Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• reaction under mechanomilling [67]. Asymmetric alkynylation of prochiral sp3 C–H bonds via CDC [68]. Fe(III)-catalyzed CDC coupling of 3-benzylindoles [69]. Mechanochemical synthesis of 3-vinylindoles and β,β-diindolylpropionates [70]. Mechanochemical C–N bond construction using anilines and arylboronic

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• variety of different catalysts and their use for challenging applications have been reported over the last decades. Besides asymmetric C–C bond forming reactions the use of chiral phase-transfer catalysts for enantioselective α-heterofunctionalization reactions of prochiral nucleophiles became one of the

• major advantages of all these chiral cation-based phase-transfer catalysts (Q+ X−) is their unique potential to control the reactivity of a broad variety of different prochiral nucleophiles (i.e., enolates) via formation of chiral ion pairs, which can then undergo stereoselective α-functionalization

• reactions with different electrophiles (Scheme 1). A lot of different examples for such asymmetric α-functionalization reactions of prochiral nucleophiles under asymmetric chiral cation-based phase-transfer catalysis have been reported so far [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Besides

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• , spectrum in red). Aside from the N-methyl chemical shifts, NMR signals are otherwise indistinguishable for both epimers. This result indicated that even with prochiral C-2 of 10 being surrounded by a covalently linked chiral environment, no internal asymmetric induction took place during the reduction. The

• intermediate (not shown), instead of with a prochiral enamine intermediate (such is the case of 10). Specific rotation values ([α]D) endorsed the above mentioned configuration aspects. Comparison of the 1H NMR assignments shown by 3, 7 and 8 indicated that the extra methyl appendices on amino group had impact

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• reduction of prochiral cyclohexadienones using copper hydride generated in situ [23]. Inspired by these advances, we sought to develop an alternative and complementary method invoking the dithiane moiety as an established and easily accessible glyoxylate anion surrogate [24][25][26][27][28][29]. This would

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• prochiral carbon centers can be considered to be one of the most efficient and expedient approach [1][2][3][4]. The development of novel S-containing substrates has therefore attracted the attention of chemists [1][2][3][4]. For example in 2013, Palomo and co-workers introduced 5H-thiazol-4-ones as a new

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• processes in which a racemic starting material is irreversibly transformed into an achiral intermediate that subsequently undergoes an enantioselective conversion to the product. Reports of this type are predominantly in the areas of prochiral enolates and prochiral metal π-allyl complexes [19][20][21

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• researchers have developed methods for the stereoselective synthesis of tertiary carbon stereocenters. One aesthetically pleasing approach is the enantioselective protonation of prochiral enolates and enolate equivalents [1][2][3][4][5][6][7][8][9][10]. While an attractive strategy, the enantioselective

• -stereoselective step allows for the generation of a prochiral enolate intermediate that then undergoes enantioselective protonation (Figure 1). Two general strategies can be used when applying a conjugate addition–enantioselective protonation manifold. In the first strategy, a chiral enolate can be protonated by

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• ] pronucleophiles to γ-substituted allenoates and/or alkynoates in the presence of a C2-symmetric chiral phosphine catalyst. Although γ-substituted allenes have been employed in many phosphine-mediated γ-additions, to date there was virtually no progress on the use of prochiral pronucleophiles in phosphine-mediated

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• by the catalyst ent-6 through hydrogen-bonding interactions in a bifunctional manner. Thus, the ternary complex formed in the transition state TS5 leads to an enantioselective Friedel–Crafts-type Michael addition by the attack of indole 2 to the electrophilic prochiral center on the nitroalkene 20 in

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• prochiral ketones 35 or 36, catalyzed by a primary amine-thiourea 37 developed by Jacobsen. The proposed pathway is based on desymmetrization of 35 or 36 by an intramolecular Michael addition of the corresponding enamines to an α,β-unsaturated ester, to yield bicyclic or spiro-bicyclic products 38 and 39

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• encompass asymmetric dihydroxylation of trans-methyl cinnamate or cinnamyl alcohol [6], chiral azetidin-2,3-dione [7], asymmetric C–H amination reactions of a prochiral sulfamate [8], oxazaborolidine reduction of 3-chloropropiophenone or ketone [9], and an imidazolidin-2-one chiral auxiliary mediated

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• , in which the nitronate moiety exposes a different reactive prochiral face. These results are in good agreement with our previously reported work in which DFT calculations also showed that the difference in the steric bulk of the nitrogen substituents of the Brønsted basic site of the catalysts (the

A comprehensive study of olefin metathesis catalyzed by Ru-based catalysts

• Albert Poater and
• Luigi Cavallo

Beilstein J. Org. Chem. 2015, 11, 1767–1780, doi:10.3762/bjoc.11.192

• two prochiral faces of the C=C bond in 14–19, we always found that coordination takes places in the face that presents the two methyl groups pointing away from the NHC ligand. Of course, this results in reduced steric interactions with the NHC ligand. In the trans geometries, instead, the C=C double

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• more active form [9]. In a key step in the enantioselective synthesis of mianserin and epinastine we applied the asymmetric reduction of the prochiral imine by asymmetric hydrogen transfer reaction (ATH) [10][11][12][13][14]. The proposed strategy could be used for the preparation of the title

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• oxidative addition of Pd(0) species 5 into the aryl triflate 2 resulting in the formation of cationic complex 6. The latter can coordinate to either of the prochiral faces of dihydrofuran (1) affording diastereomeric η2-complexes 7 and 10. Subsequent carbopalladation, followed by β-hydride elimination

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

• . This led to the development of stereoselective methodologies and the synthesis of compounds with various biological properties [1]. In particular, the high reactivity of the C-3 prochiral carbonyl group allows the easy transformation of isatin into 2-oxindole derivatives, mostly by nucleophilic

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• reduction of a prochiral ketone. The phosphoramidate (Scheme 32-iii) was the most efficient catalyst for these two reactions (ee: 95–98%, conversion 87–98%). In relation with asymmetric synthesis, the determination of the enantiomeric excess (ee) is usually achieved by different methodologies including

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• oxazolone 5aa and NPM catalyzed by [(Sa)-Binap-AuTFA]2. In previous works, we have demonstrated that the stereoselectivity of the 1,3-DC employing chiral metallic Lewis acids arises from the blockage of one of the prochiral faces [34]. Starting from this selected conformation of the catalyst, our results

• show that the (2Re,5Re) prochiral face is less hindered than the other prochiral face in the most stable conformation of [{(Sa)-Binap-Au}2]-5aa complex (Figure 3). As expected, the existence of dimeric gold units is crucial in the blockage of one of the prochiral faces, and therefore, in the

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

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

• rotation–reflection axis (Figure 1). Usually, a prochiral or meso-molecule can be converted into a chiral molecule in a single step [4][5][6] in the presence of chiral catalysts. Therefore, enantioselective desymmetrization is regarded as a very powerful strategy for producing a large amount of chiral

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

• -hydroxycoumarin (1) to prochiral α,β-unsaturated ketones. Instead of acid additives, which sometimes lead to decomposition of sensitive components [18], alkali-metal ions are employed as very mild Lewis acids (Scheme 1). The activation of Michael acceptors by iminium ions enables asymmetric additions of 4

• , which are able to form imine complexes with prochiral α,β-unsaturated ketones, which could be detected by ESIMS spectrometry in an exemplary case. It was found that the Lewis acidities of the alkali metal ions are strong enough to activate the imine homologous Michael systems for nucleophilic addition

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

• chiral or prochiral carbon electrophiles may constitute part of the overall stereodifferentiating process. The potential of differentiating the faces of a prochiral electrophile can be quantified for Lewis bases through affinity numbers to a prochiral reference cation. The potential of this approach has

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

• Michael addition of unprotected 3-prochiral oxindoles 1 to 1,4-naphthoquinone. Quinidine derivative (DHQD)2PYR was found to be able to catalyze this reaction in up to 83% ee, with moderate to excellent yields. This method could be used for the synthesis of enantioenriched 3,3-diaryloxindoles, and the

• enantioenriched 3-hydroxyoxindoles [22][23][24]. For the synthesis of chiral 3-aminooxindoles, we developed the first example of catalytic asymmetric addition of nucleophiles to isatin-derived ketoimines using TMSCN [25] and the amination of unprotected 3-prochiral oxindoles using di-tert-butyl azodicarboxylate

• -diaryloxindoles. It also came to our attention that, while the addition of 3-prochiral oxindole to a variety of Michael acceptors had been studied [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], the use of quinones as the Michael acceptor had not been realized. Therefore, in this letter we are going

Cyclodextrin nanosponge-sensitized enantiodifferentiating photoisomerization of cyclooctene and 1,3-cyclooctadiene

• Wenting Liang,
• Cheng Yang,
• Masaki Nishijima,
• Gaku Fukuhara,
• Tadashi Mori,
• Andrea Mele,
• Franca Castiglione,
• Fabrizio Caldera,
• Francesco Trotta and
• Yoshihisa Inoue

Beilstein J. Org. Chem. 2012, 8, 1305–1311, doi:10.3762/bjoc.8.149

• chirality transfer from chiral host to prochiral substrate through the long-lasting intimate supramolecular contacts of guest substrate(s) with the chiral host in both the ground and excited states [4][5][6][7][8][9][10]. Various types of chiral supramolecular hosts, including modified zeolites [11

Synthesis and structure of tricarbonyl(η⁶-arene)chromium complexes of phenyl and benzyl D-glycopyranosides

• Thomas Ziegler and
• Ulrich Heber

Beilstein J. Org. Chem. 2012, 8, 1059–1070, doi:10.3762/bjoc.8.118

• (MeCN)3Cr(CO)3 were also unsuccessful (no further experimental details shown). Next, we also prepared some sugar-derived tricarbonylchromium complexes of glycosides having a prochiral aglycon, i.e., an ortho-substituted phenyl or benzyl aglycon. Glycosides 1m [21] and 1q [22] were prepared according to

• Ar and exclusion of light. Synthesis of tricarbonylchromium complexes 2m–q from glycosides 1m–q containing a prochiral aglycon and Cr(CO)6 in di-n-butylether/THF 9:1 at 140 °C under Ar in the dark. Chemical shifts (δ in ppm) of the protons of compounds 1a and 2a derived from the 1H NMR spectra of the

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• reported a type of NHC–Au(I) complexes 2 containing C2-symmetric bis(NHC)-ligands with two imidazolin-2-ylidene moieties on a chiral dioxolane backbone, produced in up to 95% ee by hydrogenation of a prochiral alkene [11]. Recently, Toste and co-workers reported a novel family of axially chiral (acyclic