A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• proteinogenic and nonproteinogenic α-amino acids were prepared. The synthetic methodology was based on nucleophilic addition of (trifluoromethyl)phosphinic acid or (difluoromethyl)phosphinic acid or its ethyl ester to substrates with C=N or activated C=C double bonds. Analogues of glycine, phenylglycine

• P–H compounds with CF3 or CHF2 groups attached to phosphorus. Three-component one pot Mannich-type reactions of CF3(H)P(O)(OH) with dibenzylamine and aldehydes were investigated. Also nucleophilic addition of CF3(H)P(O)(OH) or CHF2(H)P(O)(OEt) to Shiff bases, aminoacrylates and

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• ][2][3], because the ester group can serve as an activator to enhance the reactivity of the C=N double bond, thus making the following nucleophilic addition easier [4][5]. More attractively, the transformation of α-imino esters can provide an easy access to various natural and unnatural α-amino acid

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

• -dihydroisoquinolines 29, 35 and 36, respectively. The author suggested a mechanism that, starting from iminium intermediate 28, involves the nucleophilic addition on the electrophilic carbon atom of 28 and a protodemetalation yielding the desired 1,2-dihydroquinolines 29, 35 and 36. The annulation step giving rise to

• the presence of NHC catalyst, IPr) would attack the isoquinolinium-2-ylamide 43 to generate the new intermediate 46. Subsequently, methanol would be involved in the reaction via deprotonation and the nucleophilic addition to the carbonyl group to produce the desired 2-amino-1,2-dihydroisoquinoline 47

• by Jia and co-workers [99]. The authors got inspired by the recent development of the phosphine-catalyzed [3 + 2] cycloaddition of allenoates with electron-deficient species such as olefins and imines, which involves the in situ formation of a zwitterionic intermediate from the nucleophilic addition

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• derivatives are preferable. “Hydrolysis” of 6, and the KOR/dimsyl-K (11) system. Proposed carbenoid pathway from 6 to acid 10 and dimethyl sulfide (Me2S) in DMSO as the solvent. Proposed pathway to the main side-product 23 formed by nucleophilic addition of 11 to C-2 of 6. Possible course of the carbenoid

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• mechanism, as suggested by the experimental results, is not possible. In our model reaction 14a activates the nitroolefin in the nucleophilic addition step as shown in Figure 9, the tertiary amine functionality meanwhile serves as a base that deprotonates 2-hydroxy-1,4-naphtoquinone (17, Figure 9). The

One-pot synthesis of cyanohydrin derivatives from alkyl bromides via incorporation of two one-carbon components by consecutive radical/ionic reactions

• Shuhei Sumino,
• Akira Fusano,
• Hiroyuki Okai,
• Takahide Fukuyama and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2014, 10, 150–154, doi:10.3762/bjoc.10.12

• bromides and nucleophilic addition of a cyanide ion was investigated, which gave moderate to good yields of cyanohydrin derivatives in one-pot. Keywords: alkyl bromide; carbon monoxide; cyanohydrin; ethyl cyanoformate; multicomponent; radical reaction; Introduction Radical carbonylation reactions have

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• Mukaiyama–Isayama peroxysilylation of unsaturated compounds, the Kobayashi cyclization, the nucleophilic addition of hydrogen peroxide to carbonyl compounds, the ozonolysis, and reactions with the involvement of peroxycarbenium ions. Each part of the review deals with a particular class of the above

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• (17%, Table 1, entry 11). Mechanistic analysis Taking into account the structural variety observed in this family of reactions, a rational explanation is needed to understand the formation of such products. Here we describe a simplified hypothesis based on the well-known nucleophilic addition of

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• 1,3-dipolar intermediate A. In the meantime, the condensation of the aromatic aldehyde with 2-aminobenzothiazole affords an aldimine B. Secondly, the nucleophilic addition of 1,3-dipole intermediate A to aldimine B gives an addition intermediate C. Thirdly, the intramolecular nucleophilic attack of

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

• by nucleophilic substitution reactions using [18F]-fluoride ion (Scheme 7) [55][56][57][58][59][60][61][62][63][64][65][66][67]. For not only fluorination/fluoroalkylation, but also for defluorination, flow microreactor synthesis is quite effective. Defluorination involving a nucleophilic addition

• microreactor synthesis of photochromic diarylethenes was found to be effective; the generation of heteroaryllithiums and the subsequent nucleophilic addition/elimination with octafluorocyclopentene were successfully achieved (Scheme 12) [75]. As a significant progress, the selective synthesis of unsymmetrical

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• synthesis this reagent fulfils both functions at different stages: thus, the target 78 is achieved from N-(tert-butylsulfinyl)imine 75 through a nucleophilic addition/radical cyclisation sequence. The selectivity during the radical cyclisation (77→78) can be explained by the Beckwith–Houk transition-state

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

• and have to be used in large amounts. Thirdly, the formylation reaction was performed only in a 5 mmol scale and was not optimized for large scale synthesis. Asymmetric induction with Garner’s aldehyde Nucleophilic addition to Garner’s aldehyde gives an easy access to 2-amino-1,3-dihydroxypropyl

• ), viral infections, tumour metastasis, and neurodegenerative disorders. Through the addition of a nucleophile to the aldehyde (S)/(R)-1, a new C–C bond is formed, hence allowing carbon chain elongation and further functionalization. Nucleophilic addition of an alkyne to 1 gives access to propargylic

• nucleophilic addition of a lithiated alkynyl group to 1 in THF was selective, favouring the anti-adduct 14 (Scheme 8). Herold also noticed that the addition of hexamethylphosphorous triamide (HMPT) increased the selectivity from 8:1 (Garner) to >20:1 (anti/syn). HMPT co-ordinates to the Li-cation, thus

Gold(I)-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles

• Mathieu Morin,
• Patrick Levesque and
• Louis Barriault

Beilstein J. Org. Chem. 2013, 9, 2625–2628, doi:10.3762/bjoc.9.297

• benzothiophene 7 was isolated in 89% yield. The formation of this unforeseen product can be explained by the proposed mechanism illustrated in Scheme 2. The gold(I) complexation of alkyne 4 triggers the 5-exo-dig cyclization to produce intermediate 9. At this point, a nucleophilic addition of the thiophene unit

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

• years, tremendous developments were made, and some of the major contributes will be summarized in the present review. Mechanistically, it is generally accepted that the gold-catalyzed nucleophilic addition to alkenes proceeds through three elementary steps: i) activation of the C–C double bond by gold

• respect to different π-systems. In particular, the intrinsic inertness of alkylgold intermediate 1 (i.e. Csp3–Au bond) towards protodeauration (path a, Figure 2) determines the scarce reactivity of alkenes in nucleophilic addition reactions [6]. The use of allylic alcohols as C=C surrogates opens up an

• of inactivated alkenes relies on enantioselective processes, that still represent an unsolved issues in metal-free catalysis [87]. Elementary steps in the gold-catalyzed nucleophilic addition to olefins. Different approaches for the gold-catalyzed manipulation of inactivated alkenes. Computed

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• (Table 1, entry 1). This is probably due to the nucleophilic addition of methanol to the highly electrophilic trifluoroacetonitrile oxide. The utilization of the less nucleophilic alcohol hexafluoroisopropanol (HFIP) [33][34] led to the formation of a complex mixture (Table 1, entry 2). The oxidation of

Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

• Shinichiro Fuse,
• Nobutake Tanabe,
• Akio Tannna,
• Yohei Konishi and
• Takashi Takahashi

Beilstein J. Org. Chem. 2013, 9, 2336–2343, doi:10.3762/bjoc.9.268

• Table 1. We speculated that the slightly lower yield of 3c compared to 3b came from the instability of 3c during purification process. The compound 3c was less stable than 3b. Rojas et al. reported that the regioselectivity in the nucleophilic addition of an amidine to an imidochloride depends on the

• asymmetric ligand 3c was obtained, although similar reaction conditions were employed (Scheme 2). The result showed that the nucleophilic addition of amidine 10 occurred from the sterically more hindered nitrogen atom (path b). The structure of the asymmetric ligand 3c was unambiguously determined by 1H NMR

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• ) was carried out (Scheme 5). The aldehyde (R)-2, which was prepared from D-serine [42][43][44], underwent chelation-controlled nucleophilic addition of metallated alkyne 3 [45] to give the propargyl alcohol 14 in 84% yield and a syn-diastereoselectivity of >95:5 [7][46][47]. After tosylation of 14 (85

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones

• Marie Hoffmann,
• Solène Miaskiewicz,
• Jean-Marc Weibel,
• Patrick Pale and
• Aurélien Blanc

Beilstein J. Org. Chem. 2013, 9, 1774–1780, doi:10.3762/bjoc.9.206

• ]. Intermediate B, which could also be generated by carbophilic gold activation followed by nucleophilic addition of the acyloxy part, could evolve into the gold carbenoid species D [31]. Intermediate C, possessing the correct stereochemistry, and D might then cyclize by an attack of the carbonyl function on the

A simple, enaminone-based approach to some bicyclic pyridazinium tetrafluoroborates

• František Josefík,
• Markéta Svobodová,
• Valerio Bertolasi and
• Petr Šimůnek

Beilstein J. Org. Chem. 2013, 9, 1463–1471, doi:10.3762/bjoc.9.166

• yields without the need to isolate the intermediate 4. Pyridazinium salts 5 arise from azo-coupled enaminones 4 probably via the products of double azo coupling (Im) through an intramolecular nucleophilic addition followed by the loss of water. The statement is, however, based only on the structures of

Isolation and X-ray characterization of palladium–N complexes in the guanylation of aromatic amines. Mechanistic implications

• Abdessamad Grirrane,
• Hermenegildo Garcia and
• Eleuterio Álvarez

Beilstein J. Org. Chem. 2013, 9, 1455–1462, doi:10.3762/bjoc.9.165

• guanidines are commercially used as antifouling agents in marine paints and in the formulation of protective surface coatings [8][9][10]. N-Arylguanidines can be obtained by aniline insertion into the corresponding carbodiimide [11][12][13][14][15][16][17][18]. This nucleophilic addition can be efficiently

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• reactions such as nucleophilic substitution of P–X compounds with organometallic reagents, nucleophilic substitution of alkyl halides with phosphorus nucleophiles, and nucleophilic addition to polar unsaturated bonds. Recent advances in transition-metal catalysis have realized catalytic cross-coupling

Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

• Mostafa Kiamehr,
• Firouz Matloubi Moghaddam,
• Satenik Mkrtchyan,
• Volodymyr Semeniuchenko,
• Linda Supe,
• Alexander Villinger,
• Peter Langer and
• Viktor O. Iaroshenko

Beilstein J. Org. Chem. 2013, 9, 1119–1126, doi:10.3762/bjoc.9.124

• proceeds by regioselective attack of the central carbon atom of the 1,3-dicarbonyl unit to 4-position of the pyridinium salt and subsequent cyclization by base-assisted proton migration and nucleophilic addition of the oxygen atom to the 2-position, as was elucidated by DFT computations. Fairly extensive

• screening of bases and additives revealed that the presence of potassium cations is essential for formation of the product. Keywords: cyclization; density functional calculations; heterocycles; nucleophilic addition; pyridinium salt; Introduction The nucleophilic addition to pyridinium salts has recently

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• 3-hydroxypiperidine with para-methoxyaryliodide. Unexpectedly, the spectrum of the resulting amine 13b was not consistent with that of 13. Based on the general iodolactonization principle, the C–O dipole in an amide is aligned for a favorable nucleophilic addition due to the “double-bond character

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• intermediate A with isatinylidene derivative B to yield intermediate C. In the case of the reaction containing malononitrile, the nucleophilic addition of the amino group to the C–N triple bond in intermediate C resulted in spiro compound 1 with the tautomerization of the imino group to an amino group. In the

• case of the reaction containing ethyl cyanoacetate, the amino group could react with both the cyano group and the ester group in the adduct C. The nucleophilic addition of the amino group to the C–N triple bond finally afforded spiro[indoline-3,4’-pyridines] 2. On the other hand the amino group

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• , chiral nitroamines [55][56] are important intermediates directly transformed, via reduction of the nitro group, into diamines [57] or via a Nef reaction in amino acids [58]. Specifically, chiral 1,2-nitroamines have been mainly accessed by direct nucleophilic addition of nitronate anions to imine