One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• involves a formal [4 + 1] cycloaddition of isocyanides [30] and imines, generated from the amidines and aldehydes, allowing straightforward access to diverse imidazo[1,2-x]azines [31][32][33]. In view of the significance of the GBB reaction and the imidazo[1,2-a]pyridine core structure, the further

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• the reaction with highly active dipolarophiles, such as electrophilic C=O [35], e.g., aldehydes [36][37][38], ketones [38][39], and imines [40], and nucleophilic enol ethers [38][41], enamides [42], and indoles [43]. Nonetheless, the reactions with the α,β-unsaturated aldehydes and ketones face

On the mechanism of imine elimination from Fischer tungsten carbene complexes

• Philipp Veit,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2016, 12, 1322–1333, doi:10.3762/bjoc.12.125

• chromium (by py or CO) for Cr(CO)5(E/Z-4) and Cr(CO)5(Z-6). Both pathways are compatible with the formation of the metal-containing products fac-[Cr(CO)3(py)3] and Cr(CO)6 by dissociation of the imines E-5 or E-7 or by dissociation of the carbenes E-4 or E-6, respectively (Scheme 1b,c) [42][44]. The

• -ylidene)(pentacarbonyl) W(CO)5(12) (Scheme 1f) [53]. In principle, the formation of imines from NH carbene complexes can occur by three conceivable fundamental pathways. The first pathway starts with the dissociation of the carbene followed by a 1,2-H shift at the free carbene (elimination–migration). The

• (pathway 1b, Scheme 3), respectively. In the latter case, Z-3 isomerizes to the thermodynamically preferred isomer E-3. The second pathway (carbene elimination–migration) starts with the elimination of the carbenes E-2 or Z-2 followed by an 1,2-H shift to give the imines E-3 (pathway 2a, Scheme 3) or Z-3

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• Synthesis of aminophosphonic acid derivatives 3, 4 and 5 Schiff bases 1a–h were prepared by refluxing pyrene-1-carboxaldehyde with an amine in methanol, hexane or dichloromethane for 24 hours and were used for further conversions as obtained. This harsh method to prepare imines had to be used, because the

• simple mixing of reagents in methanol at room temperature, which is the common mode d’emploi in such cases [5][7], did not provide satisfactory results. The reaction completion was monitored by 1H NMR and obtained imines 1a–h were isolated by simple evaporation of the solvent and were used for the

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• lower enantioselectivities for the addition of para-substituted anilines to α,β-unsaturated imines [41]. Gil and Collin have also reported on the same reaction as Sodeoka, but using a samarium-BINOL catalyst system, which proceeded with lower enantioselectivity [42]. Sodeoka found that minimizing the

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• imines, carbonyls or allene homologs. The resulting homologated nucleophile 8 may then be trapped in an intramolecular fashion by a π-allyl complex, which may concomitantly form from 6 through activation of the homoallylic functionality with a suitable transition metal catalyst. According to this concept

• already been reported in preliminary form [31]. Homoallylic amines of type 12 may be efficiently obtained through multicomponent reactions. These involve the nucleophilic allylation of imines which may be generated in situ by the condensation of an amine and a carbonyl compound. As shown in Scheme 2, two

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• of nitrogen-containing moieties, such as amides [86][87], N-heterocycles [88][89], imines [90][91], pyridine N-oxide [92], amines [93][94], as well as a variety of others [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• proline and its derivatives [31]. Recently, Hoveyda and co-workers designed a novel amino acid amide catalyst (cat. 4) for the asymmetric addition of unsaturated organoboranes to carbonyls and imines, producing the corresponding enantiomerically pure alcohols and amines in excellent yields [32]. As shown

A modular approach to neutral P,N-ligands: synthesis and coordination chemistry

• Vladislav Vasilenko,
• Torsten Roth,
• Clemens K. Blasius,
• Sebastian N. Intorp,
• Hubert Wadepohl and
• Lutz H. Gade

Beilstein J. Org. Chem. 2016, 12, 846–853, doi:10.3762/bjoc.12.83

• have a significant influence on the binding geometry und coordination properties of these bidentate P,N-donors. Keywords: P,N-ligands; phosphanylformamidines; phosphine imines; transition metal complexes; Introduction P,N-ligands have been applied in a wide variety of chemical reactions ranging from

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• or aminal (carbinolamine)-type compounds. Thus, we set out to investigate the reaction of 1 with amino acids. Simple imines could not be observed. Instead, compound 2 was obtained (Scheme 1), containing two camphor-derived moieties, bridged by a nitrogen atom, and its structure was fully elucidated

• of imines with certain carbonyl compounds is the basis for enzymatic transamination and many other reactions [20][21] while the Strecker degradation is one cornerstone in food chemistry [22]. We present here details on the characterization of compound 2, which extends the scope of Strecker

• Supporting Information File 3. From these calculations we can draw the following conclusions: i) imines formed by reaction of amino acids with carbonyl compounds have the tendency to lose CO2 upon deprotonation of the carboxyl group. Without a negative charge at the carboxyl group, decarboxylation is

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• , a wide scope of the N-Boc-protected imines 48, including aliphatic ones, reacted with an excess of the nitroalkanes 49 at low temperature. This afforded the corresponding products 51 with high yield, diastereomeric ratio and excellent enantioselectivity (Scheme 16) [55]. Some experimental results

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• also achieved organocatalytically with hydrogen bonding. Organocatalysts that contribute to hydrogen bond formation bear usually a urea or thiourea moiety and they mostly interact with carbonyl groups, nitro moieties or even imines that exist to the substrates, leading to increased electrophilicity

• cycloalkanones using catalyst 11 [18]. The enantioselective synthesis of indolo- and benzoquinolidine compounds through aza-Diels–Alder reaction of enones with cyclic imines [19]. Enantioselective [5 + 2] cycloaddition [20]. Asymmetric synthesis of oxazine derivatives 26 [21]. Asymmetric synthesis of bicyclo

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

• aldehydes react with an aza electrophile. Imines possessing an electron-withdrawing N-substituent constitute the most commonly used aza electrophile and the reaction affords an α-aminocarbonyl compound as the product. The NHC-mediated addition of aldehyde-derived acyl anions to nitroso compounds leading to

• ]. Meanwhile, the Breslow intermediate is produced from the aldehyde by the thiazolium 31-derived NHC. The union of these two reactive intermediates furnished α-amidoketones 32 in excellent yields (Scheme 18). A diastereoselective [4 + 1] annulation of phthalaldehyde with imines leading to the formation of cis

• framework [35]. The thiazolium precatalyst 31 can also efficiently mediate cross-aza-benzoin reactions of aromatic and heteroaromatic aldehydes with unactivated aromatic imines 34 (Scheme 20) [36]. A control reaction of the corresponding benzoin (instead of the aldehyde) and imine 34 also afforded the α

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

• ]. In this classic process, it was hypothesized that the 6’-OH group was critical in directing the incoming aldehyde electrophile (see Scheme 1 box). Soon after, Shi and co-worker demonstrated the use of β-ICPD in the reaction of imines 5 with methyl vinyl ketone (MVK, 6) using the same catalyst (Scheme

Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

• Huanzhen Ni,
• Weijun Yao and
• Yixin Lu

Beilstein J. Org. Chem. 2016, 12, 343–348, doi:10.3762/bjoc.12.37

• enantioselectivity of the reaction and was chosen for further investigations. With the optimized conditions established, the substrate scope of this [3 + 2] annulation was explored by varying α-substituted allenoates 1 and imines 2 (Table 2). Firstly, different ester groups at the allenoates were examined (Table 2

• , methoxycarbonylmethyl-substituted allenoate 1j also proved to be a suitable substrate (Table 2, entry 10). The scope of β,γ-unsaturated N-sulfonylimines was subsequently examined by employing a number of differently substituted imines (Table 2, entries 11–15). In general, all the reactions worked well and afforded the

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• , no report of valuable diastereocontrol by them has appeared so far. Successful examples of diastereoselective Ugi reactions have been reported only with chiral amines [15][16][17][18][19] or with chiral cyclic imines (Ugi–Joullié reaction) [20][21][22][23], although in the latter case, racemization

• -Boc imines 2 and catalytic L-proline [29][30], followed by reduction of 3 and cleavage of the Boc group. This short and straightforward synthesis allows the introduction of 2 diversity inputs (R1 and Ar), whereas stereochemical diversity can also be explored using D-proline or different, anti

• -selective organocatalysts. We prepared two known carbamoyl sulfones 1 [30][31] and transformed them without isolation of intermediates into a series of five Boc-protected β-aminoalcohols 4a–e (Scheme 2). Using caesium carbonate, carbamoyl sulfones were converted into the corresponding N-Boc-protected imines

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

• ; enantioselectivity; iminium ion; oxocarbenium ion; Introduction Nitrogen and oxygen heterocycles with α-stereogenic centers represent important classes of biologicially active compounds [1][2][3][4][5][6][7]. Enantioselective addition of chiral nucleophiles to imines, iminium ions, carbonyls, or oxocarbenium ions

• (oxazoline) (Box), and Quinap-type ligands (Figure 1). Review Additions to iminium ions Although this review will focus on enantioselective additions to cyclic electrophiles, it is worth noting that the first enantioselective additions of chiral copper acetylides to imines or iminium ions utilized acyclic

• enantioselective, metal-catalyzed additions of terminal alkynes to imines or iminium ions, and set the stage for subsequent development of enantioselective alkynylations of cyclic iminium ion substrates [21]. As discussed below, the catalyst systems identified in these reactions have largely informed those used

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• organozinc reagents to give amines [1]; iii) aldehydes to give amides [5][6][7]; iv) base to give imines [8]; v) alkyl and aryl C–H bonds in the presence of acid and visible light to form heterocycles [9][10]. Furthermore they have also been used for chlorination of aromatics in the presence of acid [11

• alkenes to make amines, aldehydes to make amides, and base to make imines is ongoing. Experimental All reagents were used as received from suppliers without purification. Sodium hypochlorite solution 10–15% available chlorine was purchased from Sigma-Aldrich. The accurate NaOCl concentration was

A concise and efficient synthesis of benzimidazo[1,2-c]quinazolines through CuI-catalyzed intramolecular N-arylations

• Xinlong Pang,
• Chao Chen,
• Ming Li and
• Chanjuan Xi

Beilstein J. Org. Chem. 2015, 11, 2365–2369, doi:10.3762/bjoc.11.258

• are not readily available and need harsh conditions. Herein we report a CuI-catalyzed concise and efficient method for the synthesis of benzimidazo[1,2-c]quinazoline derivatives through the intramolecular N-arylation reaction of bromo-substituted quinazolin-4(3H)-imines that are easily prepared from o

• (sp3) in 3a reacted through the Cu-catalyzed Ullmann reaction [18][19][20][21][22][23][24][25]. Inspired by the successful cyclization of quinazolin-4(3H)-imine 3a, further imines were prepared and subjected to the cyclization conditions. Notably, in this protocol, after work-up, the desired bromo

• -substituted quinazolin-4(3H)-imine derivatives 3 were directly employed in the next step reaction without the need for chromatographic purification and the results are summarized in Table 2. Quinazolin-4(3H)-imines 3 having methyl, fluoro or chloro substituents all worked well in the reaction and provided the

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• ][38], fragment couplings [39][40][41][42], and transition metal-catalyzed C–H bond functionalization of α,β-unsaturated imines and oximes [43][44][45][46][47][48][49][50]. We were inspired by the copper-catalyzed coupling of protected α,β-unsaturated oximes and alkenylboronic acids developed by

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• -dihydropyrroles also presumably form spiro-imines as primary products. However, the lactam carbonyl group facilitates the ring-opening of these cyclic imines by a new pathway of hydration and retro-Claisen-type reaction, providing rearranged 2-(2'-formamidoethyl)oxindoles. Keywords: ene-sulfonamide; imine

• radicals to make transient imines [1][2][3]. In turn, onward reactions of the imines provide assorted products including ketones and nitrogen heterocycles [4][5][6][7][8][9][10]. Figure 1a shows a generic addition/elimination reaction of ene-sulfonamides along with example transformations in Figure 1b from

• Renaud [8] and Zard [7] that probably involve imine intermediates. Recent work from our group considerably strengthened the case for α-sulfonamidoyl radical elimination reactions. We were able to isolate stable imines from treatment of an assortment of ene-sulfonamides bearing radical precursors [11

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• to imines (Scheme 2) [41][42]. The mechanism was believed to involve e– capture by the imine thereby forming α-aminodiphenylmethyl radicals that underwent hetero-coupling with the allyl radicals generated from the allylic C–H containing substrates. Cyclohexanes, dihydrofurans, cyclopentenes and α

• far accessed include adducts from alkenes and imines, a wide range of heterocycles from ring closures, radical homo-dimers and macrocycles as well as hydrogenated products from nitro-aromatics, alkenes and aldehydes. There is obvious scope for the discovery of additional donor and acceptor precursors

• phenanthrene [29]. SCPC assisted additions of allylic compounds to diazines and imines [40][41][42]. TiO2 promoted addition and addition–cyclization reactions of tert-amines with electron-deficient alkenes [43][44][45][46][47]. Reactions of amines promoted by Pt-TiO2 [48][49]. P25 Promoted alkylations of N

Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• -caprolactam from cyclohexanone oxime involving the BR. The activation energy for the BR is almost the same as that of the nucleophilic substitution at sp2 nitrogen. To synthesize various aza-arenes and cyclic imines, such as quinolines, aza-spiro compounds and dihydropyrroles, the intramolecular SN2-type

A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones

• Marcelo Isidoro P. Reis,
• Vinícius R. Campos,
• Jackson A. L. C. Resende,
• Fernando C. Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2015, 11, 1235–1240, doi:10.3762/bjoc.11.137

• ]+ of 395.1715. The structure of compound 23 was further elucidated by X-ray diffraction analysis (Figure 3). It confirmed the insertion of two imines to form a hexahydropyrimidine ring which is coupled to a 1,4-naphthoquinone moiety. Figure 3 shows the ORTEP diagram of compound 23 and the details of

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• unsaturated diester followed by a sequential aldol addition and lactonization reaction [13]. To address aforementioned challenges, we have recently reported the first example of a copper-catalyzed reductive aldolization–lactonization cascade reaction of α,β-unsaturated diesters with ketones [14] and imines