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

• 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

• the catalytic enantioselective synthesis of axially chiral 3,3’-bisindole backbones from prochiral substrates [66]. The atroposelective synthesis of a new class of 3,3'-bisindoles 51 with axial and central chirality by dynamic kinetic resolution of 2-substituted 3,3'-bisindoles via asymmetric

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

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

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

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

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

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

• success. Continuing development in this field may lead to the “ideal asymmetric catalysis” [3]. Enantioconvergent methods. Stereomutative enantioconvergent catalysis. Stereoablative enantioconvergent catalysis. Enantioconvergent parallel kinetic resolution. Dynamic kinetic resolution by hydrogenation

• kinetic resolution (DKR) [10][11][12][13][14][15][16]. Processes of this type were first described by Noyori in the enantioselective hydrogenation of β-ketoesters ((±)-1 → 2, Scheme 1) [6]. In the event, the resident stereocenter of the substrate 1 can epimerize via tautomerization to the enol form

• 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

(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

• 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

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• P-chiral phosphorothioates, a trivalent dinucleoside phosphorus moiety is required that undergoes rapid epimerization under the sulfurization conditions – that is, the goal was to carry out a dynamic kinetic resolution with formation of a single epimeric phosphorothioate. In order to carry out the

• required dynamic kinetic resolution, it was hypothesized that acylphosphonites 1 might undergo rapid epimerization by comparison to their known acylphosphine analogs 2 (Figure 1). Mislow previously showed that trialkyl and triarylphosphines slowly undergo epimerization only at temperatures above

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• [30] and dynamic kinetic resolution [31]. However, in contrast to these routes, we desired to develop a synthesis of O-acylated (2S,3S)-3-hydroxyleucine derivatives which should be easily scalable and would enable O-acylation after construction of the stereocenters with only few changes in the

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• -coupling of benzyl or alkyl halides with racemic secondary phosphines have been developed. These reactions were catalyzed by chiral platinum or ruthenium complexes. The enantioselectivity is based on a dynamic kinetic resolution. Upon reaction with the catalyst precursor containing a chiral ligand (L*), a

• enantioselectivity of the end products 10 is related to the ratio of the diastereomeric phosphido complexes 34. The major phosphine product is derived from the major diastereomeric phosphido complex. The dynamic kinetic resolution approach has been reviewed in more detail by Glueck [57][58]. Scheme 10 relates to

• approach towards the widely used arylphosphines that are inaccessible by hydrophosphination. Recent advances in this area concern the synthesis of P-stereogenic phosphines through a dynamic kinetic resolution of racemic secondary phosphines in a metal-catalyzed P–H/aryl halide coupling. C(sp2)–P bond

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• kinetic resolution [156], albeit with unsatisfactory enantiomeric excess. The undesired enantiomer was then selectively cleaved using another enzyme with reversed selectivity to give enantiopure pyranone 181. Cyclopropanation was achieved using a Michael addition initiated ring closure yielding diester

• , see Scheme 22) [152], isolated from the leaves of Gelsemium elegans was accomplished by Fukuyama and coworkers [153][154]. Starting from furfuryl alcohol (179) an epoxide initiated Achmatowicz reaction [155] took place to give α,β-unsaturated pyrane 180. Next in line was an enzyme catalyzed dynamic

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• carboxylic acid and (iii) a Ru–lipase-catalyzed dynamic kinetic resolution to establish the desired configuration at C9. Ring closure was accomplished by macrolactonization. Curvulide A was synthesized from stagonolide E through Sharpless epoxidation. Keywords: dienes; enzyme catalysis; lactones; metathesis

• resolution (Scheme 4). These unsuccessful attempts to establish the correct configuration at C9 led to a revision of the synthetic strategy. We decided to investigate a dynamic kinetic resolution (DKR) approach at an earlier stage of the synthesis and identified the secondary alcohol 21 as a promising

• -diene-3,4-diol. Key elements of the stagonolide E synthesis are the two-directional functionalization of the enantiopure, C2-symmetrical starting material through cross metathesis and a one-flask ring-closing metathesis/base-induced ring-opening sequence, a Ru–lipase-catalyzed dynamic kinetic resolution

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• positive discrepancy between the cis/trans ratio of the imine and the corresponding product diastereomeric ratio – see reference [40]. In that study, the non-linearity is explained by referring back to Harada’s study [51] as discussed in the Historical Perspective section, to invoke a dynamic kinetic

• resolution. Furthermore, in a further effort to investigate the possibility of metal catalyst induced isomerization, we reduced imines 2a–e using significantly higher loadings of Pd/C or Pt/C at 22 °C than noted in Table 2, but found no inconsistency pointing to isomerization.) These overall findings are

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• unprecedented asymmetric domino thio-Michael–Michael process, involving dynamic kinetic resolution, was reported by Wang et al. [72] using cinchona alkaloid amine-thiourea XXXIb as catalyst at a low catalytic loading of 2 mol %. Reaction of 3-(2-mercaptophenyl)-2-propenoic acid ethyl esters 50 with α,β

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• . Lozano and coworkers reported on a continuous, chemoenzymatic dynamic kinetic resolution (DKR) process for the production of (R)-1-phenylethyl propionate (24) from (rac)-1-phenylethanol (22) and vinyl propionate (23) (Scheme 8) [29][30][31]. In a multiphase packed-bed reactor, commercially available

• -acetylneuraminic acid (17) in a continuously operated enzyme membrane reactor. E1: Epimerase; E2: Aldolase [27]. Chemo-enzymatic epoxidation of 1-methylcyclohexene (18) in a packed-bed reactor (PBR) containing Novozym 435 (E) [28]. Continuous production of (R)-1-phenylethyl propionate (24) by dynamic kinetic

• resolution of (rac)-1-phenylethanol (22) in supercritical CO2 in a packed-bed reactor loaded with acidic zeolite (A) and Novozym 435 (E) [30]. Synthesis of D-xylulose (28) from D,L-serine (26) and D,L-glyceraldehyde (25) in a continuously operated enzyme membrane reactor. E1: D-Amino acid oxidase; E2

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• , the process was carried out at 80 °C with yields of 93% for more than 10 h without any appreciable deactivation of the enzyme. Considering enantioselective transformations, the dynamic kinetic resolution (DKR) of phenylethanol was studied under continuous flow in scCO2. This was easily achieved by the

• combination of a supported enzyme (Novozym 435) and a supported acid catalyst, both covered by a thin layer of an IL. This has allowed the development of the continuous chemoenzymatic dynamic kinetic resolution of the corresponding racemic alcohols with yields of up to 80% and enantioselectivities of about 91

Development of dynamic kinetic resolution on large scale for (±)-1-phenylethylamine

• Lisa K. Thalén and
• Jan-E. Bäckvall

Beilstein J. Org. Chem. 2010, 6, 823–829, doi:10.3762/bjoc.6.97

• Lisa K. Thalen Jan-E. Backvall Stockholm University, Department of Organic Chemistry, Arrhenius Laboratory SE-106 91, Stockholm, Sweden 10.3762/bjoc.6.97 Abstract Candida antarctica lipase B (CALB) and racemization catalyst 4 were combined in the dynamic kinetic resolution (DKR) of (±)-1

• donor. Keywords: dynamic kinetic resolution; kinetic resolution; racemization; Shvo; Candida antartica lipase B; Introduction Chiral amines are important building blocks in the synthesis of many pharmaceuticals, fragrances, and agricultural products, and it is therefore important to develop methods

• product mixture. However, by racemizing the slower reacting enantiomer in situ, in a process known as dynamic kinetic resolution (DKR) [11], a theoretical yield of 100% can be achieved. We have previously developed a highly efficient protocol for the DKR of primary amines using Candida antarctica lipase B

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• co-workers have designed a continuous-flow reactor system, PASSflow [40], based on the use of a functionalizable monolithic rod derived from a glass/polymer composite. This device was used for the dynamic kinetic resolution of epibromohydrin 32, using a monolith reactor functionalized with a chiral

• flow. Asymmetric synthesis of ß-lactams. α-Chlorination of acid chlorides in flow. Asymmetric Michael reaction in continuous flow. Enantioselective addition of Et2Zn to benzaldehyde using monolithic chiral amino alcohol. Continuous-flow hydrolytic dynamic kinetic resolution of epibromohydrin (32

Large- scale ruthenium- and enzyme- catalyzed dynamic kinetic resolution of (rac)-1-phenylethanol

• Krisztián Bogár,
• Belén Martín-Matute and
• Jan-E. Bäckvall

Beilstein J. Org. Chem. 2007, 3, No. 50, doi:10.1186/1860-5397-3-50

• Krisztian Bogar Belen Martin-Matute Jan-E. Backvall Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden 10.1186/1860-5397-3-50 Abstract The scale-up of the ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR) of (rac)-1

• ][28] and recently this approach has been extended to dynamic kinetic resolution (DKR) by combining the enzymatic resolution with a metal-catalyzed racemization. [29][30][31][32][33][34][35][36][37] Today, many stable lipases are commercially available and they are frequently used in synthetic organic

• . Experimental See Supporting Information File 1 for experimental data. Racemization catalyst 1. DKR of 1-phenylethanol under an Ar atmosphere (top) and DKR of 1-phenylethanol under an O2 atmosphere (bottom). Dynamic kinetic resolution of 1-phenylethanol (2) under different reaction conditions.a Supporting