][8][9][10][11], not a 1,4-addition (Scheme 1), with the exception of non-general examples

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• of N-1,4-addition and C-1,2-addition/β-elimination [16][17], effectively leading to a variety of nitrogen heterocyclic motifs, such as 3, which are prevalent among alkaloids (Scheme 1) [16][26][27][28][29][30][31][32]. However, there was a significant deficiency in this annulation: the inability to

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

• related bonds, their potential utility lies in the fact that they can also react with unpolarized H–H and C–H bonds (including those of methane). The result is a 1,2-addition of X–H across the M═E bond to give a M(X)(EH) species, which may in some cases react further. A prominent example was reported by

• the types of reactivity discussed thus far, there are several distinct routes to the functionalization of C–H (or E–H) bonds using metal–ligand multiply bonded FLPs. If C–H activation is effected by 1,2-addition across a M═E bond, then reductive elimination could result in a net C–H insertion of

• a transformation has not been realized with the early metal complexes that are most reactive toward C–H bonds, probably because reductive elimination is strongly disfavored relative to the 1,2-elimination of alkane. Another possibility would be an initial 1,2-addition of a C–H bond across M═E

Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

• Lukas Kupracz,
• Jan Hartwig,
• Jens Wegner,
• Sascha Ceylan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1441–1448, doi:10.3762/bjoc.7.168

• protocol starts from alkenes, which are transformed by a 1,2-addition of iodine azide and then to the corresponding vinyl azides. Furthermore, for the first time we present the copper-mediated Huisgen-type “click” cycloaddition of vinyl azides with alkynes to yield vinyl triazoles under inductive-heating

When gold can do what iodine cannot do: A critical comparison

• Sara Hummel and
• Stefan F. Kirsch

Beilstein J. Org. Chem. 2011, 7, 847–859, doi:10.3762/bjoc.7.97

• developed a 5-endo approach to the iodocarbocyclization between ß-keto esters and non-terminal alkynes (Scheme 13b) [108]. Initially, 1,2-addition of iodine to alkynes such as 45 proved problematic, which was resolved by decreasing the molarity of the iodine in CH2Cl2 from 0.3 M to 0.05 M. This favored the

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• dependent on the electronic properties of the two reaction partners [14]. He reported that 1,2-addition usually prevails when a high degree of charge transfer is involved in the exciplex (ΔGET below 0.5 eV). A substituent at position 1 stabilizes the charge which develops on the aromatic ring, and therefore

A stable enol from a 6-substituted benzanthrone and its unexpected behaviour under acidic conditions

• Marc Debeaux,
• Kai Brandhorst,
• Peter G. Jones,
• Henning Hopf,
• Jörg Grunenberg,
• Wolfgang Kowalsky and
• Hans-Hermann Johannes

Beilstein J. Org. Chem. 2009, 5, No. 31, doi:10.3762/bjoc.5.31

• observed, a compound type which is produced (derivative 6) when benzanthrone was treated with phenyl lithium [3]. The yield of 4 was not improved by addition of a copper(I) salt in catalytic amounts [4]. This procedure should have favoured the ratio of a 1,4- to a 1,2-addition product [5]. The enol 4 is