Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• reported. A bifunctional thiourea catalyst was found to be effective for this reaction. With 10 mol % of the catalyst, good results were attained for a variety of 1,5-dihydro-2H-pyrrol-2-ones under mild reaction conditions. Keywords: acyl transfer; enantioselectivity; Michael reaction; organocatalysis

• be suitable reaction partners of α-nitroketones. However, during the progress of our work, Bonne, Bugaut and co-workers have shown one example for the reaction of 2-nitroacetophenone with 4-benzylidenepyrrolidine-2,3-dione and only moderate enantioselectivity (50% ee) was achieved (Scheme 1) [25

• quinine and cinchonidine-derived bifunctional thiourea catalysts III and IV were employed in the reaction and moderate enantiomeric excesses were achieved. The yield and enantioselectivity further improved when using the tert-leucine-derived thiourea catalyst V. Also, Takemoto’s catalyst VI [28] was

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• often a work-up procedure meaning that this approach is very accommodating of direct telescoping into further reaction steps and reactors. So far, heterogeneous catalysis of aldol reactions in flow has been mostly geared towards achieving transformations with high enantioselectivity, towards decreasing

• , the (S)-enantioselectivity could be reversed by inversion of stereochemistry at the terminal proline moiety of the supported peptide. Ötvös’ protocol highlights some of the key advantages of this immobilisation approach, i.e., improved reaction kinetics over batch (higher effective catalyst loading

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• in excellent yields (89–94%) and enantioselectivities (95–99% ee; Table 3). It is worth mentioning that a free phenolic hydroxy group did not interfere with the Pd complex and did not affect the enantioselectivity of the reaction. The authors also demonstrated that the product mixture obtained after

• combination provided the product in an excellent yield (60–99%) and enantioselectivity (up to 97% ee; Table 4), the only exception being the addition of an ortho-substituted boronic acid (entry 5, Table 4) [36]. In 2008, the same group further expanded the substrate scope of the addition reaction to electron

• -hydride elimination. However, the obtained yields were inconsistent. The usage of Pd(TFA)2 led to a better reproducibility of the results. From the various diphosphine ligands tested, (R,R)-MeDuPhos (L2) was identified as the one leading to the best level of enantioselectivity (up to 99% yield and up to

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• hydroxyallylsilane 186 with excellent enantioselectivity (Scheme 45) [83][84][85]. This, upon further reaction with another aldehyde in the presence of TMSOTf, gave 2,6-disubstituted 4-methylenetetrahydropyran 187. This strategy was utilized for the synthesis of bryostatin and (+)-dactyloide analogs [86][87][88

• enantioselectivity varied with the polarity of the solvent. The optimization study disclosed that the enantioselectivity increases with the decrease of the polarity of the solvent (Scheme 68). Yu and co-workers reported a novel segment-coupling Prins cyclization involving sequential benzylic/allylic C–H bond

• with alcohol 307 to obtain 309 (Scheme 71) [113]. The introduction of electron-withdrawing nitro groups on the BINOL backbone in the catalysts significantly enhanced the reactivity and enantioselectivity. Zhou et al. reported an asymmetric Prins cyclization of in situ-generated quinone methides from

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• ] showed how these changes reflected an unchanging characteristic of the enzyme, the enantioselectivity E, equal to the ratio of kcat/Km values for the two enantiomers. The Chen and Sih equations are widely used to analyse the progress of resolution reactions. Chen and Sih also described the influence of

• are labelled by “SC”, usually followed by R or S (for the two enantiomers), then f or b to indicate the forward or backwards progress through the relevant two steps. SC values were normally used for the two steps that involve enantioselectivity (2 and 3 for the ordered, second mechanism, 3 and 4 for

• enantioselectivity in resolution reactions. Similarly, the ratio SCRf/SCRb was found to have an important influence in all cases – it is given the symbol SCRf/b. For the ping-pong, both mechanism, the ratio SCR2f/SCS2f is also relevant, and was given the symbol E2. Behaviour for “ordered, second” kinetics This is

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• same time providing effective asymmetric induction in the capture of the resulting radical along with enantioselectivity of the product. In 2016, based on the experimental work in 2015 [27], Yu and colleagues [29] reported a type of EDA complex that could complete the hydrotrifluoromethylation of

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• reported. The sequence starts with a new tandem nucleophilic substitution/Brook rearrangement/single electron transfer-induced radical oxygenation furnishing orthogonally protected α,γ-dioxygenated N-allylamides with wide scope, mostly good yields, and partly good diastereo- and enantioselectivity for

• represents an oxidative C–C/C–O difunctionalization at the α-position of the amides. With correct configuration combination of chiral epoxides 7 and chiral amides 8, 2,4-dioxygenated amides 9 can be obtained with good anti-diastereoselectivity and enantioselectivity. Dioxygenated amides 9 are convenient

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• and thiourea–quinine organocatalysts both gave the target compound with only 41% ee, which was well below satisfactory (Table 1, entries 10 and 11). The best catalyst in terms of enantioselectivity proved to be the newly designed catalyst 5, which gave the desired product with 63% ee in 1 hour (Table

•  1, entry 1). After selecting the best-working catalyst, optimization studies were initiated on the model reaction to determine the conditions to achieve the best enantioselectivity. The first parameter screened was the effect of the solvent. Using THF and dioxane (Table 1, entries 14 and 16

• values. Thus, THF was selected as the best solvent despite the longer reaction duration. Then, the catalyst loading was varied between 0.1 and 10 mol % to investigate its effect on the enantioselectivity (Table 2, entries 1–6). At an extremely low catalyst loading of 0.1 mol %, the reaction was too

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• )-monoacetate (S)-80, respectively (Scheme 32). As for the transesterification, a high yield (96.5%) and enantioselectivity (91.3% ee) were obtained using lipase PS in benzene. In the case of the deacetylation, the use of Amano PS lipase in acetone gave a high yield (86.2%), enantioselectivity (91.7% ee), and

• nitrile hydratase–amidase-containing biocatalytic system and showed a high chemo-, regio-, and enantioselectivity in the hydrolysis of nitriles and dinitriles. The biocatalytic transformations of nitrile 81 (Scheme 33) supplied an effective route to optically active 2,2-difluorosubstituted 3

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• trans product. Thus, the proper choice of the gold catalyst allows highly stereoselective formation of either cis or trans cyclopropanation products and facilitates the isolation of pure isomers. Despite the chiral nature of these ligands, no enantioselectivity was observed in the test reactions

• . A high catalytic ability was shown for novel N,N,N,N-Au(III) complexes 5a and 6a in alkyne carboalkoxylation and propargyl ester cyclopropanation (full conversion in 1–24 h, 62–97% product yields). No enantioselectivity was observed in the test reactions. The activity and stability of the Au(III

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• system. Based on the above-mentioned approaches, organic and inorganic template-assisted diverse supramolecular assemblies have been constructed to optimize the photochemical reactivity as well as regio- and enantioselectivity [5][6]. In addition, to understand the excited-state properties of the guest

• external factors of this photocyclodimerization reaction (such as the temperature, pressure, salt concentration, and host substituents), the regio- and enantioselectivity could considerably be varied to 71% ee for 14 and 45% ee for 15, respectively. In this supramolecular system, the 2:2 complex could

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• exhibited complexation constants higher than the butyl-substituted analogues 7b and 8b for all anions – compare 7a (Table 1, run 5, K = 660 M−1) vs 7b (Table 2, run 15, K = 90 M−1). On the other hand, despite the differences in the K values, the enantioselectivity remained almost the same in both receptor

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