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

α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

• David. M. Hodgson and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2010, 6, 978–983, doi:10.3762/bjoc.6.110

• or BF3•Et2O in CH2Cl2; aminolytic kinetic resolution [12][38]), and use of (Me3)SiHNPO(OEt)2 [39] also proved ineffective. A convenient asymmetric access was eventually developed, starting with ring-opening of commercially available (R)-1,2-epoxybutane (15) using ammonia, which gave β-amino alcohol

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

• amination of prochiral ketones [8]. Of these methods kinetic resolution using enzymes is often favored due to its simplicity [9][10]. The main disadvantages of kinetic resolution are that only a maximum yield of 50% can be achieved and that the remaining unreacted starting material must be removed from the

Three step synthesis of single diastereoisomers of the vicinal trifluoro motif

• Vincent A. Brunet,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2009, 5, No. 61, doi:10.3762/bjoc.5.61

• . Results and Discussion The chemistry was initiated from allylic alcohol 2 which can readily be prepared in enantiomerically pure form by hydrolytic kinetic resolution of vinyl epoxide 1 following Jacobsen’s protocol [13] (Scheme 3). Diol 2 was converted to tosyl ester 3 in a regioselective manner

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

• , larger scale run (10 mmol) was performed continuously over a 6 day period (until complete consumption of epibromohydrin), providing the desired (R)-diol 34 also in similar yield and enantioselectivity. The hydrolytic kinetic resolution of a terminal epoxide in continuous flow has also been investigated

• have been developed recently, including processes using alternative solvents such as ionic liquids and/or scCO2 [56][57][58][59][60][61]. The kinetic resolution of racemic 1-phenylethanol 54 was performed continuously in scCO2, using an immobilized lipase (Candida antarctica, Novozym 435) and vinyl

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• the kinetic resolution manifold, providing the key bis-THF fragment 316 as a single diastereomer. Protodesilylation of the bis-THF 316 was accomplished by treatment with TBAF to give tetraol 317. The butenolide ring was then installed completing the total synthesis of (+)-bullatacin (311). In 2006

Diastereoselective and enantioselective reduction of tetralin- 1,4-dione

• E. Peter Kündig and
• Alvaro Enriquez-Garcia

Beilstein J. Org. Chem. 2008, 4, No. 37, doi:10.3762/bjoc.4.37

• precedent for procedures for the asymmetric synthesis of 9. The first involves as the key step kinetic resolution by enzymatic hydrolysis of the corresponding acetate with porcine pancreatic lipase giving (−)-9 in 47% yield and 95% ee [13]. A second approach uses a Pd-catalyzed asymmetric oxidation of meso

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

Conformational rigidity of silicon- stereogenic silanes in asymmetric catalysis: A comparative study

• Sebastian Rendler and
• Martin Oestreich

Beilstein J. Org. Chem. 2007, 3, No. 9, doi:10.1186/1860-5397-3-9

• metal-catalyzed asymmetric transformations as exemplified by (1) the hydrosilylation of alkenes constituting a chirality transfer from silicon to carbon and (2) the kinetic resolution of racemic mixtures of alcohols by dehydrogenative silicon-oxygen coupling. In this investigation, a cyclic and a

• were reported, [6] namely the inter- [7] as well as intramolecular [8] chirality transfers from silicon to carbon. Moreover, we had demonstrated that chiral silanes resolve racemic mixtures of alcohols in a non-enzymatic, transition metal-catalyzed kinetic resolution. [9] During our ongoing

• -catalyzed kinetic resolution of donor-functionalized alcohols capable of two-point binding. The reagent-controlled hydrosilylation of norbornene derivative 2 with silane 1a proceeds with a perfect chirality transfer (rac-1a → rac-3a, Scheme 1). [8] Mechanistic investigation of the nature of the

Towards practical biocatalytic Baeyer- Villiger reactions: applying a thermostable enzyme in the gram- scale synthesis of optically- active lactones in a two-liquid- phase system

• Frank Schulz,
• François Leca,
• Frank Hollmann and
• Manfred T. Reetz

Beilstein J. Org. Chem. 2005, 1, No. 10, doi:10.1186/1860-5397-1-10

• catalysis (Table 1). We were pleased to observe essentially identical enantioselectivities when applying in vitro catalysis (for ketone 1 compare Table 1; the kinetic resolution of ketone 6 is characterized by a selectivity factor of E = 100, the enantiopurity of lactone 7 being 95.4% ee (R)). Ketone 1

• substrate in cyclohexane. The kinetic resolution reached the optimal 50% conversion after about 24 h. Upscaling to gram-quantities was straight-forward without changes in the procedure. Overall we obtained turnover numbers (TONs) of more than 30000 for the P3-PAMO-catalyzed BV-oxidation of ketone 1, which

Mixtures of monodentate P-ligands as a means to control the diastereoselectivity in Rh-catalyzed hydrogenation of chiral alkenes

• Manfred T. Reetz and
• Hongchao Guo

Beilstein J. Org. Chem. 2005, 1, No. 3, doi:10.1186/1860-5397-1-3

• described earlier.[34] Since the substrates 1 and 5 were used as racemates, kinetic resolution may be involved when the chiral ligands are employed, i.e., diastereoselectivity may change with conversion. This aspect was not a subject of the present study. In all hydrogenation reactions the standard