Valence isomerization of cyclohepta-1,3,5-triene and its heteroelement analogues

• Helen Jansen,
• J. Chris Slootweg and
• Koop Lammertsma

Beilstein J. Org. Chem. 2011, 7, 1713–1721, doi:10.3762/bjoc.7.201

• almost similar boat puckering for all. From the racemization of substituted benzene oxides (Scheme 2), the oxepine ring inversion barrier was estimated at 6.5 kcal·mol−1 at 135 K [45][46], which is similar to the 3.5 kcal·mol−1 calculated for the parent oxepine (3) at the QCISD(T)/6-31G(d) level [40

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

• . Hydrolysis of the sterically less hindered adducts gave the corresponding quaternary amino acids with no racemization, whereas hydrolytic ring opening gave the corresponding valine dipeptides from bulkier bislactims. Keywords: aryl amino acids; arynes; asymmetric; multicomponent; quaternary; Introduction

Synthesis of (−)-julocrotine and a diversity oriented Ugi-approach to analogues and probes

• Ricardo A. W. Neves Filho,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2011, 7, 1504–1507, doi:10.3762/bjoc.7.175

• % yield in optically pure form [16]. To alkylate the imide-moiety, glutarimide 3 was reacted with phenylethyl bromide in the presence of potassium carbonate at room temperature. The desired compound 4 was obtained in 98% isolated yield, but analysis revealed racemization. Indeed, the equilibration at the

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

• 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

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

• mixture of zeolite CP811E-150 as the acid catalyst for the racemization and CALB supported on a SILLP based on bead-type PS-DVB resins [106]. Good results were obtained when the zeolite catalyst was coated with a small amount of an IL. This follows the same trend observed in the case of SILPs

Synthesis of enantiomerically enriched (R)-¹³C-labelled 2-aminoisobutyric acid (Aib) by conformational memory in the alkylation of a derivative of L-alanine

• Stephen P. Fletcher,
• Jordi Solà,
• Dean Holt,
• Robert A. Brown and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1304–1309, doi:10.3762/bjoc.7.152

• e.r. of the products 5 and 6*) was strongly dependent on the conditions of the reaction and in particular on the time allowed between deprotonation of 3 and the addition of 13CH3I. Presumably, shorter reaction times minimise the extent of racemization of the intermediate enolate 4 [36]. Addition of

A novel high-yield synthesis of aminoacyl p-nitroanilines and aminoacyl 7-amino-4-methylcoumarins: Important synthons for the synthesis of chromogenic/fluorogenic protease substrates

• Xinghua Wu,
• Yu Chen,
• Herve Aloysius and
• Longqin Hu

Beilstein J. Org. Chem. 2011, 7, 1030–1035, doi:10.3762/bjoc.7.117

• groups such as Cbz and Pht. The use of phosphorus pentaoxide for peptide synthesis was also reported, but racemization could occur under these reaction conditions [10][11]. Phosphorus oxychloride was another condensing agent used to synthesize various N-protected aminoacyl-pNAs in yields between 70% and

• 90% [12]. The proposed mechanism implies in situ activation of carboxylic acid by formation of the active mixed anhydride with phosphorodichloridic acid. Although the authors demonstrated that the synthesis was simple and free of racemization, this method required unfavorable anhydrous pyridine as a

• racemization, it does not result in satisfactory yields. Because of these limitations of the existing methods, there is still a need to develop a generally applicable method for the synthesis of aminoacyl-pNAs. Conjugation of Nα-protected amino acids with fluorogenic 7-amino-4-methylcoumarin (AMC) is similarly

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• form, but in methanol-d4 the equilibrium shifts completely to the pyridinol tautomer. Subsequent transformations of the prepared pyridine derivatives To prove the enantiopurity of the pyridines derived from carboxylic acids and nitriles, which are prone to racemization, i.e., substrates with tertiary

• diastereomeric compounds obtained from racemic starting materials unambiguously shows that the sequence proceeds without noticeable racemization, since 49, 50 and 51 were obtained in diastereomeric pure form (Table 2) as judged by 1H NMR analysis (estimated error 3–5%). For instance, the signal of the methoxy

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• enriched secondary propargyl alcohols led to the chiral oxetan-3-one with no apparent racemization (Scheme 20). 3 Gold-catalyzed C–N bond formations Many organic compounds containing nitrogen exhibit important biological and pharmaceutical properties. As with gold-catalyzed C–O bond formation, the directly

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• or stereoselective epoxidation followed by regioselective epoxide opening) produced the racemic iminocyclitols (18–20) in good overall yields (Scheme 3). In addition, Blechert showed that this method was more adaptable as it could also yield enantiopure 18–20, provided that racemization was avoided

• 69 provides an attractive starting point since it reacts with organometallic reagents with a high degree of diastereoselectivity and minimal racemization. N-allylation (allyl iodide/NaH; 95% yield) of an intermediate derived from 70 gave the diolefin product 71, which was then subjected to RCM

Stereogenic boron in 2-amino-1,1-diphenylethanol-based boronate–imine and amine complexes

• Sebastian Schlecht,
• Walter Frank and
• Manfred Braun

Beilstein J. Org. Chem. 2011, 7, 615–621, doi:10.3762/bjoc.7.72

• complex 10 was established by separation of the enantiomers. Racemization barriers were found to be in the same range for both amine and imine complexes (100–110 kJ/mol). Keywords: boron; chirality; coordination chemistry; crystal structure; stereochemistry; Introduction Enantiomerism of main group

• have been able to obtain boronate–imine complexes 4 with boron as a stable stereogenic center (Scheme 1). Their racemization barrier was measured and the absolute configuration of the isolated enantiomers was determined by a comparison of the measured and calculated CD spectra [18]. In this article, we

• boronate–amine complex 10 on the other hand, the racemization barrier of the latter was determined. For this purpose, a sample of the enantiomerically pure complex 10 was heated in n-decane at 60 °C, and the decay of the optical purity was followed by chiral HPLC. Thus, the racemization rate at 325.4 K was

Complete transfer of chirality in an intramolecular, thermal [2 + 2] cycloaddition of allene-ynes to form non-racemic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2011, 7, 601–605, doi:10.3762/bjoc.7.70

• biradical intermediate, but the tert-butyl group hinders rotation around the carbon–carbon bond as shown in Figure 4, thus slowing racemization of the resulting radical containing carbon. This hypothesis is supported by a report by Pasto, where transfer of chiral information was incomplete in a thermal

Synthesis of 5-(2-methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene as 2,2'-disubstituted 1,1'-binaphthyls via benzannulated enyne–allenes

• Yu-Hsuan Wang,
• Joshua F. Bailey,
• Jeffrey L. Petersen and
• Kung K. Wang

Beilstein J. Org. Chem. 2011, 7, 496–502, doi:10.3762/bjoc.7.58

• determined to be 23.5 kcal/mol at 50 °C, corresponding to a half-life of 14.5 minutes for racemization [27][28]. Because the structure of 20a could be regarded as a 2,3,4-trisubstituted 1,1'-binaphthyl, the rate of rotation can be expected to be even slower. Again, in C6D6 recorded on a 600 MHz NMR

• , corresponding to a half-life of 4.5 hours for racemization [28]. The high stability of the configuration even at such an elevated temperature allows BINOL to be used in a variety of synthetic applications. The configurational stability of 20b and 20c, which could be regarded as 2,2'-disubstituted 1,1

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• , published at the same time, was synthesized by the coupling of L-aspartic acid (83) to aryl bromide 82 in 55% yield and 90% ee (Scheme 20). Under these reaction conditions, CuI was found to be the copper source that caused the least amount of racemization [72]. Chan–Lam arylation in the synthesis of

Thermal rearrangement of tert-butylsulfinamide

• Veera Reddy Arava,
• Laxminarasimhulu Gorentla and
• Pramod Kumar Dubey

Beilstein J. Org. Chem. 2011, 7, 9–12, doi:10.3762/bjoc.7.2

• (entry 23) or with microwave irradiation (entry 25), complete consumption of starting material was observed. In other cases (entries 4, 5, 11 and 12), 10 to 30% of the starting material was recovered without racemization. Conclusion We found that both (R and S) tert-butanesulfinamides are unstable above

Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

• Michael North and
• Marta Omedes-Pujol

Beilstein J. Org. Chem. 2010, 6, 1043–1055, doi:10.3762/bjoc.6.119

• gives unprotected cyanohydrins which are prone to racemization. Pre-eminent amongst the synthetic catalysts are metal(salen) complexes, especially those based on titanium (1) and vanadium (2) [1] (Figure 1). Titanium complex 1 will catalyse the asymmetric addition of TMSCN to aromatic aldehydes with 80

• concentration of 0.56 M. In each case, the enantiomeric excess of the cyanohydrin product was determined by chiral GC after conversion of the trimethylsilyl ether into the corresponding acetate by the method of Kagan [80], a process which is known to cause no racemization (Scheme 3). The results of this study

• hours followed by crystallization from ether/hexane. That no racemization occurred during this process was demonstrated by conversion of the mandelic acid into methyl mandelate followed analysis by chiral HPLC (data presented in Supporting Information File 1), which gave an enantiomeric excess of 81

Towards racemizable chiral organogelators

• Jian Bin Lin,
• Debarshi Dasgupta,
• Seda Cantekin and
• Albertus P. H. J. Schenning

Beilstein J. Org. Chem. 2010, 6, 960–965, doi:10.3762/bjoc.6.107

• ; organogels; racemization; self-assembly; Introduction Gelation represents a macroscopic manifestation of self-assembled molecules. Impressive supramolecular architectures have been reported in which the self-assembled molecules immobilize solvent to produce a gel phase. Carefully designed self complementary

• that these hydrogen-bonded dimers or tetramers subsequently stack via π-π interaction and via van der Waals interactions into bundled fibers. Racemization The racemization of R-3 was investigated by chiral HPLC. After adding 1 equivalent of DBU to a solution of R-3 in octane at room temperature

• , samples were collected over time and the enantiomeric purity was measured. Racemization was not observed in the gel state (5 mM) after 18 hours, whilst after heating and cooling precipitation was observed. At a concentration of 1 mM, where self-assembled fibers are present, the ee of the solution

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

• (CALB) as the enzyme and 4 as the racemization catalyst (See Scheme 1 for an example of the previously developed protocol with isopropyl acetate as the acyl donor providing 2 as the amide product) [12][13]. The Jacobs–De Vos group showed that palladium on an alkaline earth support in combination with an

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• pure sulfoxide was used as starting material, no racemization was detected [40]. 1-Alkynyl sulfones 38 are prone to addition of organocopper reagents. However, the stereochemistry of the resulting vinyl sulfones 39 appear to be dependent on the relative amounts of copper(I) bromide as well as the

RAFT polymers for protein recognition

• Alan F. Tominey,
• Julia Liese,
• Sun Wei,
• Klaus Kowski,
• Thomas Schrader and
• Arno Kraft

Beilstein J. Org. Chem. 2010, 6, No. 66, doi:10.3762/bjoc.6.66

• polymer backbones. They also pose fewer racemization problems which often accompany proteinogenic amino acids in peptidic environments. In recent years, our group has developed water-soluble linear polymeric protein binders which contained one or more different binding monomers and displayed micromolar

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• stereoretentive CF3 transfer. High enantioselectivities in the range 93–97% were measured for the corresponding alcohols because of post-reaction racemization of aldehydes. Although the scope of this asymmetric reaction is limited to aldehydes, the level of enantioselectivity is superior to that obtained in the

Ring strain and total syntheses of modified macrocycles of the isoplagiochin type

• Andreas Speicher,
• Timo Backes,
• Kerstin Hesidens and
• Jürgen Kolz

Beilstein J. Org. Chem. 2009, 5, No. 71, doi:10.3762/bjoc.5.71

• and quantum chemical CD (circular dichroism) investigations, the absolute configuration of the first natural compound of this type, isoplagiochin C from P. deflexa, was established as (PA)-1 and the energy of racemization was calculated and measured to be 102 kJ/mol, approximately [13]. The

• stereochemical correlation between isoplagiochin C (1) and isoplagiochin D (2) was also confirmed experimentally by hydrogenolysis of enantiopure samples of (PA)-1 to give and (PA)-2 (Scheme 1), and of (MA)-1 to give and (MA)-2, respectively, without any racemization [14]. The natural compounds isoplagiochin D

The first preparative solution phase synthesis of melanotan II

• Vladimir V. Ryakhovsky,
• Georgy A. Khachiyan,
• Nina F. Kosovova,
• Elena F. Isamiddinova and
• Andrey S. Ivanov

Beilstein J. Org. Chem. 2008, 4, No. 39, doi:10.3762/bjoc.4.39

• 8-fold excess of DCC as the coupling agent and 1-hydroxybenzotriazole (HOBt) as a racemization suppressant. The yield of the cyclized product 12 was 31%, very close to the reported 30% yield for solution-phase cyclization of a related linear heptapeptide obtained by solid phase peptide synthesis [18

Synthesis of new triazole- based trifluoromethyl scaffolds

• Michela Martinelli,
• Thierry Milcent,
• Sandrine Ongeri and
• Benoit Crousse

Beilstein J. Org. Chem. 2008, 4, No. 19, doi:10.3762/bjoc.4.19

• single isomer without any racemization. This compound can easily afford the free amino ester which is a promising trifluoromethyl building block for the synthesis of new triazole-based trifluoromethyl oligomers. Conclusion In summary, this paper describes the synthesis of new trifluoromethyl triazole

DBFOX- Ph/metal complexes: Evaluation as catalysts for enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones

• Takehisa Ishimaru,
• Norio Shibata,
• Dhande Sudhakar Reddy,
• Takao Horikawa,
• Shuichi Nakamura and
• Takeshi Toru

Beilstein J. Org. Chem. 2008, 4, No. 16, doi:10.3762/bjoc.4.16

• that of Sodeoka's report [57]; this is presumably due to the low activity of our catalyst system which requires higher reaction temperature conditions (0 °C vs. −20 °C [57]). Racemization of the products 2 during the fluorination reaction was ruled out since no racemization was observed when 2a was