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

Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

• Emeline Rideau and
• Stephen P. Fletcher

Beilstein J. Org. Chem. 2015, 11, 2435–2443, doi:10.3762/bjoc.11.264

• than all-carbocyclic 1, it appears that 2a undergoes kinetic resolution. However, this system is clearly complicated by the fact that the majority of 2a is consumed during byproduct 11's formation. In the phosphate system based on 2d, the ee of product 5 was found to increase during the course of the

Chiral Cu(II)-catalyzed enantioselective β-borylation of α,β-unsaturated nitriles in water

• Lei Zhu,
• Taku Kitanosono,
• Pengyu Xu and
• Shū Kobayashi

Beilstein J. Org. Chem. 2015, 11, 2007–2011, doi:10.3762/bjoc.11.217

• kinetic resolution of racemic β-hydroxynitriles [21][22], are fascinating candidates for the development of many synthetically feasible derivatives. When studying these systems, it is important to understand how the conformation of the substrate geometry correlates with its reactivity and

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• in gene therapy. Mexiletine (38) was incorporated into amphiphilic poly(amine-co-ester)s through a two-step lipase catalyzed procedure. Firstly, racemic mexiletine was used in a biocatalyzed kinetic resolution to form the amide with pure (R)-amide with methyl 3-(bis(2-hydroxyethyl)amino)propanoate

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

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• ]. Electrooxidation to prepare a chiral oxidation mediator and application to the kinetic resolution of sec-alcohols [58]. Electrooxidation reactions on 4-membered ring systems [68]. An electrochemical multicomponent reaction where a carbon felt anode and platinum cathode were utilised and carried out at −78 °C [22

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• chemoenzymatic route. The central chiral building block, 1-(10H-phenothiazin-10-yl)propan-2-ol, was obtained via a lipase-mediated kinetic resolution protocol, which furnished both enantiomeric forms, with superb enantioselectivity (up to E = 844), from the racemate. Novozym 435 and Lipozyme TL IM have been

• columns. Keywords: ethopropazine; lipase-catalyzed kinetic resolution; Mosher methodology; promethazine; stereodivergent synthesis; Introduction Since enantiomorphs of biologically active compounds exhibit significant differences in their pharmacokinetic and pharmacodynamic behavior, optical purity of

• , mainly associated with periodontitis and osteoporosis. Moreover, kinetic resolution of the enantiomers of the key intermediate 1-(10H-phenothiazin-10-yl)propan-2-ol may simultaneously provide access to another valuable compound in enantioenriched form, that is: ethopropazine (profenamine). In turn, this

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• obtained. These include the selective reduction of β-enamino ester enantiomers [14], enzyme-catalyzed kinetic resolution [15], and a variety of asymmetric syntheses, for example, the enantioselective syntheses of β-lactams followed by ring opening [16][17], or the enantioselective desymmetrization of

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

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

cis–trans Isomerization of silybins A and B

• Michaela Novotná,
• Radek Gažák,
• David Biedermann,
• Florent Di Meo,
• Petr Marhol,
• Marek Kuzma,
• Lucie Bednárová,
• Kateřina Fuksová,
• Patrick Trouillas and
• Vladimír Křen

Beilstein J. Org. Chem. 2014, 10, 1047–1063, doi:10.3762/bjoc.10.105

• propose a mechanism for the cis–trans-isomerization processes. Results and Discussion Chemistry In our previous work on the enzymatic kinetic resolution of silybin [4][5], BF3∙OEt2 in EtOAc was found to catalyze the transesterification of silybin to yield not only 23-O-acetylsilybin (2, ca. 90%), but two

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• enantioselective α-fluorination of racemic α-chloroaldehydes with a chiral organocatalyst yielded the corresponding α-chloro-α-fluoroaldehydes with high enantioselectivity. It was also revealed that kinetic resolution of the starting aldehydes was involved in this asymmetric fluorination. This paper describes the

• (Scheme 1) [8]. These results suggested that kinetic resolution of the starting aldehydes was involved in this asymmetric fluorination. To collect further information on the reaction mechanism, we sought to determine the absolute configuration of 4a. Recently, we reported the enantioselective synthesis of

• enantiofacial selection during electrophilic fluorination of the enamine intermediates, but also a high level of kinetic resolution of the starting aldehydes. From these results, we proposed a reaction mechanism for the fluorination of α-chloroaldehydes, as shown in Scheme 4. Catalyst (S)-1 reacts with (R)-2a

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

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• to get (−)-gigantamide by lipase catalyzed kinetic resolution in line with the reported method for R-jatropham [23] was not successful. Conclusion In conclusion, a facile synthesis of (±)-grandiamide D (5), dasyclamide (6) and gigantamide A (7) and asymmetric synthesis of natural (+)-grandiamide D (5

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

• under a variety of conditions (Table 4). In the absence of a Ru catalyst, a kinetic resolution occurs and 26 and the resolved alcohol (2S)-21 were isolated in similar yields (Table 4, entry 1). Upon addition of Shvo’s catalyst C, only minor amounts of the desired acetate 26 and no resolved alcohol were

A protecting group-free synthesis of the Colorado potato beetle pheromone

• Zhongtao Wu,
• Manuel Jäger,
• Jeffrey Buter and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2013, 9, 2374–2377, doi:10.3762/bjoc.9.273

• . Although the approach is elegant, (S)-linalool required for natural (S)-1 is not commercially available. In 2005, Mori employing lipase-catalyzed kinetic resolution of (±)-2,3-epoxynerol as the key step, synthesized both (S)- and (R)-1 in gram quantities with high ee. In Chauhan’s work, Grignard reaction

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

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• ; however, this proceeded in only modest yield and diastereoselectivity (53%, 2.8:1 syn/anti). Although the ratio of syn/anti epoxide diastereomers could be enhanced by subjecting the mixture to hydrolytic kinetic resolution [39], greater throughput could be obtained by converting 25 to the tert-butyl