Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• [22]. Starting from the similar isonitrile structure, 6-aroylated phenanthridines via base promoted homolytic aromatic substitution (BHAS) can be prepared [23]. Several photoinduced synthetic procedures were also applied. For instance, the photochemical cyclization of N-benzylanilines was used for

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• Kingsbury reported a facile synthesis of N-methylated di- and tri-peptide polyoxins by the Ugi reaction (Scheme 16) [81]. The aldehyde 36, aq methylamine, racemic isonitrile 37, and (S)-N-(benzyloxycarbonyl)phenylalanine were combined in MeOH to produce 38 as a mixture of four possible diastereoisomers in a

• , isovaleraldehyde, and isonitrile-substituted nucleoside 51 in methanol yielded the desired product as a 1:1 mixture of diastereoisomers, which were fully deprotected using aq TFA to furnish the muraymycin analogue 52. This successful route to the MRYs was then applied in the total synthesis of muraymycin D2 and

•  22) [89]. The urea dipeptide 55, 2,4-dimethoxybenzylamine, the protected (S)-2-(methylamino)propanal, and isonitrile 56 were simply combined in ethanol at ambient temperature for 48 h. The expected compound 57 and its epimer were obtained in reasonable yields, and were separated by column

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

• , Italy Dipartimento di Chimica, Materiali e Ingegneria Chimica ‘Giulio Natta’, Politecnico di Milano, p.zza Leonardo da Vinci 32, 20133 Milano, Italy 10.3762/bjoc.10.141 Abstract An efficient Ugi three-component reaction of a preformed chiral ketimine derived from isatin with various isonitrile and acid

• upon adding MgBr2, even though this promoter was shown to perform well in other reactions on ketimine 1. Evidently, in this case, the effective protonation of the nitrogen would be required in order to efficiently carry out the attack of the moderately nucleophilic isonitrile. An increase of the

• amine and the isonitrile-derived primary carboxamide functional groups (Scheme 1). Also, this chemical correlation of the major diastereoisomer 10a allowed us to further confirm the prevailing S-configuration at the tetrasubstituted stereocenter C3 of the Ugi products. Compound 15a was submitted to a

The Ugi four-component reaction as a concise modular synthetic tool for photo-induced electron transfer donor-anthraquinone dyads

• Sarah Bay,
• Gamall Makhloufi,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 1006–1016, doi:10.3762/bjoc.10.100

• -only systems 10 were also prepared by Ugi 4CR from the amino derivatives 4 and acetaldehyde (9), in moderate to good yield, with acetic acid (6) and tert-butyl isocyanide (7) as the corresponding acid and isonitrile components (Scheme 2). The appearance of single signal sets in the 1H and 13C NMR

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

• , cyclizations can also be initiated by activation of the Ugi-product via an Ugi Activation–Cyclization procedure and involves the use of convertible isocyanides as Ugi-substrates. An example of a convertible isonitrile is Armstrong’s isocyanide which can be cleaved after acidic treatment (Scheme 5). A

• ]. However, in the last decade two other groups, independently, published Ugi-MCRs towards these cyclic dipeptide isosteres. Hulme et al. reported an Ugi-Deprotection–Cyclization strategy using resin-bound convertible isonitrile 67 to provide primary and secondary γ-lactams 70 in high purities over five

Multicomponent reactions II

• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 115–116, doi:10.3762/bjoc.10.7

• addition, a lot of syntheses of heterocycles from the early days are MCR, and these reaction sequences paved the way to a multitude of applications. Moreover, Ugi's groundbreaking developments in isonitrile-based chemistry and his conclusions demonstrated that MCR are not only highly practicable in the

• again presents a snap shot of this highly dynamic field. With the traditional formats of letters, full papers, and reviews it spans the broad range of modern chemistry, including organocatalytic, organometallic, transition metal-catalyzed, radical reactions, condensation and isonitrile-based MCR

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• the domino cyclization (Table 2, entries 4, 6, 11, 12, 14, 15). Substituents like tert-butyl, cyclohexyl and n-butyl on the isonitrile are well-tolerated for the domino cyclization on the second position of the indole (Table 2, entries 1–16). Regarding the substituents coming from the acid part, tert

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• isonitrile 4 as the key transformation was envisioned to yield racemic viridic acid (±)-1 (Scheme 1b) [12]. Besides furnishing the desired natural product in only four steps, the MCR approach allows a ready access to analogues endowed with a proteolysis-resistant peptoid moiety [13]. Recently, we

• with (±)-1 can give an estimation of the relevance or effect of the configuration of the asymmetric center on the biological activity. With this goal in mind, the Ugi-4CR between methylamine, isobutyraldehyde, dipeptide 3, and the anthranilate-derived isonitrile 4a was planned (Scheme 1) [21]. For the

• ammonia or an ammonia equivalent, such as 2,4-dimethoxybenzylamine (DMB-NH2), as amino component, formaldehyde as oxo-component, and a convertible isonitrile [22][23][24][25]. Although many convertible isonitriles are reported in the literature [24][26], the recently developed 4-isocyanopermethylbutane

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• preliminary communication in 2009 [22]. As shown in Figure 2a, we conceived the modular assembly of three building blocks onto the piperidine-based manifold 6 with a carboxylic acid group. Ugi condensation [23][24][25] of 6 with indole-3-carbaldehyde 7, isonitrile and amine building blocks 8 and 9, followed

• of 15, isonitrile 21, indole-3-carboxylic acid derivative 58 and aldehyde 59 produced a 1:1 diastereomeric mixture of the dipeptidyl intermediate. Stepwise installation of the α-diazocarbonyl group produced 62 in good yield. The cyclization precursor 62 has a different arrangement of the branched

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• the reactivity of the 2-lithio-oxazoles resulting from the ready deprotonation, with n-BuLi at low temperature, of the most acidic C2-proton (pKa = 20–22 was suggested), which is complicated by the coexistence of a ring-open isonitrile tautomer. In particular, the treatment by trimethylstannylchloride

• direct arylation of oxazole was further improved for scale-up (Scheme 2) [34]. The C2-magnesation of oxazole was first performed with lithium tributylmagnesate at room temperature, and rapid evolution of the C2-magnesated oxazole to a ring-open isonitrile tautomer was evidenced by 1H NMR spectroscopy

• by the isonitrile function, leading to the ring-close aryloxazol-2-yl palladium complex delivering products after a final reductive elimination step (Scheme 3). Catalytic direct (hetero)arylation of (benz)oxazoles Palladium- and/or copper-catalyzed direct (hetero)arylation with halides: Synthetic

Synthesis of (−)-julocrotine and a diversity oriented Ugi-approach to analogues and probes

• Ricardo A. W. Neves Filho,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2011, 7, 1504–1507, doi:10.3762/bjoc.7.175

• intermediate 5 was converted to the respective imine as depicted in Scheme 2 and then reacted with (S)-2-methylbutanoic acid and isonitrile 7 to afford the intermediate 8 in 61% yield. This compound was then hydrogenated to afford 9 and then directly coupled with 1-pyrenemethylamine, by using EDCl as coupling

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

• Ameer F. Zahoor,
• Sarah Thies and
• Uli Kazmaier

Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151

• isonitrile-based MCRs (IMCR) especially have developed exceptionally well during the last few decades [7][8]. Based on the pioneering work of Passerini, who observed the first three-component coupling of carbonyls with carboxylic acids and isonitriles in 1921 [9], the so-called Passerini reaction became a

Multicomponent reactions

• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 960–961, doi:10.3762/bjoc.7.107

• lead structures of active agents, catalysts and even novel molecule-based materials. This Thematic Series on multicomponent reactions represents a snapshot of a highly dynamic field and spans a broad range, from recent advances in isonitrile-based MCR to transition metal catalysis in MCR; from peptidic

Complete transfer of chirality in an intramolecular, thermal [2 + 2] cycloaddition of allene-ynes to form non-racemic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2011, 7, 601–605, doi:10.3762/bjoc.7.70

• spirooxindole-containing skeletons 2 in a two-step one-pot process from propargyl acetates 1 [4] (Scheme 1). Inspired by this rapid entry into the molecularly complex substructure 2, and the structural similarity to welwitindolinone A isonitrile (3), we became interested in the synthesis of chiral non-racemic

• allene-yne that generates a chiral non-racemic spirooxindole from a chiral non-racemic allene. Furthermore, this reaction could also be applicable in the enantioselective synthesis of natural products that contain a spirooxindole core, such as welwitindolinone A isonitrile. We are currently working to

• . Conversion of propargyl acetate 1 to spirooxindole 2 containing the core framework of welwitindolinone A isonitrile (3). Preparation of enantiopure propargyl acetate 7 (R = Ac). Microwave irradiation of allenyloxindole 8. Screening conditions for the formation of allenyloxindole 8. Supporting Information

A thermally-induced, tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition approach to carbocyclic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2010, 6, No. 33, doi:10.3762/bjoc.6.33

• product containing this basic skeleton is welwitindolinone A isonitrile (4); a compound that has recently captured the attention of the synthetic community [3][4]. Spiro[cyclobutane-1,3'-indolin]-2'-ones (3, n = 0) have previously been prepared but the synthetic approach is mostly limited to simple