Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• Diels–Alder reaction [21][22] and (2) a chiral ligand 2-H2 for the stereocontrol [13]. Cleaving the complex under acidic conditions resulted in the desired enantiomerically enriched product 9 and enabled the recovery of the chiral ligand 2-H2 (Scheme 2) [13]. The solvent choice allowed on/off-switching

• auxiliary, Lewis acid or catalyst. In the previously reported system two different induction pathways were conceivable: (1) A chiral ligand is located close to the diene and controls the stereochemistry of the cycloaddition. (2) The chiral ligand controls the helicity of the helicate (ΔΔ or ΛΛ) and the

• reaction yielded the racemic product after purification. Scheme 3 is showing that the induction of stereochemistry of the Diels–Alder reaction depends on the chirality at the chiral ligand and not at the helix. This allows improvement of the stereoselectivity by using more appropriate sterically hindered

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• the total synthesis of the natural product (+)-myrtine with 14% overall yield (Scheme 1B) [17]. For this application, the highest yield (73%) and enantioselectivity (96% ee) were obtained using the chiral ligand L3 and a copper salt as the catalyst. Despite the fact that examples of high yield and

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• systems, while the observation of a higher enantioselectivity for the (Z)-isomer substrate 1a was characteristic for the phenol–NHC chiral ligand [4][6][8]. The result suggested that the chiral catalyst may mainly discriminate the hydrogen atom and the ethoxycarbonyl group at the α-position rather than

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• , and triorganoaluminium reagents to α,β-unsaturated aldehydes (Scheme 5). With diethyl- and dimethylzinc, and in the presence of the most efficient chiral ligand (R)-H8-BINAP (L7), moderate to excellent regioselectivities (1,4:1,2 ratios up to 100:0) were observed, and the desired 1,4-products were

• enantiomers of the chiral ligand, either anti- or syn-1,3-deoxypropionate units were produced in good yields and excellent enantioselectivities (85–92% ee). Furthermore, an iterative procedure was also performed leading to all-syn or anti/syn-5,7,9-stereotriads, with high yields and stereoselectivity. This

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• ). Constant current electrolysis of 89 in a single compartment cell using a sacrificial Mg anode was conducted in the presence of a Ni catalyst and chiral ligand 90. After esterification and purification, 91 was isolated in a good yield and with moderate enantioselectivity [70]. In another recent report, Guo

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• the presence of commercially available inexpensive salts (AgOTf, AgNO3) and eventually a (chiral) ligand. Such silver(I) complexes were prepared by using (bi)pyridine [19][23][24][25][26], phosphine [22][27][28][29][30], ditopic N/P [22] ligands and a few S/P and S/N ones [31][32][33][34]. None of the

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• ’ = ΔA/c × d, where c is the molar concentration of the chiral ligand, assuming 100% complexation (A = absorption; d = path length of the cell). Δε’ is expressed in [M−1 cm−1] units. Conformational analysis and ECD calculations The conformational search was performed with ComputeVOA [35] using the MMFF94

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• ]. In this case, the ZnMe2-mediated reaction employed N-methylephedrine as chiral ligand which provided the corresponding chiral β-amino esters with enantioselectivities of up to 94% ee. Later in 2008, Feringa introduced the first catalytic enantioselective version of the Reformatsky reaction involving

• aldehydes as electrophiles [38]. Enantioselectivities of up to 84% ee were achieved by using a BINOL derivative as chiral ligand. Ever since, other types of chiral ligands including chiral Schiff bases [39], bisoxazolidines [40], 1,2-amino alcohols [41], indolinylmethanols [42], and diarylprolinols have

• in this process was essential for the effective C−C bond formation. They proposed the catalytic cycle depicted in Scheme 20 which begins with the reaction between chiral ligand 51, ZnEt2 and ethyl bromoacetate (9b) to give complex G. Addition of the aldehyde to the latter results in the formation of

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