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

• tetrahydroisoquinoline derivatives were synthesized using a pyridine-based chiral ligand (PyBox, Scheme 12) in the presence of DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone). The coupling products were isolated in fair yields with ee’s (enantiomeric excesses) up to 79%. The milling copper balls were also identified as

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• byproducts (Scheme 32). Chiral 3-aryl-1-indanones 107 have been synthesized via rhodium-catalyzed asymmetric cyclization of pinacolborane chalcone derivatives 105 using (R)-MonoPhos® as a chiral ligand [58]. In this reaction, a wide variety of 1-indanones 107 were obtained in high yields and up to 95

Copper-catalyzed asymmetric sp³ C–H arylation of tetrahydroisoquinoline mediated by a visible light photoredox catalyst

• Pierre Querard,
• Inna Perepichka,
• Eli Zysman-Colman and
• Chao-Jun Li

Beilstein J. Org. Chem. 2016, 12, 2636–2643, doi:10.3762/bjoc.12.260

• salts and PhPyBox as chiral ligand have demonstrated its efficiency producing good enantioselectivity and tolerated a fairly diverse substrate scope. We envisioned that this visible light-mediated asymmetric arylation reaction could be extended to other sp3 C–H bonds. The development of new light

• ), [Ir(ppy)2(dtbbpy)]PF6 (0.001 mmol), CuBr2 (0.02 mmol), DCE (0.5 mL), under argon atmosphere. Design light-mediated arylation of THIQs. Evaluation of chiral ligands. Proposed reaction mechanism. Optimization of reaction conditionsa. Effect of chiral ligand on the enantioselectivity of coupling of N

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• presence of catalyst, etc. Further, the regioselectivity can be influenced by the reversible nature of the hetero-Diels–Alder reaction (i.e., thermodynamic control). This was demonstrated by Miller in both higher temperature and Cu(I)-mediated hetero-Diels–Alder reactions of a chiral ligand with nitroso

• complementary chiral ligand, was sufficient to alter the regioselectivity for the reaction between the piperidinyl-substituted diene 111 and 2-methyl-6-nitrosopyridine (112). By increasing the concentration of tetrakis(acetonitrile)copper(I)hexafluorophosphate, the regioselectivity of the major product 113 was

• -cyclohexadiene 196 with the substituted pyridylnitroso species 195 with (S)-SEGPHOS (198) as the chiral ligand gave the best results. An excellent regioselectivity towards distal isomer 197 was observed in each applicable case and the product was obtained in good yield and with ee values higher than 90% (Scheme

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• catalyst CpRu(MeCN)3PF6 with a chiral ligand would constitute a much simpler solution to the development of an asymmetric redox bicycloisomerization reaction. To compare the efficiency of each catalyst system, we decided to run the reaction for a shorter period of time, stop the reaction, and check the

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

• metal-catalyzed synthesis The chiral ligand/metal complexes have been widely employed in catalytic asymmetric synthesis of enantioenriched 3-hydroxyoxindoles, achieving good to excellent enantioselectivities and high yields. Pd-catalyzed allylation of isatins The palladium catalyst is widely used in

• regioselectivities and enantioselectivities (up to 98% ee, Scheme 7) [24]. The reactions were performed in 1,2-dimethoxyethane using 5 mol % of [Ir(cod)2](BArF4) as the catalyst and 5.5 mol % of the chiral ligand L4. A wide range of aromatic and aliphatic α-ketoamides were tolerated under the optimized conditions. A

• alkoxide species C. Reductive elimination of species C gave the product and regenerated the active iridium catalyst. Recently, Qiu and co-workers developed a novel chiral ligand L5 based on a chiral-bridged biphenyl backbone and successfully achieved the asymmetric addition of arylboronic acids to N

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• reagents, also used as solvent, were cyclopentane, cyclohexane and cycloheptane. Two factors are noteworthy in this work. Unlike the carboxamide complexes (R)-18 and (S)-18 previously reported by Doyle and coworkers (Table 2), where the complexation of the chiral ligand to rhodium atoms occurs through the

• attributed to high steric demand required by the chiral ligand in the transition state of the carbenoid insertion step in the C(sp3)–H bond. Cyclic alkanes were also tested with yields ranging from 64–80% and enantioselectivities between 88 and 92% ee. The reaction with cyclohexane was conducted on a gram

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• of the lithiated N-Boc-N’-alkylpiperazines with sec-BuLi and TMEDA at −78 °C, the reaction was warmed up to −30 °C with addition of a chiral ligand. The chiral ligand coordinates with the racemic lithiation product to give a diastereomeric mixture which can be resolved under thermodynamic or kinetic

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• provides efficient access to these scaffolds. In particular, exceptional progress has been made in the addition of chiral metal acetylides. Historically, these reactions required stoichiometric amounts of both metal and chiral ligand [8], but catalytic variants are now available with a variety of metal

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• additives such as 4-(N,N-dimethylamino)pyridine caused an unexpected inversion of enantioselectivity in the Cu-catalyzed asymmetric desymmetrization of α,α-bis(2-iodobenzyl)glycines when (2S,3aS,7aS)-octahydro-1H­indole-2-carboxylic acid was used as chiral ligand [47] (Scheme 18). In 2015, Cai et al

• chelating ligands and thus compete with the chiral ligand for binding with the copper salts. Therefore the authors used a mono-aryl halide-substituted malonamide in the presence of a chiral CuI/1,2-diamine catalyst system and obtained the desired products in good yields and moderate enantioselectivities [48

• ]. Oestreich et al. [77] reported the first example of an enantio- and regioselective allylic substitution of linear allylic chlorides and phosphates catalyzed by a Cu/NHC chiral ligand (Scheme 31). Hayashi et al. [78] described a Cu/NHC-catalyzed asymmetric allylic substitution of allyl phosphates with

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• regiocontrol of the nucleophilic attack, which can occur at three different positions, at least. The regioselectivity outcome of the ACA reaction depends on many parameters, notably the metal/chiral ligand combination, the structure of the electrophile and the nature of the nucleophile. Figure 1 depicts the

• system, a combination of Josiphos L9 as chiral ligand and copper thiophene 2-carboxylate (CuTC) afforded the desired 1,6-adducts 43 with very good regioselectivity (up to 5/95) and enantioselectivities (up to 91% ee). Enantioselective 1,4-addition to extended Michael acceptors With dialkylzinc reagents

• could also attain a perfect 1,4-regioselectivity in the addition of trialkylaluminium reagents. Many nitroenynes such as 75 could then be converted to a wide variety of enantioenriched products 76 (83 to 95% ee) using copper thiophenecarboxylate (CuTC) as the copper source and Josiphos L9 as chiral

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• source (Scheme 25). On the other hand, Du and Jia [72] developed a route for the asymmetric chlorination of similar carbonyl substrates 80 via copper-catalyzed asymmetrical α-chlorination in the presence of a chiral ligand. The yield of all products 81 was excellent, and the enantioselectivity, however

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

• ruthenium complex 11 which contain (1R,2R)- or (1S,2S)-N-tosyl-1,2-cyclohexanediamine as chiral ligand (Figure 2). The reaction was carried out in acetonitrile using an azeotropic mixture of formic acid/triethylamine as hydrogen source with 50:1 substrate to catalyst ratio. Under these conditions the

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• to excellent yields and enantioselectivities. In 2006, Pineschi and co-workers reported the copper-catalyzed asymmetric 1,4-addition of alkylzinc reagents to acyclic α,β-unsaturated imides [95]. In this case, the authors used a phosphoramidite as the chiral ligand. They were also able to obtain the

•  14 highlights an example of the rhodium-catalyzed asymmetric 1,4-addition of amides. In seminal reports for the rhodium-catalyzed ECA reactions, BINAP or a BINAP derivative was used as the chiral ligand for these reactions. Hayashi in 2003 [146] and Carreira in 2004 [147] demonstrated that chiral

• previously referenced examples, (S)-Binap has also been used in the 1,4-addition of aryltrialkoxysilanes to a series of α,β-unsaturated amides [154]. In 2005, Hayashi and co-workers developed conditions for the 1,4-arylation of various Weinreb amides, which utilized (S,S)-75 as the chiral ligand [130]. Xu

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• . A DFT study of the hydrolysis in BIFOP–Cl verifies a higher repulsive interaction to water and a decreased leaving tendency of the chloride nucleofuge, which is caused by the fenchane units. This high stability of BIFOP–Cl against nucleophiles supports its application as a chiral ligand, for example

• application as a chiral ligand to be used in, for example, Pd catalysis [13][14][15]. Experimental All reactions were carried out under an inert argon atmosphere and in heated glassware using standard Schlenk techniques. Anhydrous solvents were obtained by distillation from sodium benzophenone ketyl. The NMR

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• (OTf)2/chiral ligand 217/MnO2 system (Scheme 45) [202]. Apparently, product 218 is generated via an ionic mechanism involving the generation of electrophilic nitrosocarbonyl intermediate 219 [202]. The improved version of that oxidative coupling method is based on CuCl/Cu(OAc)2/ligand/air catalytic

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• is attached either to the carbamate or amide (Figure 5) [69][70][71] (using a platinum anode and tungsten cathode electrochemical set-up) [69] or the use of Cu-PyBox chiral ligand systems [72]. The cation pool method can be adapted to a multicomponent reaction (MCR) when an N-acyliminium ion is

P(O)R₂-directed Pd-catalyzed C–H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands

• Rong-Bin Hu,
• Hong-Li Wang,
• Hong-Yu Zhang,
• Heng Zhang,
• Yan-Na Ma and
• Shang-dong Yang

Beilstein J. Org. Chem. 2014, 10, 2071–2076, doi:10.3762/bjoc.10.215

• reported operation, the substrates of biaryl derivatives that contained phosphate with axial chirality were obtained in high yields using the Suzuki–Miyaura coupling reaction with the assistance of this versatile chiral ligand [31][32][33][34]. We used substituted naphthylboronic acid or ortho-substituted

• were successfully synthesized using the Suzuki–Miyaura coupling reaction under the assistance of a chiral ligand. Moreover, the substrates were further C–H functionalized using the P(O)Ar2 directing role with Pd salt as catalyst. Notably, the reactions took place in air atmosphere and at high

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

• ring. As a result, the (R)-enantiomer of the product was predominantly formed, albeit with moderate enantioselectivity. Analogously, in the intermediate I5 derived from chiral ligand L2, the less bulky pseudo-axial phenyl substituent at phosphorus blocks the re-face approach even less efficiently

• ]. Intermolecular asymmetric Heck reaction by Hayashi [16]. Mechanistic rationale of asymmetric Heck reaction. Synthetic scheme for preparation of PHOX ligands with chiral cyclopropyl backbone. Conformational equilibrium in cationic arylpalladium(II) complexes with chiral ligand L1. For discussion on asymmetric

• induction imparted by chiral ligands L1 and L2 (originally published in [64]). For discussion on asymmetric induction imparted by chiral ligands L3 (originally published in [64]). Conformational equilibrium in cationic arylpalladium(II) complexes with chiral ligand L4. For discussion on asymmetric induction

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• ECD data are given as the Δε' values, which are calculated in the usual manner by means of the equation Δε' = ΔA/c × d, A being the absorption, c the molar concentration of the chiral ligand, assuming 100% complexation, and d the path length of the cell. The numbering of the atoms in sucrose dimers is

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• -coupling of benzyl or alkyl halides with racemic secondary phosphines have been developed. These reactions were catalyzed by chiral platinum or ruthenium complexes. The enantioselectivity is based on a dynamic kinetic resolution. Upon reaction with the catalyst precursor containing a chiral ligand (L*), a

• electronegative fluorine atom is needed for the SNAr reaction to take place, even though the arenechromium complexes are already very electron-deficient aromatic compounds. The same group also developed a P-chiral ligand, QuinoxP 74, via deprotonation of chiral secondary phosphine borane 13d with n-butyllithium

• )-BINAP 116; a successful chiral ligand. Nickel was chosen as catalyst instead of palladium to minimize catalyst poisoning by binding of the metal with the phosphines present. After optimization, the desired chiral BINAP 116 was obtained in 77% yield. This protocol has been adopted by other research

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• a one-pot, cycloaddition/allylboration sequence [43][44]. With (S,S)-Norphos as chiral ligand, the desired alcohol 10 was isolated in 87% yield and 71% ee (Scheme 9). In a related process, the same group reported a two-step reaction cascade interconnecting four components to afford dihydroaromatic

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• osmium and chiral ligand contents were varied in the first instance. While the commercial AD-mixes were used, we also carried out the dihydroxylations with 1 mol % osmium/5 mol % ligand, the so-called “improved procedure”, and with 1 mol % osmium/10 mol % ligand (results summarised in Table 1). Methyl

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• (R)-diphenyl(1-methylpyrrolidin-2-yl)methanol (50, (R)-DPMPM) [75] in toluene at 0 °C gave adducts 49 and 16 in a 4:1 ratio (anti/syn). By changing the chiral ligand to (S)-DPMPM 51 the selectivity dropped to 2:1 (anti/syn). When the addition reaction was performed in the presence of achiral N,N

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

• efficient in asymmetric catalysis [23][24]. The high amount of gold per mole of catalyst and the chiral ligand itself make these processes somehow expensive. The relative lower cost of chiral privileged ligand Binap (versus Cy-Segphos) and the good results obtained in the 1,3-DC of α-imino esters and