Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• , potassium channel, mPGES-1, and tubulin inhibitors, as well as the immunomodulatory drug thalidomide [28][29][30][31][32] (Figure 1). Results and Discussion Our initial effort was focused on the development of reaction conditions for the one-pot double [3 + 2] cycloadditions. The first [3 + 2] cycloaddition

• . Upon the completion of the reaction as monitored by LC–MS, the reaction mixture was concentrated and then isolated on a semi-preparative HPLC with a C18 column to afford purified product 1. Heterocyclic fragments in bioactive compounds. One-pot double [3 + 2] cycloadditions and denitrogenation for

Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

• Yasuhiro Yamashita,
• Susumu Yoshimoto,
• Mark J. Dutton and
• Shū Kobayashi

Beilstein J. Org. Chem. 2016, 12, 1447–1452, doi:10.3762/bjoc.12.140

• Yasuhiro Yamashita Susumu Yoshimoto Mark J. Dutton Shu Kobayashi Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan 10.3762/bjoc.12.140 Abstract Highly efficient catalytic asymmetric [3 + 2] cycloadditions using a chiral copper amide are reported

• developed asymmetric [3 + 2] cycloadditions [4][5][6][7][8] and asymmetric Mannich-type reactions [9] by using chiral silver or copper amides as catalysts. In these reactions, it has been revealed that the metal amides have higher activity than typical silver or copper acid/base catalysts, and that less

• reactive substrates react smoothly to afford the desired products in high yields with high stereoselectivities. Based on these results, it was considered that metal amide catalysts might also achieve high catalyst turnover. Here, we report chiral copper amide-catalyzed asymmetric [3 + 2] cycloadditions of

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• 1,5-diradical as a key intermediate. The complete change of the reaction mechanism toward the concerted [3 + 2]-cycloaddition was observed in the reaction of a sterically crowded cycloaliphatic thiocarbonyl ylide with ferrocenyl methyl thioketone. Keywords: [3 + 2]-cycloadditions; 1,3-dithiolanes

• -tetrasubstituted 1,3-dithiolanes [6][7], cycloaliphatic S-methanides tend to form mixtures of both regioisomeric cycloadducts with the major component being the sterically more crowded isomer [7][8]. In a recent study, we proposed a diradical mechanism for the [3 + 2]-cycloadditions of thiocarbonyl S-methanides

• [3 + 2]-cycloadditions. The high reactivity of ferrocenyl thioketones is demonstrated by the fact that no products of competitive reactions, such as dimerization of the intermediate 1,3-dipole or 1,3-dipolar electrocyclizations, were observed. Based on these observations one can expect that

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

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• . Remarkably, in no single case, the ‘head-to-head dimerization’ of aryl/hetaryl and dihetaryl substituted thiocarbonyl ylides was observed. Keywords: [3 + 2]-cycloadditions; diazoalkanes; diradicals; 1,3-dithiolanes; reaction mechanisms; thioketones; Introduction Cycloaddition reactions belong to the most

• important classes of organic reactions, and [3 + 2]- cycloadditions, also known as 1,3-dipolar cycloadditions or Huisgen reactions, offer a universal tool for the preparation of five-membered heterocycles with a variable number of heteroatoms in the ring [1][2]. In addition to their practical importance

• , discussions on the mechanism contribute significantly to the development of fundamental concepts in organic chemistry [3][4][5][6][7]. The first general concept of concerted [3 + 2]-cycloadditions was formulated by Huisgen [4]. However, some time later, Huisgen and co-workers reported stepwise [3 + 2

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• interaction and may promote the formation of metal nanoparticle clustering. Cu(I)-based system have been used in alkyne/azide [3 + 2] cycloadditions, while Pd(II)-based catalysts have been used in C–C couplings reactions (Scheme 7) [34]. An example of water-soluble β- and γ-CD/chitosan derivatives have been

Three-component synthesis of C₂F₅-substituted pyrazoles from C₂F₅CH₂NH₂·HCl, NaNO₂ and electron-deficient alkynes

• Pavel K. Mykhailiuk

Beilstein J. Org. Chem. 2015, 11, 16–24, doi:10.3762/bjoc.11.3

• 14 failed. These results suggest that the reaction between C2F5CHN2 and alkynes belongs to type I of [3 + 2] cycloadditions [49]: It is accelerated by the alkyne`s EWGs and decelerated by EDGs. Next diverse disubstituted alkynes 15–22 (Table 3) with at least one strong EWG (–CO2Alk or –COAlk) were

• C2F5CHN2 vs CF3CHN2 To compare the reactivities of C2F5CHN2 and CF3CHN2 in [3 + 2] cycloadditions with alkynes, one must take into account two factors: steric and electronic [49]. On one hand, the C2F5 substituent is bulkier than the CF3 one, decreasing thereby the reactivity of C2F5CHN2 compared with

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

• Chunpu Li,
• Lei Zhang,
• Shuangjie Shu and
• Hong Liu

Beilstein J. Org. Chem. 2014, 10, 2441–2447, doi:10.3762/bjoc.10.254

• Ullmann condensation is a powerful method for C–N coupling [24][25][26], especially the N-arylation of nitrogen-containing heterocycles such as indoles [27][28]. Indolo[1,2-a]quinazoline is a kind of tetracyclic compounds containing the indole motif that has been constructed by intramolecular [3 + 2

• ] cycloadditions of azido-ketenimines and azido-carbodiimides (Scheme 1) [29]. The available starting materials for the synthesis of these compounds, however, are limited. Very recently, Perumal [30] reported an efficient method for the synthesis of indolo[1,2-a]quinazoline through a Cu(I)-catalyzed intramolecular

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• synthesized a series of ferrocene-modified planar chiral phosphines featuring a new skeleton (Figure 3) [44][45]. Among these compounds, the P-cyclohexyl phosphine C1 proved to be the most efficient catalyst for [3 + 2] cycloadditions of ethyl 2,3-butadienoate with activated enones, fumarate esters, and

• methylenebenzofuranone derivatives, constructing a variety of complex polysubstituted spirocyclopentenebenzofuranones in high yields with good to excellent enantioselectivities [75]. Using the amino acid-derived chiral phosphine H2, Lu and co-workers explored asymmetric [3 + 2] cycloadditions between MBH carbonates and

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• side electronically more favorable for a nucleophilic attack. Prato reaction Cycloadditions to the π-system constitute another major family of fullerene reactions. In particular, 1,3-dipolar reagents readily add to the 6:6-bond of fullerene C60, which acts as a good dipolarophile. Among such [3 + 2

• ] cycloadditions, the reaction with azomethine ylides has found great popularity, because it leads to versatile pyrrolidine derivatives of C60. The sources of the ylide can be iminium salts, aziridines, oxazolidines or silylated iminium compounds. In 1993, Prato and coworkers developed the protocol that is now

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• methods that affords optically active cyclooctanes by means of a catalytic enantioselective process. Also recently, Chen and co-workers demonstrated that gold-activated allenamide species can participate in [3 + 2] cycloadditions with azomethine imines or nitrones under catalysis with Ph3PAuCl/AgOTf or

• + 2] cycloadditions of allenamides. Mechanistic rational for the gold-catalyzed [2 + 2] cycloadditions. Enantioselective cascade cycloadditions between allenamides and oxoalkenes. Enantioselective [3 + 2] cycloadditions of nitrones and allenamides. Enantioselective formal [4 + 3] cycloadditions

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• Materiais Inorgânicos, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Rio Grande do Sul, RS, Brazil 10.3762/bjoc.9.96 Abstract Chiral nonracemic aminated nitroso acetals were synthesized via diastereoselective multicomponent [4 + 2]/[3 + 2] cycloadditions employing new (S,E)-γ-nitrogenated

• [3 + 2] cycloadditions, we believe that in the TS the respective nitronates present a half-chair conformation with the HC(4) substituent and the alkoxy group in an axial position to maximize the stabilization generated by the anomeric effect [9][33][41][42]. Thus, the competitive endo/exo approach of

• 14c in 50% yield (Scheme 4). Pyrrolizidin-3-one frameworks are important precursors of pyrrolizidine nuclei, which are largely widespread in nature, mainly in the form of pyrrolizidine alkaloids [43]. Conclusion In summary, the multicomponent [4 + 2]/[3 + 2] cycloadditions using a new class of chiral

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

• nucleophiles [5][6][7][8][9][10], in Friedel–Crafts alkylations [11][12][13][14], and Baylis–Hillman reactions [15][16][17][18]. Furthermore, nitroalkenes can react as dipolarophiles in [3 + 2] cycloadditions [19][20][21][22], as dienophiles in [4 + 2] cycloadditions [23][24][25][26], and as heterodienes in

Photochemical and thermal intramolecular 1,3-dipolar cycloaddition reactions of new o-stilbene-methylene-3-sydnones and their synthesis

• Kristina Butković,
• Željko Marinić,
• Krešimir Molčanov,
• Biserka Kojić-Prodić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2011, 7, 1663–1670, doi:10.3762/bjoc.7.196

• ), nitrosation and ring closure with acetic acid anhydride (30 and 40% yield). The products were submitted to photochemical and thermal intramolecular [3 + 2] cycloadditions to afford diverse heteropolycyclic compounds. Photochemical reactions afforded cis-3-(4-methylphenyl)-3a,8-dihydro-3H-pyrazolo[5,1-a

• . Illustration of intramolecular [3 + 2] cycloadditions. Styryl-sydnone 1 and stilbenyl sydnone 2 and their photoproducts F and G, respectively; target molecules 3 in this work. ORTEP of compound 14. Proposed stereochemical pathway of sydnone ring (CH–N) and trans- and cis-stilbene (α–β). Proposed stereochemical

• pathway of sydnone ring (N–CH) and trans- and cis-stilbene (α–β). Thermal and photochemical intermolecular [3 + 2] cycloadditions. Synthesis of the target molecules 3a and 3b. Photolysis of cis- or trans-3. Aromatization with DDQ. Possible mechanism for the formation of the photoproducts. Thermal reaction

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• cycloadditions is the initial nucleophilic addition of a carbonyl oxygen to the alkyne. As expected, an imine can also be used as a nucleophile, such as 15, which leads to the generation of an azomethine ylide capable of participating in dipolar (3 + 2) cycloadditions to unsaturated systems such as electron-rich

• gold species of type XXIII may be sometimes similar to that of other transition metal carbenoids or even to that of alkenyl Fischer carbenes. However, in many other cases, it is markedly different. For instance, while alkenyl Fischer carbenes act as two-carbon atom components in (3 + 2) cycloadditions

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

• + 3] [106][107][108] cycloaddition reactions have been developed in last 3 years. Treatment of 1-aryl-1-allen-6-enes 220 with [PPh3AuCl]/AgSbF6 (5 mol %) in CH2Cl2 at 25 °C led to intramolecular [3 + 2] cycloadditions to afford cis-fused dihydrobenzo[a]fluorenes 221 efficiently and selectively [99

Brønsted acid-promoted azide–olefin [3 + 2] cycloadditions for the preparation of contiguous aminopolyols: The importance of disiloxane ring size to a diastereoselective, bidirectional approach to zwittermicin A

• Hubert Muchalski,
• Ki Bum Hong and
• Jeffrey N. Johnston

Beilstein J. Org. Chem. 2010, 6, 1206–1210, doi:10.3762/bjoc.6.138

Total synthesis of (±)-coerulescine and (±)-horsfiline

• Mukund G. Kulkarni,
• Attrimuni P. Dhondge,
• Sanjay W. Chavhan,
• Ajit S. Borhade,
• Yunnus B. Shaikh,
• Deekshaputra R. Birhade,
• Mayur P. Desai and
• Nagorao R. Dhatrak

Beilstein J. Org. Chem. 2010, 6, 876–879, doi:10.3762/bjoc.6.103

• include the following oxidative rearrangements: lead tetraacetate [3], sodium tungstate [11], tert-butyl hypochlorite [12] and N-bromosuccinimide [13]. Other approaches involve the Mannich reaction [14], ring expansion reactions [15][16], 1,3-dipolar [3 + 2] cycloadditions [17][18][19], intramolecular