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

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

• Elizabeth P. Jones,
• Peter Jones,
• Andrew J. P. White and
• Anthony G. M. Barrett

Beilstein J. Org. Chem. 2011, 7, 1570–1576, doi:10.3762/bjoc.7.185

• electrophile in the presence of boron trifluoride etherate (Table 1, entry 10) gave alcohol 6j. When (S)-propylene oxide was used instead there was no reaction, and indeed Schöllkopf noted significant levels of kinetic resolution when such reactions were performed with racemic oxiranes [23]. In our previous

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

• immobilized Candida antarctica lipase B (Novozym 435) was used as a heterogeneous catalyst in the kinetic resolution of the alcohol 22 [30]. Racemization of the unreacted (S)-22 was achieved with acidic zeolite catalysts. Both heterogenous catalysts were coated with ionic liquids for improved stability of the

• and solvent-free environment [38]. In the first noncatalyzed thermal aza-Michael addition performed at 80 °C, the racemic ester rac-46 is formed from cheap starting materials benzylamine (44) and trans-ethylcrotonate (45) (Scheme 14). Subsequently, Novozym 435 is applied for the kinetic resolution of

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

• . Different examples can be found, in this regard, in the literature. The most common transformations are the kinetic resolution (KR) of secondary alcohols. For example, Matsuda has reported the use of the commercially available supported lipase Novozym 435 for the kinetic resolution of aromatic and

• mL·min–1, H2:substrate ratio = 4). The racemic alcohol (75% conversion for the first step) was directly fed to a second catalytic reactor containing the supported biocatalyst to carry out the kinetic resolution (40–50 °C, Novozym 435 or CLEAS as the immobilized enzyme). Although only moderate conversions

• flow biocatalytic systems in which the IL phase acts as the stationary phase and the scF becomes the mobile phase [98]. Pioneering work in this field was carried out by the groups of Lozano and Leitner and Reetz [99][100]. Both groups studied the kinetic resolution of phenylethanol with Candida

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

• Abigail Page and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1327–1333, doi:10.3762/bjoc.7.156

• intermediate as the reaction progresses. The results with Bu3SnCl suggest that lithiation generates an approximately 20:1 mixture of configurationally stable diastereoisomeric benzyllithiums of which the minor is significantly more reactive than the major (see below). A form of kinetic resolution occurs in

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• ]. Additionally, they can be obtained in an enantiomerically enriched form by Sharpless kinetic resolution [41]. In order to ensure regioselective ring-opening of the cyclopropene ring, cyclopropenyl carbinols possessing a trisubstituted endocyclic alkene were considered with the hope that a secondary cyclopropyl

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• substrate 44 is more difficult. A higher loading of the catalyst and higher temperature are required to produce the enantioenriched thioether 45 even in moderate yield and acceptable er (Scheme 17). Despite the poor yield obtained with this substrate, similar conditions lead to catalytic kinetic resolution

• thioether 29. Thioethers 33 prepared from phosphinites 31. Preparation of enantiomerically pure thiol 39. Thioethers prepared by a modified Mitsunobu reaction. Nucleophilic conjugate addition. Asymmetric addition to cyclic enones. Preparation of thioether 45. Catalytic kinetic resolution of the enantiomers

Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B

• Silke Dubberke,
• Muhammad Abbas and
• Bernhard Westermann

Beilstein J. Org. Chem. 2011, 7, 421–425, doi:10.3762/bjoc.7.54

• was filtered and evaporated to dryness. After the addition of a catalytic amount of hydroquinone the dark brown residue was heated at 180 °C for 1 h and then purified by distillation under reduced pressure to give (±)-1c (1.70 g, 40%). The kinetic resolution was carried out as follows: To phosphate