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

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• diameter) [9], demonstrated to efficiently mediate the enzymatic kinetic resolution of secondary alcohols under solvent-free conditions in both mixer and planetary ball mills (Scheme 1b) [10]. Interestingly, this latter lipase (a commercial preparation known as Novozyme 345, hereinafter referred as CALB

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• conditions (for selected other uses of oxaziridines in asymmetric α-hydroxylation reactions please see [123][124]). Interestingly, this transformation is accompanied by a kinetic resolution of the employed oxaziridine with s-factors up to 45 [116]. One potentially useful simple reagent to carry out oxygen

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• ][18][19][20][21][22] including strategies based on organocatalysis [23][24][25][26] and kinetic resolution using enzymes such as Candida antarctica lipase B, which was shown to be efficient in the resolution of racemic β-amino acids under various conditions [27][28][29][30]. Among recent developments

• applications on a large scale [45][46]. Very recently, Hernández, Frings, and Bolm developed a method to carry out the kinetic resolution of secondary alcohols through selective acylation using Candida antarctica lipase B, under solvent-free ball-milling conditions [47][48]. Inspired by this ground-breaking

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• transition state. Several successful results and a recent trend in organocatalytic atroposelective reactions, including enantioselective formation of chiral axes [17][18][19][20][21][22][23][24], dynamic kinetic resolution [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], kinetic

• resolution [42][43][44][45][46][47], desymmetrization [48][49][50][51][52][53][54], de novo annulation [55][56][57][58][59][60][61], and point-to-axial chirality transfer [58][59] (for reviews, see references [31][62][63]), motivated us to expand on the utility of this class of small-molecule catalysts. We

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

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• [21]. The synthesis of (R)-2 using RCM as key step is shown in Scheme 1. Enantiomerically pure 1,2-epoxyhex-5-ene (6) was obtained by Jacobsen hydrolytic kinetic resolution on commercially available 6 (Scheme 1) [22][23]. Surprisingly, the yield of 69% of the (R)-enantiomer was higher than the

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• product in high chemical yield (Figure 1b). Noyori has stated that this complex transformation is an “ideal asymmetric catalysis” [6]. There are several potential challenges in designing such a reaction, including kinetic resolution of the starting material and double stereodifferentiation [7] of

• reactive intermediates. Three important types of enantioconvergent catalysis are specifically discussed herein: type I – stereomutative, type II – stereoablative [8], and type III – parallel kinetic resolution [9]. The primary criteria for all enantioconvergent catalytic reactions are: The starting

• one enantiomer to product (Figure 2). Additionally, the rate of starting material racemization must be significantly faster than the rate of kinetic resolution in order to achieve maximum yield and selectivity. Perhaps the most well-developed class of type I enantioconvergent catalysis is dynamic

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

• reported on the results of the kinetic resolution of racemic dienes by subjecting them to a Cu(I)-catalyzed nitroso hetero-Diels–Alder reaction in the presence of chiral diphosphine ligands [147]. The best results were obtained using Walphos ligand 209 and the results of the reactions of dienes 205 with 2

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• -von-Laue-Straße 7, D-60438 Frankfurt am Main, Germany 10.3762/bjoc.12.176 Abstract Starting from (S)-β-phenylalanine, easily accessible by lipase-catalyzed kinetic resolution, a chiral triamine was assembled by a reductive amination and finally cyclized to form the title compound 10. In the crystals

• base the retro-aldol reaction of some cycloadducts with kinetic resolution of the enantiomers. In three cases, the retro-aldol products (48–83% ee) could be recrystallized to high enantiopurity (≥95% ee). The absolute configuration of several compounds is supported by anomalous X-ray diffraction and by

• chemical correlation. Keywords: absolute configuration; anthrone; cycloaddition; kinetic resolution; lipase; Introduction In guanidinium ions charge delocalization is an important factor to stabilize the protonated form. As a result, guanidines are exceptionally strong nitrogen bases. As part of the

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• ′-dioxide–Sc(III) complex promoted Baeyer–Villiger oxidation was applied as instrument for a kinetic resolution of racemic 2-substituted cyclopentanones with formation of the 6-substituted δ-lactones in up to 98% ee and >95% regioselectivity [284]. A highly regio- and enantioselective Baeyer–Villiger

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• . Work is ongoing in our laboratory to better understand and predict the matched/mismatched effect seen for chiral substrates, in particular by studying the kinetic resolution of racemic allylic alcohols. Detailed mechanistic and computational studies are underway to better understand the active catalyst

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

• achieve the catalytic kinetic resolution of readily available racemic 3-hydroxy-3-substituted oxindoles, giving the enantiopure 3-hydroxyoxindoles with excellent enantioselectivities (Scheme 45) [62]. In this reaction, the oxidant MnO2 was considered to be important for the reactvity and selectivity and

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• capsules as yocto-liter reaction flasks are capsules as a means of molecular protection, and whilst the former has continued to gain prominence, the latter was (and still is) poorly developed. To explore this idea we carried out the kinetic resolution of pairs of constitutionally isomeric esters in the

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• report on a dynamic system combining a 1,1,3,3-tetramethylguanidine (TMG)/ZnI2-catalyzed diastereoselective cascade sulfa-Michael/nitroaldol reaction followed by lipases catalyzed kinetic resolution using two representative trans-β-methyl-β-nitrostyrenes and 1,4-dithiane-2,5-diol as reagents [21]. One

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• tested and the desired products were isolated in good to excellent yields (up to 98%), diastereoselectivities (up to 99:1) and enantioselectivities (up to 98%). In 2010, Xie and co-workers reported the kinetic resolution of racemic 3-nitro-2H-chromenes 130 catalyzed by Takemoto’s organocatalyst 77

• smoothly for a wide range of substrates with high stereoselectivity, that fact is inconsistent with the current literature as the sulfa-Michael reaction is not catalyzed efficiently by this catalyst. In order to explain the high selectivity of the reaction, they proposed a dynamic kinetic resolution (DKR

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• , diastereoselective reduction of the cross-benzoin products with NaBH4 afforded valuable syn-diol products. Goodman and Johnson disclosed a dynamic kinetic resolution of β-halo-α-ketoesters via NHC-catalysed asymmetric cross-benzoin reaction. Here, the cross-benzoin reaction of aromatic aldehydes with β-stereogenic-α

• ketones developed by Enders. Cross-benzoin reactions of aldehydes and α-ketoesters. Enantioselective cross-benzoin reactions of aliphatic aldehydes and α-ketoesters. Dynamic kinetic resolution of β-halo-α-ketoesters via cross-benzoin reaction. Enantioselective benzoin reaction of aldehydes and alkynones

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

• reaction, the trifluoroacetamido moiety present in the ortho position of the aryl halides plays an important role in enantiocontrol (Scheme 15). Copper-catalyzed asymmetric aryl C–N coupling through desymmetrization and kinetic resolution strategies In the past, the asymmetric version of aryl C–N/O/S

• system through an “indirect” way, either by asymmetric desymmetrization or kinetic resolution [40][41][42][43][44]. In most cases, the enantioselectivities were not satisfactory. Recently, a copper catalytic system became another option toward asymmetric N-arylation reactions in term of improving

• good yields and with excellent enantioselectivities (Scheme 20). Kinetic resolution is another strategy for asymmetric aryl C–N coupling reactions. Cai et al. [50] developed a copper-catalyzed asymmetric intramolecular N-arylation of rac-2-amino-3-(2-iodoaryl)propionates and rac-2-amino-4-(2-iodoaryl