Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• great attention in organic synthesis. Various methods [9], including reductive hydrogenation [10][11], kinetic resolution [12][13][14], functionalization of indole [15], and de novo construction of chiral 2-substituted indolines, have been developed [16][17][18][19][20]. In recent years, the metal

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• chirality which exhibits no racemization under action of strong bases [29]. The chiral N–H-containing rimantadine-based ligand (L6) is highly lipophilic and it was successfully used for the kinetic resolution of unprotected racemic amino acids [30]. The examples mentioned above show that the metal–Schiff

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• acetal group could be used as substrates in an aza-Nazarov cyclization with the intermediacy of in situ-generated N-acyliminium ions (Scheme 1b) [21]. The first catalytic aza-Nazarov reaction was reported by Tius and co-workers in 2010, which involved the kinetic resolution of azirine derivatives via an

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• kinetic resolution of racemic alcohols [99] and for the oxidation of benzylic cyclic ethers to lactones [100] was demonstrated. The CuI/9-azabicyclo[3.3.1]nonane N-oxyl (ABNO) catalytic system successfully promotes the oxidative coupling of alcohols with primary amines [101] (Scheme 13). The reaction

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• the unsymmetrical salens with zinc, copper, and cobalt was studied and the chiral Co–salen complex 2f was obtained in 98% yield. Hydrolytic kinetic resolution (HKR) of epichlorohydrin with water catalyzed by complex 2f (0.5 mol %) was explored and resulted in 98% ee, suggesting complex 2f could serve

• with regard to conformational differences, for instance, oligosalen [14], macrocyclic oligosalen [15], and polymeric salen [16]. Jacobsen and co-workers reported the first synthesis of α-aryloxy alcohols through the phenolic kinetic resolution (KR) of terminal epoxides using a Co–salen catalyst [17

• were explored as well. Furthermore, we present the hydrolytic kinetic resolution (HKR) of epichlorohydrin with water using Co–salen complexes 2, and α-aryloxy alcohols were synthesized by the 2f catalytic system through the asymmetric ring opening of epichlorohydrin and phenols. Results and Discussion

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• stereoselective kinetic resolution of allenol 3 via lipase AK-catalyzed acetylation [15]. In this way, unaltered, (−)-hydroxyallene 3 could be separated from (+)-acetyl derivative 9 through standard column chromatography (Scheme 3). Enantiomeric excesses of (−)-3 and (+)-9 were determined by chiral HPLC analyses

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• material were practically the same as the one of the starting material in all cases. Further, the separation via kinetic resolution in the final reaction step was also examined. The course of the re-esterification was stopped at a conversion of ca 50% and the de values were determined. Unfortunately, no

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• Waser employed an isothiourea catalyst for esterification-mediated kinetic resolution of paracyclophane derivatives with planar chirality [19]. Parida and Pan showed that a Michael reaction coupled with an acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones can produce a

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• degree of variability for the generation of small libraries, in our case of Cyl-1 derivatives. Chiral allylic alcohols are easily accessible, either via kinetic resolution of racemic alcohols [46][47], asymmetric catalysis [48], or from chiral pool materials, such as threitol 1 [49]. Using the last

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• axial chiral compounds has been paid much attention [6], and great progress has been made in recent years. For example, many remarkable activities have been undertaken to develop strategies such as dynamic kinetic resolution, atroposelective coupling, cycloaddition, and chirality conversion for the

• (kinetic resolution) in the presence of chiral phosphoric acid CPA 3. In this work, various EWG- and EDG-containing substrates were incorporated, and chiral biaryls 10 were obtained with good to excellent selectivities of 81–93% ee by desymmetrization and 63–96% ee by kinetic resolution. The subsequent

• asymmetric addition reaction of racemic naphthylindole 42 with azodicarboxylate 43 under chiral phosphoric acid catalysis. In the presence of CPA 2, 42 and 43 reacted and underwent dynamic kinetic resolution to afford naphthylindoles 44 with axial chirality in moderate to good yields (50–98%) and high

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• nucleoside analogues. The enantiomerically pure 1,3-oxathiolane core has been an important building block in precursors that result in a defined stereochemistry of the resultant nucleoside product after N-glycosylation. Dynamic kinetic resolution (DKR) is a processes that interconverts a racemic mixture into

• -oxathiolane with Trichosporon laibachii lipase and a kinetic resolution. The synthesis of enantiopure ((R)-5-acetoxy-1,3-oxathiolan-2-yl)methyl benzoate (71) was carried out from the substrates 3a, 1,4-dithiane-2,5-diol (3q), and phenyl acetate via dynamic covalent kinetic resolution. This was a one-pot

• achieved. In 2014, Zhang et al. [64] reported an optimized asymmetric synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution using hemithioacetal chemistry coupled with a lipase-catalyzed cyclization (Scheme 25). Methyl thioglycolate (3j) was used in the reaction with aldehyde

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• transferred between the oxygen atoms after the alkyl migration, making it especially useful in synthetic strategies using these protected intermediates. Additionally, the reaction was found to be useful in the kinetic resolution of a racemic mixture of chiral substrates possessing both alkyl and aryl α

• . The catalyst is also capable of kinetic resolution of a mixture of enantiomeric substrates. Al* = 18. BF3-promoted diastereospecific rearrangement of α-ketol 21 to difluoroalkoxyborane 22. In the presence of a gold catalyst and water in 1,4-dioxane, 1-alkynylbutanol derivatives undergo tandem

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• maintain due to the conformational lability of the seleniranium ion [52][53][54], this initial problem can be exploited through the addition of an anion-binding catalyst. In this way, the configurational scrambling is used for a dynamic kinetic resolution during the intramolecular nucleophilic opening of

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• David Weinzierl Mario Waser Institute of Organic Chemistry, Johannes Kepler University Linz, Altenbergerstrasse 69, 4040 Linz, Austria 10.3762/bjoc.17.68 Abstract We herein report a method for the kinetic resolution of racemic 4-hydroxy[2.2]paracyclophane by means of a chiral isothiourea

• -catalyzed acylation with isobutyric anhydride. This protocol allows for a reasonable synthetically useful s-factor of 20 and provides a novel entry to obtain this interesting planar chiral motive in an enantioenriched manner. Keywords: acylation; kinetic resolution; nucleophilic catalysis; paracyclophanes

• transformation into diastereomers by esterification with chiral acid chlorides [19][20] as well as the kinetic resolution (KR) of racemic esters of 2 via an enzymatic hydrolysis [25][26][27] were very successfully used to access enantioenriched 2. Recently, Akiyama and co-workers reported the kinetic resolution

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

• ) in the kinetic resolution of primary amines 60 via their electrocatalytic oxidation to the corresponding ketones 62, and remaining amines (R)-60 were obtained with very high enantioselectivity. The controlled potential electrolysis was carried out in a divided cell in the presence of a base and a

• catalytic amount of 61 (Scheme 24) [59]. A similar strategy using N-oxalyl radicals as chiral mediators has also been explored for the enantioselective electrocatalytic oxidation of secondary alcohols [60]. Tanaka and co-workers subsequently published another article on the kinetic resolution of sec

• electrochemical asymmetric oxidation of 1,2-diols 74 and amino alcohols 77 in presence of a Br- mediator using Cu(OTf)2 and (R,R)-Ph-BOX 76 as the catalytic system (Scheme 29). The method enabled an asymmetric synthesis of α-hydroxycycloalkanones 75 and α-amino esters 78 along with the kinetic resolution of

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

• isolated from fungi of the genus Acremonium. Here, we present the asymmetric total synthesis of acremine F which hinges on a modestly enantioselective dihydroxylation and a subsequent kinetic resolution via a highly selective asymmetric reduction. Chemoselective oxidation of acremine F gave access to

• . The use of a chiral oxazaborolidine catalyst led to kinetic resolution and increased the optical purity of 17 to 95% ee. Deprotection of the diol moiety followed by Stille cross coupling with vinyl stannane 18 finally gave 5 in excellent yield (Scheme 2). Since acremine F (5) can be expected to be the

• modestly enantioselective oxidation and a highly enantioselective reduction with kinetic resolution to access the acremine framework. The route proved to be scalable and delivered 300 mg of the natural product. Acremine F could further be converted into acremines A (1) and B (2) by a selective oxidation

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

• kinetic resolution of epoxides with CO2 remains a big challenge. Recently, Ema and co-workers described a chiral binaphthyl strapped Zn(II) porphyrin with triazolium halide units as a bifunctional catalyst for the kinetic resolution of epoxides with CO2 [63]. The condensation of click-reaction-derived

• compound 8. Chemical structures of compound 9. Chemical structures of compound 10, 11 and 12. Chemical structure of compound 13. Chemical structure of compound 15 including the sigma-connected TCNQ dimer. Chemical structure of compound 16 for the kinetic resolution of epoxides. Chemical structure of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• both pairs of ethyl esters [26]. When a mixture of tert-butyl esters (2R,1'S)-5d and (2S,1'S)-5d was subjected to kinetic resolution in the presence of potassium tert-butoxide in tetrahydrofuran (2R,1'S)-5d was produced with low 40% de [27]. The absolute configuration at C2 in esters 5 was established

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• excesses, which result, according to the authors, from a dynamic kinetic resolution of the initially formed Ugi adduct. Indeed, the plausible mechanism for the reaction implies the condensation of amine 2 and aldehyde 33 to form iminium salt intermediate 47 (Scheme 14). Next, addition of isocyanate 42

• rearrangement that would lead to isoindolinone 46 through the bridged intermediate 51. Therefore, this mechanistic path shows that the enantioselectivity of the reaction is a consequence of a dynamic kinetic resolution of enamine 50. Cyanide can also be used, instead of isocyanide, in an analogous three

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• ). However, purification of 4a by column chromatography on SiO2 favored acyl migration in 4a, thereby dropping the yield of 4a by increasing the amount of the isomeric sn-2,3-protected monoacylglycerol 4a’ (Figure 2) [42]. Typically, cobalt complex (S,S)-cat has been used for kinetic resolution of racemic

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• the corresponding secondary cyclopropenylcarbinol (S)-1f (ee = 99%), which in turn is readily available by applying the Sharpless kinetic resolution procedure to (±)-1f [31], was also investigated. The resulting geometric isomers (Z)-3f and (E)-3f, which were separated by flash chromatography, were

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• and characterization of four enantiomers 2 (Figure 3) came from the Japanese sources [45][46][47][48]. For identification purposes (2S*,3R*)-2 and (2S*,3S*)-2 were resolved by chiral reversed-phase TLC [26]. Kinetic resolution of dibenzyl (2S*,3R*)-N-Boc-3-hydroxyglutamate was achieved in the presence

• (Scheme 11) [60]. Sharpless epoxidation of the allylic alcohol 48 gave a 46:11:33 mixture of (S)-48, (3R,4S)-49 and (2R,3R)-50. While (S)-48 is a product of kinetic resolution, the formation of (2R,3R)-50 results from the intramolecular opening of the oxirane ring in (3R,4S)-49. After chromatographic

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• are easily regenerated in situ without the need for another enzyme. In principle, enantiomerically pure chiral amines can be prepared following two approaches: through kinetic resolution starting from racemic amines or by asymmetric synthesis starting from suitable substrates, e.g., the corresponding

• carbonyl compounds. In a kinetic resolution, a maximum yield of 50% of the product can be obtained. Moreover, high quantities of the co-product might complicate the product separation and the recovery of the chiral amine. Thus, the asymmetric synthesis is generally preferable because a theoretically 100

• commercial free form or isolated from bacterial sources, both in kinetic resolution starting from the corresponding racemic amine and in asymmetric synthesis starting from the corresponding ketone. The first method, although it proceeds with high enantioselectivity, is a kinetic resolution and as a

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• , reaction 1) [31]. Kinetic resolution of racemic α-trifluoromethylated tertiary alcohols 2a by an enzyme is also reported to give the corresponding alcohols 2a in high enantioselectivity (Scheme 1, reaction 2) [32]. However, there has been no report for catalytic asymmetric methylation of trifluoropyruvate

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide

• catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er. Keywords: kinetic resolution; Michael addition; organocatalysis; pregabalin; squaramide; Introduction Asymmetric organocatalysis has considerably broadened possibilities for

• ][21]. Other green chemistry concepts such as reusable media [22], immobilized catalysts [23], or flow set-ups have also been used with success for the synthesis of GABA derivatives [24]. Pregabalin is currently manufactured using enzymatic kinetic resolution [25], but an organocatalytic procedure