Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• under different protocols in which the stereoselectivity of the reaction can be introduced through the use of a chiral catalyst [9][10] (Lewis acid, Brønsted acids, L-proline, Cinchona alkaloids derivatives, thioureas, etc.), or by the addition of chiral amines to α,β-unsaturated esters [11][12] or the

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

• solvent-free conditions by using a planetary ball mill (Scheme 7) [46]. Cinchona-derived chiral squaramide IX, at low catalyst loading of 0.5 mol %, efficiently catalyses the solvent-free Michael reaction of acetylacetone (9) with various substituted nitroalkenes 7 in a short reaction time (5–30 minutes

• stereoselective meso-anhydride ring opening represents an important approach for providing multiple stereogenic centres in the target molecule [55][56][57]. In this feat the Cinchona alkaloids have emerged as powerful organocatalysts. A ball-milling-assisted highly efficient asymmetric ring opening of meso

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

• -cinchona bifunctional chiral organocatalyst XXXIb, the reaction of 2-mercaptobenzaldehydes 34 and α,β-unsaturated oxazolidinones 40 by a synergistic noncovalent hydrogen-bonding dual-activation strategy afforded the highly chiral thiochromenes 41 with excellent yields and enantioselectivities (Scheme 21

• unprecedented asymmetric domino thio-Michael–Michael process, involving dynamic kinetic resolution, was reported by Wang et al. [72] using cinchona alkaloid amine-thiourea XXXIb as catalyst at a low catalytic loading of 2 mol %. Reaction of 3-(2-mercaptophenyl)-2-propenoic acid ethyl esters 50 with α,β

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

• unsaturated 1,4-diketones catalyzed by thiourea and squaramide derivatives with Cinchona alkaloids afforded the formation of a new C–C bond in high yields (up to 98%) and enantiomeric purities (up to 93%). The absolute configuration of the product was suggested from comparison of the experimental and

• 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

• high. Cinchona alkaloids (Table 1, entries 1–4) catalyzed the reaction with low stereoselectivity. There was a remarkable difference in their reaction rates. Quinine (II) and quinidine (IV, Table 1, entries 2 and 4) were more efficient than cinchonine (I) and cinchonidine (III, Table 1, entries 1 and 3

Organocatalytic asymmetric Michael addition of unprotected 3-substituted oxindoles to 1,4-naphthoquinone

• Jin-Sheng Yu,
• Feng Zhou,
• Yun-Lin Liu and
• Jian Zhou

Beilstein J. Org. Chem. 2012, 8, 1360–1365, doi:10.3762/bjoc.8.157

• [26][27]. To construct the C3 quaternary stereogenic carbon center, we have designed a novel cinchona alkaloid-based phosphoramide bifunctional catalyst to realize a highly enantioselective Michael addition of both unprotected 3-alkyl- and 3-aryloxindoles to nitroolefins [28]. Based on these results

• to report our initial results about the catalytic asymmetric Michael addition of unprotected 3-prochiral oxindoles to 1,4-naphthoquinone. Results and Discussion We began the reaction development by the evaluation of different chiral catalysts derived from cinchona alkaloids in the reaction of 3

• -phenyloxindole 1a and 1,4-naphthoquinone (2a), with ethyl acetate (EtOAc) as the solvent at 0 °C (Table 1, Figure 1). A variety of bifunctional cinchona alkaloid-derived catalysts 5–9 were first tried, aiming to facilitate the reaction by the dual activation of both reaction partners, with H-bonding donor moiety

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• tosylimine 1a and β-keto acid 2a in the presence of a range of bifunctional catalysts (Table 1). We first evaluated the catalytic effects of several cinchona alkaloid derivatives. Commercially available cinchonidine (CD-1) led to the formation of the product with disappointing enantioselectivity (Table 1

• , entry 1). Quinine-derived sulfonamide [40], β-isocupreidine (β-ICD) [41][42] and biscinchona alkaloid (DHQ)2AQN were all found to be poor catalysts (Table 1, entries 2–4). On the other hand, cinchona alkaloid derived bifunctional thiourea tertiary amine catalysts afforded much improved results (Table 1

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

• Wen-Bin Yi,
• Xin Huang,
• Zijuan Zhang,
• Dian-Rong Zhu,
• Chun Cai and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138

• , Boston, MA 02125, USA 10.3762/bjoc.8.138 Abstract A fluorous cinchona alkaloid ester has been developed as a chiral promoter for the asymmetric fluorination of β-ketoesters. It has comparable reactivity and selectivity to the nonfluorous versions of cinchona alkaloids and can be easily recovered from

• the reaction mixture by simple fluorous solid-phase extraction (F-SPE) and used for the next round of reaction without further purification. Keywords: asymmetric fluorination; β-ketoester; fluorous cinchona ester; organocatalysis; recyclable chiral promoter; Introduction Fluorinated organic

• electrophilic reaction with Selectfluor (F-TEDA-BF4, 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)), as developed by Bank [7][8][9]. The Cahard [10][11][12] and Shibata [13][14] groups combined cinchona alkaloids and Selectfluor for asymmetric fluorination of substrates such as

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• immobilization of Cinchona organocatalysts using thiol–ene chemistry, in which catalyst immobilization and bead polymerization is combined in a single step. A solution of azo initiator, polyfunctional thiol, polyfunctional alkene and an unmodified Cinchona-derived organocatalyst in a solvent is suspended in

• water and copolymerized on heating by thiol–ene additions. The resultant spherical and gel-type polymer beads have been evaluated as organocatalysts in catalytic asymmetric transformations. Keywords: asymmetric catalysis; Cinchona derivatives; organocatalysis; polymerization; thiol–ene reaction

• . Such polymer beads have provided good to excellent results as organocatalysts in various asymmetric transformations [6][7]. Cinchona derivatives are used in several types of organocatalysts, and they are all equipped with a pendant vinylic functionality susceptible to activation by chemical

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• (tetrafluoroborate); TEDA = triethylenediamine) [27][28][29] marked some important discoveries: First, a new generation of highly enantioselective chiral fluorinating reagents, derived by fluorine transfer [30] from F–TEDA to the quinuclidine portion of cinchona-alkaloids, was introduced by the groups of Cahard [31

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• % yield [17]. In 2008–2009, we found that chiral nonracemic cinchona alkaloids and guanidines act as Brønsted bases to generate ammonium or guanidinium enolates for the enantioselective electrophilic trifluoromethylation of β-keto esters with Umemoto reagents with good enantioselectivities in the range 60

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• yield observed between each run and without the need for catalyst regeneration, providing 78% total yield of 14 with 88% ee. Cinchona alkaloid derivatives have been featured in a number of solid support-based continuous flow asymmetric reactions. For example, a Wang-resin supported quinine derivative

• also employed in a similar flow system for the asymmetric α-chlorination of acid chlorides (Scheme 7) [31][32]. This cinchona alkaloid derivative served the dual purpose of dehydrohalogenation and asymmetric induction, and was found to be reusable at least up to 100 times, after regeneration each time

C₂-symmetric bisamidines: Chiral Brønsted bases catalysing the Diels- Alder reaction of anthrones

• Deniz Akalay,
• Gerd Dürner,
• Jan W. Bats and
• Michael W. Göbel

Beilstein J. Org. Chem. 2008, 4, No. 28, doi:10.3762/bjoc.4.28

• exerted by chiral Brønsted bases. Moderate to excellent stereoselectivities of products 3 have been reported using pyrrolidines 4 [1][2], cyclic guanidine 5 [3], or cinchona alkaloids 6 [4] as catalysts. Recently, we could promote this type of cycloaddition by metal-free bisoxazolines 7 in up to 70% ee

Enantioselective nucleophilic difluoromethylation of aromatic aldehydes with Me₃SiCF₂SO₂Ph and PhSO₂CF₂H reagents catalyzed by chiral quaternary ammonium salts

• Chuanfa Ni,
• Fang Wang and
• Jinbo Hu

Beilstein J. Org. Chem. 2008, 4, No. 21, doi:10.3762/bjoc.4.21

• catalysts for asymmetric synthesis, cinchona alkaloids and their derivatives can catalyze an amazing array of synthetically important reactions, providing access to chiral products of high enantiopurity [32][33]. Several examples have been reported on the enantioselective incorporation of trifluoromethyl

• difluoromethylation reaction of aromatic aldehydes with Me3SiCF2SO2Ph or PhSO2CF2H in the presence of a cinchona alkaloid-based chiral quaternary ammonium salt. Results and Discussion Enantioselective nucleophilic difluoromethylation of aromatic aldehydes with Me3SiCF2SO2Ph We started our investigation with the

• ), cinchonine (CN), and cinchonidine (CD) at different reaction temperatures. We found the structure of the cinchona alkaloid had some influence on the enantioselectivity. When a cinchonine or quinidine derivative was used, the main isomer was obtained as (+)-3a, and CN 6a was superior to QD 7a. The optimized

DBFOX- Ph/metal complexes: Evaluation as catalysts for enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones

• Takehisa Ishimaru,
• Norio Shibata,
• Dhande Sudhakar Reddy,
• Takao Horikawa,
• Shuichi Nakamura and
• Takeshi Toru

Beilstein J. Org. Chem. 2008, 4, No. 16, doi:10.3762/bjoc.4.16

• reactions. Stoichiometric approaches based on cinchona alkaloid/Selectfluor® combinations [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], chiral ligand/metal-catalyzed [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] or organocatalytic [58