Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• elimination reaction could then operate to give 22, either during aqueous work-up, or in situ collapse of the intermediate complex and subsequent reduction of the resulting iminium ion via elimination. As a Lewis acidic reducing agent, it was anticipated that DIBAL could be better suited to the reduction of

• in the benzylic position of the quinolin-2-one (20a/23b). Given the high temperature, it may be that 1,3-diaxial steric interactions between the benzylic substituent(s) and the intermediary iminium ion are such that a conformation needs to be adopted that both allows and indeed, favours the proposed

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

• Lewis acid (LA) catalysis strategy (Scheme 1, reaction 2) [49][50][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76]. The iminium catalysis plays an important dual role in the process. The formed iminium ion 4 derived from aldehyde 1 and an amine catalyst activates the C=C

• bond and sterically blocks the attack of the C=N iminium ion functionality posed by the bulky amine catalyst. In parallel, a LA promotes to open the D–A cyclopropanes 2. The cooperative activation of two independent substrates by respective iminium and Lewis acid catalysis may enable an unprecedented

• not shown). The absolute configuration of cyclopentanes 3’ and 3’’ were determined based on the derivatives 7h’ and 7h’’ of 3h (Scheme 2) [95]. We proposed two possible transition states (TS) 8a’ and 8a” to rationalize the observed configurations (Scheme 3). The trans-C=C double bond in iminium ion 4

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

• , improved both the yield and enantioselectivity of the transformation by facilitating the formation of the iminium ion intermediates. A variety of vinyl ketones 118 were explored for the reaction, and when R4 was benzylic, shorter reaction times could be employed (41–48 h) and higher yields and

(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

• designed and developed, the functionalization of carbonyl compounds via enamine and iminium ion intermediates are the most common [4][5] (Scheme 1). The carbonyl compound condenses with the amino catalyst, to form an iminium ion, subsequent deprotonation leads to the highly nucleophilic enamine. This kind

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

• -branched enones 47 via iminium ion catalysis (Scheme 12) [47]. This study found that the catalytic function could be modulated to induce diastereodivergent pathways by applying an external chemical stimulus (Scheme 12). Several conclusions were made from this study, one of which was that the hydrogen

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

• -based catalysts [9][10][11][12][13][14][15]. Among these, chiral copper catalysts have been used with remarkable success in the alkynylation of cyclic iminium ion and oxocarbenium ion intermediates. This review will focus on the development of these enantioselective, copper-catalyzed alkynylations

• terminal alkyne to the enamine simultaneously generates the copper acetylide and iminium ion, which are proposed to both bind to the chiral copper catalyst (see 4). A broad scope in the acetylene was observed, with arylalkynes resulting in the highest ee’s. To our knowledge, these were the first

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• -carbenoid in the C3-position of N-methylindole followed by elimination of bromide. The conjugated iminium ion is a very good electrophile and can undergo an electrophilic aromatic substitution in the C3-position of N-methylindole to form the bisindole product. Conclusion We have developed a mild and

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• % required for the supported imidazolidin-4-ones. Moreover, 4b was shown to be well-tolerated in a range of α,β-unsaturated aldehydes. The improved efficiency shown by 4b might derive from an anchimeric assistance in the hydrolysis step of the iminium ion. Interestingly, the presence of such an effect might

Hydrogenation of unactivated enamines to tertiary amines: rhodium complexes of fluorinated phosphines give marked improvements in catalytic activity

• Sergey Tin,
• Tamara Fanjul and
• Matthew L. Clarke

Beilstein J. Org. Chem. 2015, 11, 622–627, doi:10.3762/bjoc.11.70

• out as reductive amination or reduction of enamines need stoichiometric acetic acid to promote the formation of the iminium ion that is the substrate reduced in hydride reductions, which might not be compatible with other functional groups. To the best of our knowledge, the hydrogenation of

Eosin Y-catalyzed visible-light-mediated aerobic oxidative cyclization of N,N-dimethylanilines with maleimides

• Zhongwei Liang,
• Song Xu,
• Wenyan Tian and
• Ronghua Zhang

Beilstein J. Org. Chem. 2015, 11, 425–430, doi:10.3762/bjoc.11.48

• transformation [28][29][30][31][32][33][34][35][36][37][38]. Tertiary amine A generally generates a nucleophilic α-aminoalkyl radical B or an electrophilic iminium ion C via visible-light photoredox catalysis. Unfortunately the research of the α-aminoalkyl radical is limited in photochemical synthesis because it

• tends to form the iminium ion by one electron oxidation (Scheme 1) [39][40][41]. In the context of this research background, we investigated the α-aminoalkyl radical route to achieve the aerobic oxidative cyclization of N,N-dimethylanilines with maleimides to form the corresponding tetrahydroquinoline

A simple and efficient method for the preparation of 5-hydroxy-3-acyltetramic acids

• Johanna Trenner and
• Evgeny V. Prusov

Beilstein J. Org. Chem. 2015, 11, 323–327, doi:10.3762/bjoc.11.37

• attempts to remove the benzyl group under various catalytic hydrogenation conditions failed entirely. Cleavage of the DMB group with TFA [16] was also tried, but brought no success and extensive formation of polymerization products of the corresponding iminium ion was observed. Oxidative cleavage of the

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• ]-hydride shift with participation of the benzylic hydrogen to result in the zwitterionic iminium ion intermediates A. The 6-endo cyclization of this intermediate gave rac-trans-7a,b with high diastereoselectivity, which was governed by the C-2 chirality center of intermediate A. In contrast to the domino

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

• (+)-vincadifformine (Scheme 14) [106]. The key step in the synthesis was an iminium ion cascade reaction that formed the fused ring systems by coupling 3,3-disubstituted tetrahydropyridine 57 with indole derivative 58. The former coupling partner was derived from chiral α-quaternary lactam 60, which was constructed

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• enamine structure II. On the other hand, the comparison with the fragmentation of the structurally related ion [II*b]+ (Figure 5b) is instructive. It doubtlessly possesses an enamine structure since it can neither form a zwitterionic iminium ion nor undergo lactonization to oxazolidinone II’’b because of

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• 7) resulted in a decrease of the dr. This may be caused by a minor stereofacial differentiation of the intermediate carboxylate iminium ion during the nucleophilic addition of the isocyanide. Isocyanide 2b (Table 2, entry 3 and entry 4), formally derived from glycine, afforded satisfactory results

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

• the tertiary amine enables proton transfer from phosphorus to carbon (Table 5). The organocatalyzed hydrophosphination of α,β-unsaturated aldehydes has been described by Carlone et al. [133] and Ibrahem et al. [134]. The method is based on activation of the aldehyde 59 via iminium-ion formation by

Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes

• Theresa H. Nguyen,
• Soumitra Maity and
• Nan Zheng

Beilstein J. Org. Chem. 2014, 10, 975–980, doi:10.3762/bjoc.10.96

• cyclopropyl ring opening to generate distonic radical cation 26. The primary carbon radical of 26 adds to the terminal carbon of alkyne 27 to afford vinyl radical 28. Intramolecular addition of the vinyl radical to the iminium ion of distonic radical cation 28 closes the five membered ring and furnishes amine

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• the outcome of the sequence. The latter hypothesis of the iminium-ion stabilization obviously influences the lifetime of the zwitterion 13. Furthermore the enamine formed by deprotonation of 9 is a S,N-ketene acetal, which is significantly more nucleophilic than Fischer’s base (7). The higher

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 avoided the annoying aldehyde trimerization usually observed when reacting aliphatic aldehydes under the more investigated Cu(I) and Au(I) catalysis (see below). The proposed mechanism involved the formation of a silver acetylide, which is able to react with the iminium ion generated in situ from

• alkyne π-complex I with the acidification of the acetylenic hydrogen atom. Deprotonation by the imine produces the electrophilic iminium ion with simultaneous production of the Au(I)-acetylide II. An addition reaction produces propargylamine III and regenerates the gold cation. Amine III is trapped with

• between acyl chloride and imine, to give the propargylamide III. The proton released during the formation of the acetylide I activates the triple bond of propargylamide III which undergoes the attack from the amide oxygen atom. The benzyl group of the resultant iminium ion IV is lost as benzyl chloride by

Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones involving alkynes, aldehydes and thiourea/urea

• Jie-Ping Wan,
• Yunfang Lin,
• Kaikai Hu and
• Yunyun Liu

Beilstein J. Org. Chem. 2014, 10, 287–292, doi:10.3762/bjoc.10.25

• of iminium ion 8. Finally, an intramolecular cyclization of 8 leads to the formation of 9 which subsequently undergoes deaminative elimination to result product 5 by releasing the amine catalyst for further recycling (Scheme 3). Conclusion In conclusion, we have established an unprecedented amine

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

• iminium ion type DVCPR rearrangement (313 to 314, see Scheme 38), or a cyclopropylcarbaldehyde can be condensed with an amine to an imine, which then undergoes the DVCPR rearrangement (315 to 316, see Scheme 38). Müller and coworkers [227][228] investigated the trans-vinylisocyanato–cyclopropyl

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• as would be predicted for a reaction with the Bose–Evans ketene formed from benzyloxyacetyl chloride [30]. The low yield of β-lactam product is better understood when the reactivity of the intermediate pentafluorosulfanylated imine and the subsequently formed iminium ion are considered. The SF5 group

• increases the acidity of the α-proton of the imine 5 and of the iminium ion intermediate B formed on the initial nucleophilic attack of the imine on the ketene as illustrated in Scheme 4. The ring closure step requires bond formation between the iminium ion carbon and the enolate carbon B to be particularly

• group as shown in A. Cornforth control of the ring closure step of the zwitterion (B in Scheme 4) where the SF5 would be antiperiplanar to the iminium ion would lead to the observed diastereoselectivity (Scheme 1). This finding is consistent with dipolar effects being most important in reactions with

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• –Spengler reaction of dopamine (99) with 4-hydroxyphenylacetaldehyde (100), both derived from L-tyrosine (98) (Scheme 11). After oxidation and O-methylation, which is carried out by S-adenosylmethionine (SAM), (S)-reticuline (101) is obtained. Oxidation of the N-methyl group to the iminium ion and

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• of (−)-epimyrtine have been described to date including the intramolecular allylsilane N-acyliminium ion cyclization [6], the organocatalytic aza-Michael reaction [7], the intramolecular Mannich reaction [8], and the iminium ion cascade reaction [9][10]. More efficient, convenient and highly

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

• are emerging as a powerful tool in amine synthesis. This article reviews synthetic applications of amine radical cations produced by visible light photocatalysis. Keywords: α-amino radical; amine radical cation; catalysis; distonic ion; free radical; iminium ion; photoredox; visible light

• /or irreversible downstream reactions of 2. The second mode involves hydrogen atom abstraction from 2 to produce iminium ion 4, when a good hydrogen atom acceptor is present in the reaction. The use of amine radical cation 2 as the source of a hydrogen radical has been applied to a number of visible

• converted to iminium ion 4 by another one-electron oxidation. The acidifying effect of one-electron oxidation on the α-C–H bond remains debatable [56][57][58][59][60]. The rate for deprotonation of amine radical cation 2 has been measured experimentally by several groups, and a broad range has been obtained