Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• in 28–64% ee [5]. In a similar fashion, Denmark’s oxazaphosphorinane cis-44a yielded keto esters 46a–c in high optical purities via conjugate addition to enones 41 followed by ozonolysis and oxidative esterification. Using diastereomer trans-44b on the other hand provided ketoesters 46a–c with only

• provided intermediate 165. Removal of the chiral auxiliary and generation of the second carboxy moiety was then achieved by ozonolysis of 165 and ensuing esterification with diazomethane to give diacid ester 166. Treatment of the latter with TBAF cleaved the TBDMS ether and gave a lactone intermediate

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• -fucopyranosyloxyamine [18] were used as sample monosaccharides for the conjugation of the dendron (Scheme 1). Synthesis of dendrons Zero, first and second generation heterobifunctional dendrons 1–3 were synthesized starting from 9-decen-1-ol (12) or selected building blocks 13 and 14 (Scheme 2) [11] by esterification

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• with classical organic acylation reactions (Friedel–Crafts reaction, esterification, amide synthesis, Scheme 1). Some of these complexes have been used as organometallic gelators [19][20], as a novel class of cytostatic compounds [26], and catalysts for unusual radical cyclizations [27][28][29][30][31

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• that enabled a late-stage, modular addition of the hydrocarbon chains; the products of which could be taken straight into the high-throughput CuAAC reaction. To this end, diol 2 was synthesised by esterification of commercially available 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid (1), according

A promising cellulose-based polyzwitterion with pH-sensitive charges

• Thomas Elschner and
• Thomas Heinze

Beilstein J. Org. Chem. 2014, 10, 1549–1556, doi:10.3762/bjoc.10.159

• Europe and were used without further treatment. Cellulose phenyl carbonate was prepared by esterification of cellulose, dissolved in N,N-dimethylacetamide (DMAc)/LiCl, applying pyridine and phenyl chloroformate [21]. 1, DS 1.92 (determined by means of 1H NMR spectroscopy after peracetylation), FTIR (KBr

Pd/C-catalyzed aerobic oxidative esterification of alcohols and aldehydes: a highly efficient microwave-assisted green protocol

• Marina Caporaso,
• Giancarlo Cravotto,
• Spyros Georgakopoulos,
• George Heropoulos,
• Katia Martina and
• Silvia Tagliapietra

Beilstein J. Org. Chem. 2014, 10, 1454–1461, doi:10.3762/bjoc.10.149

• enhanced by mild dielectric heating. Furthermore, it is a versatile green procedure which generally enables the isolation of esters to be carried out by simple filtration in almost quantitative yields. Keywords: aerobic oxidation; alcohol; esterification; heterogeneous catalysis; microwaves; Introduction

• metals. Homogeneous and heterogeneous Pd catalysts have been widely used in the selective oxidation of alcohols [36][37]. Most publications have focused on the conversion of alcohol to aldehydes or ketones [38][39]. Several examples of the heterogeneous oxidative esterification of alcohols in the

• versatility of these reactors in promoting reactions with gaseous reagents in a closed cavity [56]. In this present work, we report an efficient Pd/C-catalyzed aerobic oxidative esterification of aldehydes and alcohols in the presence of molecular oxygen in a closed MW reactor. The optimized procedure does

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• vitro and in vivo. The best performing of the products, a 40-kDa mono-PEGylated sialic acid-mediated conjugate, exhibited a 5-fold lower affinity which was however compensated by a 23-fold increase of circulation half-life [38]. PEGylation of low-molecular weight carbohydrates: Enzymatic esterification

Homochiral BINOL-based macrocycles with π-electron-rich, electron-withdrawing or extended spacing units as receptors for C₆₀

• Marco Caricato,
• Silvia Díez González,
• Idoia Arandia Ariño and
• Dario Pasini

Beilstein J. Org. Chem. 2014, 10, 1308–1316, doi:10.3762/bjoc.10.132

• ] macrocycles (compounds 3 and 4 in Scheme 1) were obtained. The compounds have average molecular D2 and D3 point group symmetries, respectively. Our optimized esterification reaction protocol is carried out at intermediate dilution levels (each reagent 20–25 mM) in CH2Cl2. Several dicarboxylic acids with

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• ester is utilised as a building block for the synthesis of 2-fluoro-2-arylacetic acid and fluorooxindole derivatives by a strategy involving nucleophilic aromatic substitution reactions with ortho-fluoronitrobenzene substrates followed by decarboxylation, esterification and reductive cyclisation

• obtained for 6a. However, corresponding attempted esterification of the salt 4f with HCl in methanol gave 2-fluoromethyl-3-nitropyridine (7) in 68% yield (Scheme 3) after purification of the crude material by column chromatography and the structure was confirmed by X-ray analysis (Figure 3). In this case

• competing decarboxylation, rather than esterification, reflects the greater stabilisation of the carbanion system formed upon decarboxylation for this system. Reductive cyclization of methyl esters 6a–e using sodium dithionite provided fluorooxindoles 8a–e in acceptable yield after isolation by column

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• modified by fatty acid acylation [97]. The synthesis of these lipidated peptides can be performed by amidation, S- or O-esterification as well as thioether or -sulfide formation. Owing to the strength of the covalent bonds, amidation and O-esterfication are preferred over the other strategies [97

• ]. Chemical synthesis of lipidated peptides is mostly performed by SPPS using the Fmoc/t-Bu strategy allowing for selective and efficient modification. Fatty acids can be incorporated into the peptide sequence at the N-terminus [98], at lysine [99] or cysteine side chains [100] and by esterification [101]. A

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

• derivatization as well as for solid-phase peptide synthesis. With respect to according motifs occurring in natural products, we have converted these building blocks into 3-O-acylated structures. Utilizing an esterification and cross-metathesis protocol, (2S,3S)-3-hydroxyleucine derivatives were synthesized, thus

• opening up an excellent approach for the synthesis of bioactive natural products and derivatives thereof for structure activity relationship (SAR) studies. Keywords: chiral pool; cross metathesis; esterification; β-hydroxy-α-amino acids; natural products; Introduction Besides the proteinogenic β-hydroxy

• % yield) followed by acidic cleavage of the acetonide to yield building block 24 in 71% yield (Scheme 4). Acylation reactions were carried out with DIC as coupling reagent and catalytic amounts of DMAP. Based on this protocol, esterification reactions with octanoic acid (25) and 6-methylheptanoic acid (26

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• eventually obtained in high yields from benzoic acid using Steglich’s esterification [61] (Table 2, entry 3). With enal 9 in hands, selective hydrogenation of the C–C double bond had to be accomplished in the next step. Lipshutz’ modification [62] of Stryker’s reagent [63], which we had previously used

Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination

• Łukasz Górecki,
• Artur Mucha and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 883–889, doi:10.3762/bjoc.10.85

• , phosphorus compounds chemistry, particularity that avoiding an expansion of the core carbon skeleton [10][11][12][13], is poorly recognized and mainly involves esterification of different phosphorus acids with the O-9-hydroxy group [14][15][16][17][18][19][20][21]. These phosphorus esters were consecutively

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• p-xylene via consequtive iodination–oxidation–esterification reactions [32][33][34], followed by the final phosphanylation step that afforded linker 3 in excellent yield (Scheme 2b). Compounds 2 and 3 each displayed one signal in the 31P NMR spectrum at −3.5 and −3.8 ppm (Supporting Information File

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• . Selected recent synthetic work by us and others is presented below. Review Phospholes Several compounds have been prepared in this series. Keglevich and coworkers realized the synthesis of phosphole derivatives 2a–f based on the McCormack reaction [10] followed by microwave-assisted esterification of the

• 2 equivalents of cinnamyl alcohol 44 in the presence of 2 mol % of Pd/Xanthpos followed by an esterification using benzyl bromide. Ozonolysis, and reductive amination using excess benzylamine in the presence of sodium cyanoborohydride completed the synthesis. Phosphorines Two phosphorines 47a,b were

• reaction between bis(trimethylsiloxy)phosphine and the dibromide 50 followed by the esterification of the phosphinic acid using diazomethane (Scheme 21) [32]. The heterocyclization step followed methodology initially introduced by Frost et al [33]. Compound 51 was subsequently converted into the

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• diol 32a into macrocycle 34. Dihydroxylation of the macrocyclic olefin 34 to diol 35 and subsequent esterification to the bis-(R)-Mosher ester 36; (S)-MTPA-Cl = (S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl chloride. Calculated relative energy differences of the Z- and E-configured isomers of

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• carbon (two diastereomers) in the 13C NMR. Additionally, a short 3 step route to the functionalized glutamic and aspartic acid derived Weinreb amides 5e and 5f was coined as outlined in Scheme 3: At the outset both amino acids (1e and 1f) were subjected to esterification of the sterically less hindered

• side chain carboxyl function with acetyl chloride in MeOH [70][71][72]. Neutralization of the reaction mixture with K2CO3 and reductive benzylation [73] in one-pot then delivered the benzyl amines 8e and 8f. While glutamic acid showed selective mono esterification after 3 h at room temperature, the

• aspartic acid mono ester was obtained in a 5:1 ratio with the diester (not shown) after approximately 18 h of reaction time. Shorter reaction times in the esterification step of 1f decreased the yield of 8f. The amines 8e and 8f were converted in a straightforward manner to the carbamates 2e and 2f under

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• strategy and employed the Ireland variant of the Claisen rearrangement to construct the crucial C9–C10 bond (Scheme 4). In this strategy the A-ring 25 could be merged with the bicyclic C–D system 26 by esterification in order to obtain the allyl ester rearrangement precursor 24. Murai et al. [48] showed

• ). Esterification with cyclohexanecarboxylic acid gave the desired allyl ester 27. Furthermore, to investigate the influence of the protecting groups at C11, C12 and C14 on the stereoselectivity and reaction rate, the allyl esters 28, 29 and 30 were prepared. The four rearrangement precursors 27, 28, 29 and 30 were

• directing effect of the β-hydroxy group. Bicyclic system 65 could be obtained by ring-closing metathesis using Grubbs 1st generation catalyst and subsequent selective deprotection of the primary silyl ether. After esterification with 4-oxocyclohexanecarboxylic acid (25) and protection of the remaining two

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

• TMSCN [159][160][161], followed by protonation of the TMS-enolate and esterification of the intermediate acyl cyanide yielding allyl ester 191. This ester was transferred into the corresponding carboxylic acid, followed by formation of the acid chloride. The chloride was displaced with an azide, which

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• . The ΔδSR distribution model for a bisMTPA derivative of an acyclic 1,2-diol is shown in Figure 4. Thus, esterification of plakilactone G (1) with (−)- and (+)-MTPACl in pyridine led to bisMTPA derivatives which ΔδSR distribution is reported in Figure 4. The observed sign distribution model is

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• unified precursor of balanol (1) and an azepin ring-modified balanol 3. Derivative 4 could be obtained through esterification between the carboxylic acid 5 and the allylic alcohol 6. We thus focused on the synthesis of the two key fragments 5 and 6. The synthesis of the benzophenone unit has previously

• . The esterification of the allylic alcohol 29 with the acid 7 (Scheme 3) proceeded best in the presence of Mukaiyama’s reagent [66], 2-chloro-1-methylpyridinium iodide, to provide the ester 31 in 73% yield. Simultaneous hydrogenolytic removal of the O-benzyl groups and the N-Cbz group under reported

Triphenylene discotic liquid crystal trimers synthesized by Co₂(CO)₈-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition

• Bin Han,
• Ping Hu,
• Bi-Qin Wang,
• Carl Redshaw and
• Ke-Qing Zhao

Beilstein J. Org. Chem. 2013, 9, 2852–2861, doi:10.3762/bjoc.9.321

• (pentyloxy)triphenylene, according to a simplified one-pot method [52]. The undec-10-yn-1-yl p-toluenesulfonate was prepared by LiAlH4 reduction of the acid and tosylation of the alcohol [53][54]. Then monomers 2 and 3a–c were synthesized by the direct esterification or etherification reaction between phenol

Novel supramolecular affinity materials based on (−)-isosteviol as molecular templates

• Christina Lohoelter,
• Malte Brutschy,
• Daniel Lubczyk and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2013, 9, 2821–2833, doi:10.3762/bjoc.9.317

• , (−)-isosteviol can be oxidized under Riley conditions (Table 1, reaction conditions a: selenium dioxide/xylene) [62][63] to give the corresponding diketone 9 [66]. Subsequent esterification with 3,5-dinitrobenzylic chloride under basic conditions (Table 1, reaction conditions b for R = DNB) [67] proceeds with a

• carried out (Scheme 4). Again, both paths A and B lead to the formation of the desired PNB protected diketone 11. Esterification was achieved by reaction with 4-nitrobenzyl chloride and cesium carbonate in DMF (Table 1, reaction conditions b for R = PNB) [68]. Both sequences A and B proceed with similar

• triptycene 17 by condensation of 18 with hexaammoniumtriptycene hexachloride 4. Olefin metathesis of all-syn-17. Oxidation and esterification sequence of 1. Supporting Information Supporting Information File 500: Characterization data, spectra of synthesized compounds, QCM set up, and QCM screening details

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• ]. Another drawback of this route is the use of the toxic and carcinogenic iodomethane in the esterification reaction. Since the first synthesis of aldehyde (S)-1 by Garner there have been many modifications and improvements to the synthesis of the enantiomers ((R)-1 and (S)-1). Modifications to the original

• synthesis have focused either on the reaction sequence (esterification first and then Boc protection) or on the reduction to aldehyde. Other groups have tried to improve the synthesis of the aldehyde. McKillop et al. found that the esterification reaction is performed best first with 235 mol % of HCl