Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• emerged as a cutting-edge approach in recent years. This review summarizes the origin and recent developments of enantioselective desymmetrization of meso-aziridines and meso-epoxides in the presence of organocatalysts. Keywords: aziridine; desymmetrization; enantioselectivity; epoxide; organocatalysis

• -oxide, and N-heterocyclic carbenes were published. However, the enantioselective ring-opening of meso-aziridines in the presence of chiral organocatalysts (OC) has emerged as a research field only in recent years. The organocatalysts utilized in these processes are diverse in their structural features

• organocatalysts. Cinchona alkaloid derivatives The first organocatalytic enantioselective desymmetrization of meso-aziridines was discovered by Hou and co-workers in 2007 [40] with various arylthiols as nucleophiles in CCl4 at 0 °C in the presence of cinchonine-derived phase-transfer catalysts (PTCs, Figure 2, OC

The rapid generation of isothiocyanates in flow

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 1613–1619, doi:10.3762/bjoc.9.184

• which has received less attention are isothiocyanates. These species are widely utilised as valuable starting materials for many thiourea-based organocatalysts [24][25][26], numerous heterocyclic entities [27][28][29] as well as important entry points towards other key functional groups such as

Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

• Qiang Wei,
• Ya-Yi Wang,
• Yu-Liu Du and
• Liu-Zhu Gong

Beilstein J. Org. Chem. 2013, 9, 1559–1564, doi:10.3762/bjoc.9.177

• ]. These leading findings indicate that either Lewis base or Brønsted acid shows catalytic activity for the selenofunctionalization reaction. Since chiral phosphoric acids have been shown to be Brønsted acid/Lewis base bifunctional organocatalysts [29][30][31][32][33], we ask whether the chiral BINOL-based

Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

• Carsten S. Kramer and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 1414–1418, doi:10.3762/bjoc.9.158

• -Leopoldshafen, Germany 10.3762/bjoc.9.158 Abstract A variety of organocatalysts were screened for the catalysis of the naphthoquinone monoketal Diels–Alder reaction. In this study we found that Schreiner's thiourea catalyst 10 and Jacobson's thiourea catalyst 12 facilitate the cycloaddition of the sterically

• organocatalysts were found to accelerate a variety of reactions. Due to the value of the Diels–Alder reaction for the synthetic community, different organocatalysts have been developed to catalyze this atom-economical cycloaddition in a highly enantioselective fashion. Thereby, chiral amines, heterocyclic

• carbenes, guanidines, thioureas, amidinium ions, diols, and Brønsted acids showed their value to give densely functionalized Diels–Alder products in high selectivities [1][2][3][4][5][6][7]. In addition, some organocatalysts enabled even the formation of quaternary centers in Diels–Alder cycloadditions [3

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• Abstract Since the beginning of the century, N-hydroxyphthalimide and related compounds have been revealed to be efficient organocatalysts for free-radical processes and have found ample application in promoting the aerobic oxidation of a wide range of organic substrates. When combined with different co

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

• -nitrostyrene and its phenyl-substituted analogues, besides the heteroaromatic nitroalkenes, have been employed widely in highly enantioselective syntheses promoted by chiral metallic catalysts [33][34][35][36][37] and most recently by a great number of different chiral organocatalysts [38][39][40][41] or

• derivatives by the use of chiral metal and organocatalysts [55][56]. In contrast, chiral 1,3-nitroamines, despite constituting direct precursors of chiral 1,3-diamines, are scarcely synthesized by conjugate addition of nitroalkanes to nitroalkenes. Chiral 1,3-diamines present extraordinary opportunities in

Synthesis and structure of trans-bis(1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene)palladium(II) dichloride and diacetate. Suzuki–Miyaura coupling of polybromoarenes with high catalytic turnover efficiencies

• Jeelani Basha Shaik,
• Venkatachalam Ramkumar,
• Babu Varghese and
• Sethuraman Sankararaman

Beilstein J. Org. Chem. 2013, 9, 698–704, doi:10.3762/bjoc.9.79

• -triazolylidene; Introduction Over the past decade N-heterocyclic carbenes (NHCs) have attracted the attention of synthetic and organometallic chemists tremendously [1][2][3][4][5]. NHCs have been proven to be useful as organocatalysts in organic synthesis [6][7][8][9]. They are excellent ligands for transition

1-n-Butyl-3-methylimidazolium-2-carboxylate: a versatile precatalyst for the ring-opening polymerization of ε-caprolactone and rac-lactide under solvent-free conditions

• Astrid Hoppe,
• Faten Sadaka,
• Claire-Hélène Brachais,
• Gilles Boni,
• Jean-Pierre Couvercelle and
• Laurent Plasseraud

Beilstein J. Org. Chem. 2013, 9, 647–654, doi:10.3762/bjoc.9.73

• (DMC) with imidazole derivatives, making them very attractive and accessible compounds [35]. Therefore, they found applications as ligands in organometallic catalysis [36][37][38][39][40][41], as precursors of halide-free ionic liquids [42][43][44][45], and as organocatalysts in reactions involving

NHC-catalysed highly selective aerobic oxidation of nonactivated aldehydes

• Lennart Möhlmann,
• Stefan Ludwig and
• Siegfried Blechert

Beilstein J. Org. Chem. 2013, 9, 602–607, doi:10.3762/bjoc.9.65

• of aldehydes to the corresponding acids or esters. The reaction proceeds under metal-free conditions by using N-heterocyclic carbenes as organocatalysts in combination with environmentally friendly oxygen as the terminal oxidation agent. Keywords: aerobic oxidation; chemoselective oxidation; metal

Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

• Matthias Leven,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2013, 9, 155–165, doi:10.3762/bjoc.9.18

• vitamin K antagonist, and the dissimilar activity of the enantiomers is well documented in the literature [30][31][32]. The organocatalytic synthesis of warfarin has already been tested with several organocatalysts. Diphenylglycinol derivatives and derivatives of 1,2-diphenylethane-1,2-diamine provided

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• amplified in recent times. In this regard, catalytic asymmetric synthesis involving the use of chiral organocatalysts has emerged as a powerful tool from the infancy to the maturity of asymmetric organocatalysis [13][14][15][16][17][18][19][20][21][22][23][24][25][26]. The use of organocatalysts for

• . Organocatalyts also provide an insight into biological catalytic processes, as a number of these catalysts work by the phenomenon of enzyme mimicry. These advantages of chiral organocatalysts also meet many of the requirements of green chemistry [27]. Recently developed, organocatalytic asymmetric

• various bioactive molecules [28]. Among different organocatalysts used for asymmetric aldol reactions, proline and its derivatives emerged as powerful catalysts for the enamine activation of donor aldehyde or ketone. Bolm’s group reported a solvent-free asymmetric organocatalytic aldol reaction under ball

Design and synthesis of a photoswitchable guanidine catalyst

• Philipp Viehmann and
• Stefan Hecht

Beilstein J. Org. Chem. 2012, 8, 1825–1830, doi:10.3762/bjoc.8.209

• ]. Metal-based catalysts as well as organocatalysts have been widely studied in the ROP of lactide [15]. Guanidines, and especially 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), have proven to be very powerful in this context (Scheme 1) [16]. However, due to the discussion of several polymerization mechanisms

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• addition of enolizable aldehydes to maleimides in the original method suggested the possibility of producing chiral γ-lactams through the use of a chiral proline-like organocatalysts. In fact, Córdova and co-workers have previously established a protocol for such a process [13]. Based on this initial

Imidazolinium and amidinium salts as Lewis acid organocatalysts

• Oksana Sereda,
• Nicole Clemens,
• Tatjana Heckel and
• René Wilhelm

Beilstein J. Org. Chem. 2012, 8, 1798–1803, doi:10.3762/bjoc.8.205

• and amidinium salts as soft Lewis acid organocatalysts is described. These salts were suitable catalysts for the activation of unsaturated thioesters in a Diels–Alder reaction and in the ring opening of thiiranes and epoxides. The products were isolated in good yields. The mild catalysts did not cause

• that bis-imidazolinium salts can be applied as Lewis acid organocatalysts to activate a thiocarbonyl group. Next, the behavior of these salts in the ring opening of a thiirane was explored. No activity was observed with salt 9 in the ring opening with aniline. Therefore, the more active bis

• transformed directly by anion metathesis to the salt 21. Conclusion It was possible to prepare new metal-free Lewis acids containing bis-imidazolinium cations and investigate the salts as organocatalysts. Although with enantiopure chiral salts no enantiomeric excess was observed, it was shown for the first

Asymmetric desymmetrization of meso-diols by C₂-symmetric chiral 4-pyrrolidinopyridines

• Hartmut Schedel,
• Keizo Kan,
• Yoshihiro Ueda,
• Kenji Mishiro,
• Keisuke Yoshida,
• Takumi Furuta and
• Takeo Kawabata

Beilstein J. Org. Chem. 2012, 8, 1778–1787, doi:10.3762/bjoc.8.203

• pyrrolidinopyridine framework as a catalytic site. Some of these organocatalysts effectively promoted asymmetric desymmetrization of meso-diols via enantioselective acylation. Keywords: acylation; desymmetrization; hydrogen bond; meso-diol; nucleophilic catalyst; organocatalysis; Introduction Since the pioneering

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• /hemiacetal sequence with chiral or achiral secondary amines as organocatalysts. Thus, a series of achiral pyrazolidine derivatives were obtained with good yields (up to 90%) and high diastereoselectivities (>20:1) with pyrrolidine as an organocatalyst, and enantioenriched pyrazolidines are also achieved with

• investigated in the presence of several common secondary amines 1a–f as organocatalysts in chloroform. Pyrrolidine (1c) turned out to be an effective catalyst and di-tert-butyl hydrazine-1,2-dicarboxylate (2c) was a potent donor (see Table S1 in the Supporting Information File 1). When di-tert-butyl hydrazine

• -Michael/hemiacetal reaction. Initially, a series of readily available chiral organocatalysts 1g–o were chosen and investigated for the domino aza- Michael/hemiacetal reaction of disubstituted hydrazine 2c and 4-nitrocinnamaldehyde (3a) under catalytic loading of 20 mol % in CH2Cl2 at room temperature. The

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• thiochromenes; and (3) Organocatalytic aza-Michael reactions to access functionalized 1,2-dihydroquinolines, using chiral proline and its derivatives (Figure 2), chiral bifunctional thioureas, cinchona alkaloids and other organocatalysts (Figure 3). For each reaction, the initial screening result of various

• organocatalysts with their percentage of conversion (% yield) and enantiomeric excess (ee) is presented in tabular form, and the best catalyst is used for the given individual scheme. Review 1 Organocatalytic oxa-Michael additions to access functionalized chromenes 1.1. Reactions of 2-hydroxybenzaldehydes with

• pyrrolidine-triazole-based C2 symmetric organocatalysts XXVIIa was reported by Sankararaman et al. [61] for the asymmetric synthesis of nitrochromenes 30 (Scheme 15). The reaction gave poor enantioselectivities both in toluene (15% ee) and in DMF (24% ee). In 2010, Das et al. [62] reported an organocatalytic

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• ; Introduction In recent years bifunctional compounds have found frequent applications as organocatalysts in modern synthetic organic chemistry [1][2][3][4][5][6][7][8]. Over the past decade, different catalytic methodologies have been reported that use chiral thiourea-based bifunctional molecules [9][10][11][12

• ][13]. In particular, remarkable progress has been made in the development of secondary and tertiary amine-thiourea bifunctional organocatalysts for a great number of useful transformations [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Recently, the Tsogoeva

• group and that of Jacobsen reported the first successful application of primary amine-thiourea organocatalysts with the synchronous dual activation of a nucleophile and an electrophile in nitro-Michael addition reactions [36][37][38][39][40][41][42]. Bifunctional organocatalysts that contain both a

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• range –10 < E < –5 were determined for iminium ions derived from cinnamaldehyde and common organocatalysts, such as pyrrolidines and imidazolidinones, by studying the rates of their reactions with reference nucleophiles. Iminium activated reactions of α,β-unsaturated aldehydes can, therefore, be

• settled by studying the reactivities of independently synthesized intermediates. Kinetic investigations of the reactions of N-heterocyclic carbenes (NHCs) with benzhydrylium ions showed that they have similar nucleophilicities to common organocatalysts (e.g., PPh3, DMAP, DABCO) but are much stronger (100

• ]. Quantitative aspects of N-heterocyclic carbene (NHC) catalysis As the following discussion will focus on the difference between the kinetic term “nucleophilicity” and the thermodynamic term “Lewis basicity”, let us first illustrate this aspect by comparing the behavior of two well-known organocatalysts, 1,4

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• investigated the organocatalytic approach to the asymmetric desymmetrization of the title compounds with malonates. Three types of organocatalysts providing noncovalent interactions were used for this purpose: Cinchona alkaloids (I–V), thiourea derivatives (VI, VII) and squaramide derivatives (VIII, IX

• yields (up to 99%) and in high enantioselectivities (up to 93%). This enantioselective 1,4-addition to unsaturated 1,4-diketones affords valuable intermediates for further synthetic transformations. The conjugated addition to unsaturated 1,4-diketone 1. Organocatalysts screened. Proposed transition state

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• Marcus Frings Isabelle Thome Carsten Bolm Institut für Organische Chemie, Landoltweg 1, RWTH Aachen University, 52074 Aachen, Germany 10.3762/bjoc.8.164 Abstract For the first time, chiral sulfoximine derivatives have been applied as asymmetric organocatalysts. In combination with a thiourea-type

• backbone the sulfonimidoyl moiety leads to organocatalysts showing good reactivity in the catalytic desymmetrization of a cyclic meso-anhydride and moderate enantioselectivity in the catalytic asymmetric Biginelli reaction. Straightforward synthetic routes provide the newly designed thiourea-sulfoximine

• reactions in a highly enantioselective manner has no end in sight. In this context, thiourea-based organocatalysts have caught significant attention due to their ability to activate substrates through hydrogen-bonding [42][43][44][45][46][47]. Usually, these chiral thioureas are classified into several

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• : "MP2-5") reproduce results obtained at the G3 level within 4.0 kJ/mol for selected small and medium-sized organocatalysts [5]. For pyridine (1) the MCA value obtained with this model amounts to MCA(1) = +518.7 kJ/mol, which is only 0.5 kJ/mol lower than the G3 value. The following discussion will thus

• 109 times more nucleophilic. This is in agreement with the MCA values for 341 and 342, which are approx. 50 kJ/mol higher compared to the value of 334. However, including other typical organocatalysts such as PPh3 (89), DMAP (54), and DBU (60) in the comparison of MCA- and N-values, Mayr et al. note

• collected in Table 9. The benzhydryl cation affinities (BHCA) of weak nucleophiles like ammonia (344) and phosphane (343) are less than 100 kJ/mol and thus much smaller than the respective MCA values. In contrast, often used organocatalysts like 4-dimethylaminopyridine (54), PPY (56), and PPh3 (89) possess

Highly enantioselective access to cannabinoid-type tricyles by organocatalytic Diels–Alder reactions

• Stefan Bräse,
• Nicole Volz,
• Franziska Gläser and
• Martin Nieger

Beilstein J. Org. Chem. 2012, 8, 1385–1392, doi:10.3762/bjoc.8.160

• fine chemicals, were either transition-metal complexes or enzymes. In the past few years, however, organocatalysis has emerged as an alternative approach for the catalytic production of enantiomerically pure organic compounds [15][16]. These organocatalysts have several important advantages. They are

• , organocatalytic methods are especially attractive for the preparation of compounds that do not tolerate metal contamination, e.g., active pharmaceutical ingredients. MacMillan’s imidazolidinone-based organocatalysts are general catalysts for a variety of asymmetric transformations. The first highly

• performed a catalyst screening with the previously synthesized imidazolidinone catalysts 15 to study their asymmetric induction (Scheme 5). As starting material we used compound 17 with the THC-typical pentyl side chain. The results are summarized in Table 5. The used organocatalysts, having a (S

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• non-asymmetric and asymmetric C–H activation reactions mediated by organocatalysts are discussed in this review. Keywords: asymmetric; C–H activation; non-asymmetric; organocatalysis; organocatalytic; Introduction C–H activation reactions have recently been found to be a powerful method for the

• activation is well-known in the literature [26][27][28][29][30]. Stoichiometric amounts of a radical source, such as tributyltin hydride and tris(trimethylsilyl)silicon hydride [31], or irradiation [32] were also utilized for biaryl synthesis from unactivated arenes. However, organocatalysts have not been

• ongoing. Conclusion In summary, this review highlights the recent developments of organocatalytic C–H activation reactions. Organocatalysts have been involved in 1,5-hydride shift and decarboxylative/non-decarboxylative redox-amination processes. Asymmetric organocatalytic C–H activation reactions have

Organocatalysis

• Benjamin List

Beilstein J. Org. Chem. 2012, 8, 1358–1359, doi:10.3762/bjoc.8.156

• -molecular-weight organic compounds, in which a metal is not part of the active principle. Organocatalysts donate or remove electrons or protons as their activation mode, hence defining four distinct subareas: Lewis base and Lewis acid catalysis on the one hand, and Brønsted base and Brønsted acid catalysis