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

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• , which was then converted to enantiopure 2 via an enzymatic kinetic resolution [12]. The Diels–Alder reaction was effectively employed in both of these syntheses for construction of the two quaternary carbons at the C1 and C5 positions of ryanodine (highlighted in gray). However, the current route to

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• using enzyme-catalyzed kinetic resolution of 1-(β-hydroxypropyl)azoles as a key step. We have shown that this attempt is simple and allows the preparation of new types of optically active ionic liquids. Inhibitory activity of the newly synthesized CILs was tested towards gram-negative and gram-positive

Asymmetric desymmetrization of meso-diols by C₂-symmetric chiral 4-pyrrolidinopyridines

• Hartmut Schedel,
• Keizo Kan,
• Yoshihiro Ueda,
• Kenji Mishiro,
• Keisuke Yoshida,
• Takumi Furuta and
• Takeo Kawabata

Beilstein J. Org. Chem. 2012, 8, 1778–1787, doi:10.3762/bjoc.8.203

• ][18]. These catalysts are expected to show high catalytic activity because the introduction of substituents close to the pyridine nitrogen has been known to result in the significant decrease of the catalytic activity [19]. Catalyst 1 was demonstrated to be effective for the kinetic resolution of

• racemic diols (s: up to 12) [8] and amino alcohol derivatives (s: up to 54) [9]. Catalyst 2, readily prepared from L-proline, could be employed for the kinetic resolution of amino alcohol derivatives (s: up to 11) [10]. Chiral PPY catalysts with dual functional side chains at C(2) and C(4) of the

• , entries 1, 4 and 5). This suggests that the ee of monoacylate 6 would be amplified by the second acylation step, i.e., acylative kinetic resolution of enantioenriched monoacylate 6 produced by the asymmetric desymmetrization of the meso-substrate (Scheme 3). To confirm this issue, kinetic resolution of

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

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• type of axially chiral ligand 7 with an N-naphthyl framework (Figure 2) instead of traditional binaphthyl framework [15]. Their palladium complexes 8 showed high stereoselectivities in asymmetric allylic arylations to achieve the kinetic resolution of Morita–Baylis–Hillman adducts, affording up to 99

Facile isomerization of silyl enol ethers catalyzed by triflic imide and its application to one-pot isomerization–(2 + 2) cycloaddition

• Kazato Inanaga,
• Yu Ogawa,
• Yuuki Nagamoto,
• Akihiro Daigaku,
• Hidetoshi Tokuyama,
• Yoshiji Takemoto and
• Kiyosei Takasu

Beilstein J. Org. Chem. 2012, 8, 658–661, doi:10.3762/bjoc.8.73

• –10 mol %) catalyzes the isomerization of silyl enol ethers at −78 °C [6]. By using this catalyst, they remarkably achieved the kinetic resolution of racemic silyl enol ethers. To make this isomerization synthetically useful and valuable, the development of more-reactive catalysts and a facile

Tertiary alcohol preferred: Hydroxylation of trans-3-methyl-L-proline with proline hydroxylases

• Christian Klein and
• Wolfgang Hüttel

Beilstein J. Org. Chem. 2011, 7, 1643–1647, doi:10.3762/bjoc.7.193

• numerous approaches for the synthesis of tertiary alcohols with classical organic chemistry [1][2][3][4][5], enzyme-catalyzed approaches have also been successfully established, and especially, hydrolases, i.e., lipases and esterases, are used for the kinetic resolution of tertiary alcohols [6][7][8][9