Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

• Praveen Reddy Adiyala,
• D. Chandrasekhar,
• Jeevak Sopanrao Kapure,
• Chada Narsimha Reddy and
• Ram Awatar Maurya

Beilstein J. Org. Chem. 2014, 10, 2065–2070, doi:10.3762/bjoc.10.214

• the synthesis of α-amino amidines has been developed using a molecular iodine-catalyzed three-component coupling reaction of isocyanides, amines, and aldehydes. The presented strategy offers the advantages of mild reaction conditions, low environmental impact, clean and simple methodology, high atom

• -aminopyridine. The desired products (amidines) were not obtained with 3-aminopyridine and 4-aminopyridine. However, we found that iodine can efficiently catalyze the three-component coupling reaction of 2-aminopyridine, aldehyde and isocyanide (Groebke–Blackburn–Bienaymé reaction) (Figure 2) [25][26][27

• -amino amidines 4 [17]. Conclusion In conclusion, we have developed a simple and clean methodology for the synthesis of substituted α-amino amidines using a three-component coupling of isocyanide, aldehyde, and aromatic amines with molecular iodine as a catalyst. The current strategy provides elegant

Tandem Cu-catalyzed ketenimine formation and intramolecular nucleophile capture: Synthesis of 1,2-dihydro-2-iminoquinolines from 1-(o-acetamidophenyl)propargyl alcohols

• Gadi Ranjith Kumar,
• Yalla Kiran Kumar,
• Ruchir Kant and
• Maddi Sridhar Reddy

Beilstein J. Org. Chem. 2014, 10, 1255–1260, doi:10.3762/bjoc.10.125

• such compounds was earlier achieved by Wang et al. through three component coupling reaction under similar conditions [13]. The method was shown to be not working for the synthesis of 4-unsubstituted adducts as the 2-aminobenzaldehyde was found to be unreactive in the given conditions and, moreover

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

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• gradient (pentane/diethyl ether 90:10 to pentane/diethyl ether 70:30) to yield the three-component coupling product 4 as a generally white solid. Possible reaction mechanism. Optimization of the reaction conditionsa. Scope of the reactiona. Acknowledgements Financial support of this work by the CNRS and

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

• , the yield of 3a increased to 79%. We examined various alkyl bromides 1 in the present radical/ionic three-component coupling reaction (Table 1). Primary alkyl bromides 1b–e containing a chlorine atom, an ester group, a cyano group, or a phenyl group worked well to give the corresponding cyanohydrin

• 3j, which possessed an olefin structure arising from the ring-opening of a cyclopropylcarbinyl radical (Table 1, entry 10) [30][31]. Conclusion In summary, we have demonstrated a three-component coupling reaction comprising alkyl bromides 1, CO and ethyl cyanoformate (2a) in the presence of Bu3SnH

• , AIBN, and Et3N, which gave moderate to good yields of cyanohydrin derivatives 3. This protocol represents a one-pot method [32][33] based on radical carbonylation and ionic cyanation. Experimental Typical procedure for radical/ionic three-component coupling reaction leading to cyanohydrin derivatives 1

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

• ], alkynes and sulfur ylides [18][19], alkynyl oxiranes [20][21][22][23][24][25][26], alkynyl ketones [27][28][29][30][31][32][33][34][35], alkynyl alcohols [36][37][38][39][40][41][42][43][44][45][46], and alkynyl ethers [47][48]. Very recently, a three-component coupling reaction toward furans catalyzed by

A³-Coupling catalyzed by robust Au nanoparticles covalently bonded to HS-functionalized cellulose nanocrystalline films

• Jian-Lin Huang,
• Derek G. Gray and
• Chao-Jun Li

Beilstein J. Org. Chem. 2013, 9, 1388–1396, doi:10.3762/bjoc.9.155

• suggested that the size of the AuNPs was about 2–3 nm and they were evenly distributed onto the surface of CNC films. Furthermore, the unique nanocomposite Au@HS-CNC catalyst displayed high catalytic efficiency in promoting three-component coupling of an aldehyde, an alkyne, and an amine (A3-coupling

• immobilized on the HS-functionalized CNCs. The novel Au@SH-CNC nanocomposite catalyst exhibited an excellent catalytic activity in the three-component coupling reaction of aldehyde-alkyne-amine (A3-coupling) either in water or without solvent, and could be used repetitively, which could reduce the cost and

• @HS-CNC (4.4 mol %) catalyst for the three-component coupling of formaldehyde, piperidine, and phenylacetylene (A3-coupling) under solvent-free conditions. Sketch illustrating preparation of the Au@HS-CNC catalyst. Three-component coupling of benzaldehyde, piperidine, and phenylacetylene catalyzed by

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• ]. As a result, Hoveyda’s zirconium-catalyzed reactions provided homobenzylmagnesium intermediates 4j, while Kambe’s titanium-catalyzed reactions afforded benzylmagnesium intermediates 4k. Kambe applied the titanocene-catalyzed reaction to a three-component coupling reaction involving a radical

• . Zirconium-catalyzed alkylmagnesiation. Titanium-catalyzed carbomagnesiation. Three-component coupling reaction. Iron-catalyzed arylzincation reaction of oxabicyclic alkenes. Reaction of allenyl ketones with organomagnesium reagent. Regio- and stereoselective reaction of a 2,3-allenoate. Three-component

• coupling reaction of 1,2-allenoate, organozinc reagent, and ketone. Proposed mechanism for a rhodium-catalyzed arylzincation of allenes. Synthesis of skipped polyenes by iterative arylzincation/allenylation reaction. Synthesis of 1,4-diorganomagnesium compound from 1,2-dienes. Synthesis of tricyclic

Tandem aldehyde–alkyne–amine coupling/cycloisomerization: A new synthesis of coumarins

• Maddi Sridhar Reddy,
• Nuligonda Thirupathi and
• Madala Haribabu

Beilstein J. Org. Chem. 2013, 9, 180–184, doi:10.3762/bjoc.9.21

• in equivalence of reductive alkylation of amines while at the same time appending an alkyne, i.e., a highly useful moiety for further functionlization. This three-component coupling has been accomplished with a very broad range of transition metals, including copper, silver, gold, ruthenium/copper

Alternaric acid: formal synthesis and related studies

• Michael C. Slade and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19

• Michael C. Slade Jeffrey S. Johnson Caudill Laboratories, Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA 10.3762/bjoc.9.19 Abstract A silyl glyoxylate three-component-coupling methodology has been exploited to achieve a formal synthesis, an

• points for application of a silyl glyoxylate three-component coupling methodology. Scheme 2 highlights three potential avenues toward the natural product and their precedents, by using the readily available (S)-2-methylbutanal (3) [27] and silyl glyoxylates 1 as two of the three key components for a

• coupling reaction. Results and Discussion Synthetic studies were initiated to explore paths a and b in Scheme 2, given the perceived rapidity with which the known intermediates could be intercepted after the proposed three-component coupling reactions. These initial studies revealed a limitation to this

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

• Elizabeth P. Jones,
• Peter Jones,
• Andrew J. P. White and
• Anthony G. M. Barrett

Beilstein J. Org. Chem. 2011, 7, 1570–1576, doi:10.3762/bjoc.7.185

• afford the more thermodynamically stable anti-adduct. Conclusion The extension of the aryne α-arylation methodology allowed for the synthesis of quaternary aryl bislactim ethers in good to excellent yields and high diastereoselectivity by means of a three-component coupling reaction in which the reaction

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• (after removal of excess acrylic acid) with the aid of an oligomeric alkyl carbodiimide 44 (Scheme 19) [19]. Interestingly, Willis and coworkers have shown that aryl N-aminosulfonamides may be accessed by three-component coupling of aryl iodides, hydrazines, and DABCO·(SO2)2 as a convenient source of

• obtained with secondary amines, the remaining N–H functionality interfering with the C–B arylation step with primary amines as coupling partners (Scheme 33). This palladium-catalyzed three-component coupling was applied to the synthesis of rolipram, which is a phosphodiesterase-4 inhibitor. In this process

PEG-embedded KBr₃: A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines

• Sanny Verma,
• Suman L. Jain and
• Bir Sain

Beilstein J. Org. Chem. 2011, 7, 1334–1341, doi:10.3762/bjoc.7.157

• the synthesis of functionalized piperidines in high yields in a one step, three component coupling between aldehyde, amine and β-keto ester. At the end of the reaction the [K+PEG]Br3− was readily regenerated from the reaction mixture by treating the residue containing [K+PEG]Br− with molecular bromine

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

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• for the addition to alkenes. The experimental studies suggest that the C–C bond-forming reaction occurs through a bimolecular reductive elimination. Furthermore, a gold-catalyzed three-component coupling was also developed for the oxidative oxyarylation of alkenes 358 via a similar strategy [170

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• introduced via a Friedel–Crafts/Mannich-type alkylation starting either from formaldehyde and dimethylamine or 2,2-dimethoxy-N,N-dimethylacetamide (Scheme 45). In a recent study a more straightforward and general copper-catalysed three component coupling leading to imidazopyridines has been reported [69

Regioselective ester cleavage during the preparation of bisphosphonate methacrylate monomers

• Kamel Chougrani,
• Gilles Niel,
• Bernard Boutevin and
• Ghislain David

Beilstein J. Org. Chem. 2011, 7, 364–368, doi:10.3762/bjoc.7.46

• –5c started from 6-aminohexanoic acid (11) and 11-aminoundecanoic acid (12), respectively. The three component coupling of 11, respectively 12, with paraformaldehyde and dimethyl phosphite furnished bisphosphonates 13 and 14 in excellent yields. These latter compounds were then reduced

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• catalytic synthetic sequence is an inexpensive and efficient route to the target compounds (Scheme 12) [64]. A three-component coupling reaction of 2-bromobenzenethiol 57, a primary amine 58 and 1-bromo-2-iodobenzenes 59, also targeting promazine derivatives 60, was successfully under palladium catalysis

One-pot three-component synthesis of quinoxaline and phenazine ring systems using Fischer carbene complexes

• Priyabrata Roy and
• Binay Krishna Ghorai

Beilstein J. Org. Chem. 2010, 6, No. 52, doi:10.3762/bjoc.6.52

• Priyabrata Roy Binay Krishna Ghorai Department of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711103, India 10.3762/bjoc.6.52 Abstract One-pot three-component coupling of o-alkynylheteroaryl carbonyl derivatives with Fischer carbene complexes and dienophiles leading to

• ] using palladium catalyzed Sonogashira coupling reactions as depicted in Scheme 2. Iodoketone 6A was prepared in 80% yield from (3-chloro-2-pyrazinyl)phenylmethanone [35] by halogen exchange with NaI in acetonitrile. The three component coupling reaction of pyrazinyl ketone 1A, carbene complex 2 and N

• quinoxaline derivative 5b as the sole product after exposure to mild acid. The three component coupling reaction of o-alkynyl quinoxaline carbonyl derivative 1C, carbene complex 2 and N-phenylmaleimide/N-methylmaleimide was also examined (Table 1, entry 3 & 4). In these cases, tandem generation and trapping

Radical carbonylations using a continuous microflow system

• Takahide Fukuyama,
• Md. Taifur Rahman,
• Naoya Kamata and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2009, 5, No. 34, doi:10.3762/bjoc.5.34

• pressurized carbon monoxide gas. Good to excellent yields of carbonylated products were obtained via radical formylation, carbonylative cyclization and three-component coupling reactions, using tributyltin hydride or TTMSS as a radical mediator. Keywords: continuous flow system; microreactor; radical

• able to obtain the desired six-membered ring lactam 8 in good yield (entry 4). Using a similar microflow system, we then carried out a three-component coupling reaction comprised of 1-iodooctane (9), CO, and methyl vinyl ketone in the presence of tributyltin hydride [24], which also worked well to give

• acyl radical traps (entries 6 and 7 ). Gratifyingly, in both cases, good yields of the three-component coupling products were formed by using reduced CO pressure. Conclusion We have developed a facile platform to conduct radical carbonylation under CO pressure in a flow system comprised of a T-shaped

Cobalt(II) chloride catalyzed one-pot synthesis of α-aminonitriles

• Surya K. De

Beilstein J. Org. Chem. 2005, 1, No. 8, doi:10.1186/1860-5397-1-8

• , efficient, and practical method for the synthesis of α-aminonitriles through a one-pot three component coupling of aldehydes, amines, and potassium cyanide using a catalytic amount of cobalt(II) chloride. The major feature of this method is that it is truly a one-pot protocol that does not need a separate