Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• enantioselectivity, the review will be organized according to these strategies. Mechanistic understanding is vital to furthering development of any field of organic chemistry, so the mechanisms proposed by the authors are included for many examples, although the level of mechanistic investigation that accompanies

• chemical yield and enantioselectivity (all values converted to nearest per cent enantiomeric ratio (er) for clarity) will be the common data for comparison; however, where possible the quantum yields of the photochemical reactions will also be provided as this latter metric provides the most accurate

• catalyst and intermediate 112 for the synthesis of (–)-cephalimysin A in moderate yield and excellent enantioselectivity (98:2 er). Interestingly, there have been multiple reports of racemic reactions that combine photoredox and NHC catalysis [53][54][55][56], but few enantioselective examples, suggesting

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

• solvent dependence of the stereochemical induction of the Diels–Alder reaction by the phenylethyl-derived ligand 2 was studied using N-benzylmaleimide (8e) as dienophile (Table 1). The solvents dioxane (17% ee) and acetone (14% ee) showed a slight decrease of the enantioselectivity compared to THF (21% ee

• ). The yields of the reactions were rather moderate. On the other hand, the use of acetonitrile had no significant influence on the yield compared to acetone while the enantioselectivity dramatically dropped to 8% ee. In this case the lower selectivity correlated with the increasing lithium solvating

• ] is present. Expanding the aromatic unit to a naphthyl group in 3-H2 resulted in an increase of the enantioselectivity to 44% ee. Even better selectivities were obtained with 4-H2 bearing an indanyl [33][34] substituent which combines a stereogenic center implemented in a ring system providing

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• conjugated nitroolefins in the presence of a chiral Ni(II) complex to give nitro keto phosphonates with two stereocenters with excellent enantioselectivity and moderate to high diastereoselectivity. These products were used for a reductive cyclization leading to pyrrolidin-3-ylphosphonic acid and for

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• catalyst. Of the asymmetric strategies, Jacobsen’s and Ghosh’s routes proceeded with the highest enantioselectivity; the catalyst loading was lower for the Jacobsen route (0.5 mol %) compared to the Ghosh route (20 mol %). Synthesis of the (all-cis)-2,3,4,5-tetrasubstituted tetrahydropyran fragment

• in a high yield and enantioselectivity (Scheme 5) [17][18]. The Rubottom oxidation [28] of 43 gave a separable mixture of the desired 44 and its C-14 epimer (≈7:1 ratio). The reductive deoxygenation of 44 proceeded via the tosylhydrazone to afford 45, which upon desilylation and alkyne isomerization

• yield and high enantioselectivity (Scheme 7) [15][16]. The Achmatowicz oxidation and ionic reduction generated the enone 58, which is regioisomeric with 53. The 1,4-addition of lithium dimethylcopper gave the desired cis-55 with high a diastereoselectivity (25:1). The cross-metathesis of 55 with 3

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• similarly to 8a were obtained from benzylamine and tert-butyl isocyanide by varying either acid or 2-oxo-aldehyde components revealed that it was difficult to achieve high enantioselectivity for such substrates. Specifically, none of the studied chiral promoters could afford the desired products 12b and 12c

• with the ee value consistently higher than 50%. Turning to the substrates 8d–g derived from aromatic amines we were able to achieve improved enantioselectivity. The best results were obtained with Q-Bn, DHQ-Bn, DHQD, and QD-Bn that performed consistently well with each of the substrates 8d–g delivering

• . Testing Ugi adduct 8h allowed us to highlight the possibility of simultaneous variation of acid, 2-oxo-aldehyde, and amine components. Overall, four cinchona derivatives were screened with 8h producing the fluorinated product 12h with moderate to good enantioselectivity, which was consistent with the

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• catalyst effectively catalyzed Biginelli-like reactions with moderate to good enantioselectivities. Control experiments indicated that the presence of the two hydroxy groups were indispensable for achieving a high enantioselectivity. Keywords: asymmetric Biginelli-like reaction; chiral 1,1,4,4

• compound making its application highly attractive from the viewpoint of sustainability and green chemistry. Recently, our group reported an asymmetric Biginelli reaction catalyzed by a new chiral phosphoric acid derived from natural tartaric acid, that yielded a high enantioselectivity (up to 99% ee) [17

• solvent screening showed that the target product could be obtained in 95% ee catalyzed by 3 in CHCl3 (Table 1, entry 4). However, acidic and basic additives [23][24] resulted in a decrease of the enantioselectivity (Table 1, entries 10–12), or even to racemization in the case of TFA (Table 1, entry 13

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• specifically the Hashimoto catalyst ([Rh2(S-TCPTTL)4]) was found to be the most efficient in terms of yield and enantioselectivity. In this study, the authors described an example of an intermolecular PKR using the strained difluoromethylated cyclopropene 73 which, upon reaction with the hexacarbonyldicobalt

• complex prepared by treatment of the 1-butyne with Co2(CO)8, afforded the corresponding bicyclic cyclopropane-fused cyclopentenone 74 in high yield and high enantioselectivity (Scheme 43). Conclusion In conclusion, as highlighted in this review, the PKR is still a hot area of chemical research as it

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• -aroyloxyaldehydes and trifluoroacetophenones, followed by ring opening with an amine or a reducing agent is described. The resulting β-trifluoromethyl-β-hydroxyamide and alcohol products are produced with reasonable diastereocontrol (typically ≈70:30 dr) and excellent enantioselectivity, and they can be isolated in

• -substituted β-lactone products in a high yield, diastereo-, and enantioselectivity (Figure 2A) [46]. Chi and co-workers have reported limited examples of oxidative [2 + 2] cycloadditions using hydrocinnamaldehyde as an azolium enolate precursor and the NHC precatalyst 2, giving β-lactone products in high

• enantioselectivity but requiring superstoichiometric quantities of quinone as an oxidant (Figure 2B) [47]. In our previous work, we have developed α-aroyloxyaldehydes as reactive, bench-stable precursors of azolium enolates [48][49][50][51][52][53], which can be synthesized in a single step from the desired aldehyde

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• engage with the peptide backbone via an H-bonding interaction, and in order to achieve a high enantioselectivity, the amide functionalization of the peptide at the 4-proline position is essential. Amide-substituted vinylcyclopropanes have a relatively good H-bond-donating ability, so they are more

• successful substrates for this transformation. Although multiple olefins can be successful olefinic coupling partners for this reaction, electron-rich olefins bearing an α-heteroatom would be preferable for achieving a better enantioselectivity. In 1990, Singleton and co-workers reported disulfide-catalyzed

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

• enantioselective methods for the synthesis of these compounds resulting in high yield and enantioselectivity has proven challenging. As a result, significant effort has been invested into copper-catalysed asymmetric conjugate addition reactions using organometallics. In 2005, Feringa and co-workers reported on the

• efficient one to achieve an enantioselectivity of up to 96% ee. Interestingly, piperidones with different carbamate protecting groups (Me, Et, Ph, tosyl, and Bn, respectively) were tolerated, and a high enantioselectivity could also be obtained with several other dialkylzinc reagents (e.g., iPr2Zn and n

• -Bu2Zn, respectively). Later, T. Shibata and K. Endo prepared the same product (2c) with a higher enantioselectivity (97% ee) by using the multinuclear phosphorus ligand catalyst L2 [16]. Organoaluminium reagents are also commonly used organometallics in copper-catalysed ACA reactions. For example, in

Pd-catalyzed asymmetric Suzuki–Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position

• Yongsu Li,
• Bendu Pan,
• Xuefeng He,
• Wang Xia,
• Yaqi Zhang,
• Hao Liang,
• Chitreddy V. Subba Reddy,
• Rihui Cao and
• Liqin Qiu

Beilstein J. Org. Chem. 2020, 16, 966–973, doi:10.3762/bjoc.16.85

• enantioselectivities (up to 88% ee) under mild conditions. The chiral-bridged biphenyl monophosphine ligands developed by our group exhibit significant superiority to the naphthyl counterpart MOP in both reactivity and enantioselectivity control. The large steric hindrance from π-conjugated ortho-substituents of the

• bromobenzene substrates and the Pd···O interaction between carbonyl and palladium seem essential to achieve high enantioselectivity. Keywords: asymmetric catalysis; biaryls; monophosphine ligand; palladium catalyst; Suzuki–Miyaura couplings; Introduction Axially chiral molecules have received much attention

• ], especially on how to obtain the large steric axially chiral biaryl with a high yield and good enantioselectivity through those coupling strategies [13]. Therefore, based on our previous research [60][61][62][63][64][65], we herein present a new method through which those large steric axially chiral biaryl

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• ). Acetonitrile gave the highest yield (55%) and ee (72%) of product (S)-11 in presence of Λ-10 as catalyst. While the free ligand is found to catalyze the reaction, the authors show that the templating effect of the copper ion is necessary to sustain enantioselectivity. Himmel and co-workers have reported the

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• constructing the five-membered oxacyclic ring. As stated in this protocol, a functionalized enyne precursor was prepared in several steps with high enantioselectivity (92% ee), starting from isovanillin. This precursor underwent a ring-closing metathesis in the presence of the Grubbs first-generation Ru

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• PhMe2Si moiety in a 1,4-manner to unsaturated nitro and cyano derivatives leading to adducts 209–218, each being obtained in high chemical yield and good enantioselectivity (Scheme 37). 1.5 Miscellaneous reactions The Tsuji group developed a mild method for the regio-divergent silacarboxylation of allenes

• enantioselectivities remain unaffected. In addition to the impact of steric effects, variations in the alkyl-substituted silicon reagents also negatively impacted the chemical yields. However, again, there was no effect on enantioselectivity. Interestingly, upon replacement of the alkyl groups on the silicon by three

• )- and (E)-alkenes 311 afforded the (E)-alkene 312 as the major product. The targeted γ-borylated compounds (relative to the leaving group) were formed, each with high enantioselectivity, which can be used for further stereoselective C–C and C–X (X = heteroatom) bond formation. Catalytic Cu(NHC)-mediated

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• no enantioselectivity at all. As arylboronic acids have been harnessed to enhance the Brønsted acidity in asymmetric organocatalysis in combination with chiral diols or chiral aminoalcohols [40][41][42][43][44], we envisioned that the simultaneous use of arylboronic acids and chiral Brønsted acids

• the chiral additive in combination with 2-carboxyphenylboronic acid (COOH-BA) in the model reaction (Table 1, entries 3–8). We were pleased to find that CDSI-4 gave the most promising result in terms of both yield and enantioselectivity (64% isolated yield with 73% ee, Table 1, entry 6). An

• to further improve the enantioselectivity promoted us to search for other practical solutions. Considering the poor solubility of 4a in organic solvents, a dissolution–filtration process with isopropanol was found to be workable for increasing the final ee value. This simple procedure could afford 4a

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

• diethoxymethylsilane (4 equiv) as a reductant and t-AmOH (1 equiv) as a protonation reagent in DMA as the solvent at 25 °C for 15 h, the product 2a was produced in 98% yield (1H NMR analysis) with a promising enantioselectivity of 69% ee (Table 1, entry 1). When the phenolic hydroxy group of L1 was changed to a

• methoxy group (in L2), the enantioselectivity drastically dropped to −10% ee, while the yield remained 99% (Table 1, entry 2). Similarly, N,N'-dimesityl-NHC L3, which lacked an oxygen functionality in the N-aryl group, showed poor enantioselectivity (9% ee) with high yield (99% yield, Table 1, entry 3

• ). Thus, the hydroxy group of L1 was essential for the enantioselectivity by the catalyst. When the mesityl group of L1 was changed to a bulkier 2-Me-4,6-Cy2-C6H2 group in L4, the enantioselectivity was markedly improved to 90% ee, with a high yield (97%, Table 1, entry 4). A naphthol substituent on the

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• catalysis [116]. However, the majority of them exhibited good to moderate enantioselectivity. The syntheses of chiral phosphinooxazolines was reported independently by Williams et al., Pfaltz and Helmchen, and Matt and Pfaltz [48][116][117]. Pfaltz et al. reported on the postfunctionalization in the

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

• reagents to these challenging Michael acceptors, with excellent regio- and enantioselectivity. Furthermore, thanks to their easy derivatization, the resulting chiral conjugated products could be converted into various natural products. The aim of this tutorial review is to summarize recent advances

• moderate to good yields, with ee values of up to 76%. When the conjugate addition was performed with Grignard reagents, significant amounts of 1,2-products and enols were formed, despite the use of cryogenic conditions. (R)-BINAP (L2) gave the best regio- and enantioselectivity, with 62% of the 1,4-product

• combination with (R)-TolBINAP (L3), a promising 85% regioselectivity was observed, without altering the enantioselectivity (90% ee), whereas only 32% of the desired 1,4- product was obtained without TMSCl [20]. With those optimized conditions, various enals and Grignard reagents were screened. Nevertheless

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• Bratislava, Mlynská dolina, Ilkovičova 6, 84215 Bratislava, Slovakia 10.3762/bjoc.15.290 Abstract A range of chiral hydrogen-bond-donating organocatalysts was tested in the Ireland–Claisen rearrangement of silyl ketene acetals. None of these organocatalysts was able to impart any enantioselectivity on the

• diastereoselectivities, and ees up to 86% [26]. Rearrangement of allyl esters of glycine derivatives gave under similar conditions amino acids with a quaternary stereocenter on the β-carbon with high yields and excellent diastereo- as well as enantioselectivity [5]. A reductive rearrangement of allyl esters of acrylic

• activate the enolates or the corresponding silyl ketene acetals or stabilize the corresponding transition states. In addition, chiral organocatalysts could induce diastereo- as well as enantioselectivity. Therefore, we examined the Ireland–Claisen rearrangement of ester 1c in the presence of a range of

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

• . Notably, the highest optical yields were achieved using strychnine (Scheme 8) [31]. Similarly, by applying modified electrolytic conditions, in 1993, Schoo and Schäfer increased the enantioselectivity of the alkaloid-catalyzed enantioselective electroreduction of 4-methylcoumarin (8) relative to that

• of methyl-substituted diols 51 on a TEMPO-modified graphite felt electrode in the presence of the chiral base (−)-sparteine (43) with excellent enantioselectivity (conditions A, Scheme 20) [51]. Later in 2003, they reported another protocol for a graphite felt electrode for asymmetric electrochemical

• supporting electrolyte. A slight improvement in the enantioselectivity (8.4% ee) was observed using 55b [55]. Kodama explained the reason of chiral induction in terms of ion pair interaction [56]. A further improvement in stereoselectivity was reported by Yadav, who added tetrabutylammonium trifluoroborate

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• reduction conditions to afford cyclohexa-1,4-diene 13 [9]. Enantioselective Sharpless dihydroxylation proceeded in good chemoselectivity but with modest yield and optical purity (25% ee). Unfortunately, all attempts to improve the enantioselectivity of this reaction failed. We discovered, however, that at a

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• conditions with excellent enantioselectivity and yields, a broad substrate scope, as well as a wide range of functional group compatibility. Notably, this strategy overcomes the challenges associated with the formation of secondary allylic fluorides bearing α-linear substituents, providing complete regio and

• were thus obtained with good enantioselectivity. In the same year, Kim’s group [97] accomplished an efficient enantioselective electrophilic α-fluorination of various α-chloro-β-ketoesters catalyzed by chiral nickel complexes with good enantioselectivity (up to 99% ee). Notably, the chiral nickel

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• reaction with the highest enantioselectivity. The importance of the bifunctional system for the catalytic activity and enantioselectivity was demonstrated by performing a series of reactions with lower activity and selectivity, utilizing free-base porphyrin 16h with triazolium moieties and the two

• component catalytic system composed of 16c before methylation and TBAI as reference catalysts. Optimization studies of the reaction conditions showed that the addition of CHCl3 and lowering of the reaction temperature (to 10 °C) considerably increased the enantioselectivity (s value of 4.1). An evaluation

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

• )-18 furnished, after in situ reduction, diol (2R,3R)-6 with high syn-diastereo- and enantioselectivity (Scheme 6). Conclusion We have demonstrated that oxygenation of aldehydes with singlet oxygen can be successfully achieved in the presence of diphenylprolinol silyl ether affording diols in a highly

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• ) is one of the benchmark reactions for photoredox catalysis because it combines photoredox catalysis with organocatalysis [53]. Initially, [Ru(bpy)3]Cl2 was applied by MacMillan et al. as photoredox catalyst together with the chiral imidazolidinone 15 as organocatalyst to achieve enantioselectivity

• following paragraphs because enantioselectivity is not a matter of discussion in this work. The photoredox catalysis with NDI 1 was performed by LEDs with 387 nm maximum emission wavelength and an irradiation time of 18 h. In order to ensure solubility of all components, a solvent mixture of DMF/CH2Cl2 = 1