Solvent-free synthesis of novel para-menthane-3,8-diol ester derivatives from citronellal using a polymer-supported scandium triflate catalyst

• Lubabalo Mafu,
• Ben Zeelie and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 2046–2054, doi:10.3762/bjoc.12.193

• environmentally friendly method for the synthesis of para-menthane-3,8-diol from natural citronellal oil in 96% yield, under solvent free aqueous conditions. The acylation of para-menthane-3,8-diol with various acid anhydrides over polymer-supported scandium triflate (PS-Sc(OTf)3) catalyst was subsequently

• developed, where both hydroxy groups of para-menthane-3,8-diol could be simultaneous acylated under mild reaction conditions to form the corresponding diesters in good yields. The advantages of this method include a simple procedure from natural resources, using solvent-free reaction conditions. Keywords

• : acylation; diesters; para-menthane-3,8-diol; PS-Sc(OTf)3; Introduction Although South Africa has a substantial petrochemical industry, the fine chemical industry is very small and most chemicals are imported. As such there is significant interest in the use of natural resources for the manufacture of added

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• 32 of each of these kinetic resolutions had the same absolute configuration. Combining these two complementary catalysts leads to a highly efficient parallel process wherein each catalyst enantioselectively hydrolyzes one enantiomer of the epoxide, ultimately forming diol (R)-32 in 92% yield with 89

• % ee [36]. An especially remarkable example of type III enantioconvergent catalysis utilizes a single enzymatic catalyst. Faber observed that Nocardia EH1 is capable of catalyzing the hydrolysis of racemic epoxide 33 to the corresponding diol (2R,3R)-34 in 79% chemical yield with 91% ee (Scheme 8) [37

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• asymmetric cycloaddition of the silylated diene 145 to the acylnitroso compound 144 (Scheme 28). The first step of the synthesis of cis-1,3-diamino-1,3-dideoxycyclitols 149 starts with an asymmetric hetero-Diels–Alder reaction of O-isopropylidene-protected cis-cyclohexa-3,5-diene-1,2-diol 147 with (−)-2,3

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• -glucose derived alcohol 3 in 13 steps and 14% overall yield. Thus, the Sharpless asymmetric epoxidation of allyl alcohol 7 followed by trimethyl borate mediated regio-selective oxirane ring opening with azide, afforded azido diol 10. The acid-catalyzed 1,2-acetonide ring opening in 10 concomitantly led to

• -dioxabicyclo[3.2.1]octane A could be glycosylated stereoselectively with the requisite nucleobase to give β-nucleoside pyranosyl skeleton 2. The bridged bicyclic system A was visualized from the azido diol B. Thus, hydrolysis of the 1,2-acetonide functionality in B will lead to in situ generation of

• oxidative cleavage of diol with silica-supported NaIO4 gave aldehyde that was directly reacted with ethyl 2-(triphenylphosphoranylidene)acetate to give α,β-unsaturated ester 6 (E/Z = 92:8) in 83% yield over three steps. Reduction of ester 6 (E-isomer) with DIBAL-H gave allyl alcohol 7 – a synthone for the

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• and solid support for the automated solid-phase synthesis of S. pneumoniae serotype 3 CPS structures. HPLC chromatogram of the crude products of the attempted AGA of SP3 trisaccharide 5; conditions: YMC Diol 300, H/EtOAc, 0% EtOAc (5 min) to 55% EtOAc (70 min), ELSD. HPLC chromatogram of the crude

• products of the attempted AGA of SP3 trisaccharide 9; conditions: YMC Diol 300, H/EtOAc, 0% EtOAc (5 min) to 70% EtOAc (70 min), ELSD. HPLC chromatogram of the crude products of the automated solid-phase SP3 trisaccharide 5 synthesis; conditions: YMC Diol 300, H/EtOAc, 0% EtOAc (5 min) to 60% EtOAc (60 min

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• alcohol 18 (15%) and diol 17 (20%). This result could not by improved using reverse addition conditions (Scheme 2). Therefore, selective monoprotection of the dialdehyde 5 was next attempted. Unfortunately, treatment of the latter either with ethylene glycol or 2,2-dimethylpropandiol gave a mixture of di

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• substrate 14 was prepared from amine 12 by cross-metathesis with 2-butene-1,4-diol (13) in the presence of Grubbs-II catalyst 21. However, in the subsequent coupling reactions of 14 with TsNCO it became apparent that this homoallylic amine was too unreactive to enable a double addition to access 15 directly

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• dihydroxylation [24] afforded the inseparable (flash chromatography) (±)-3-methylbut-3-ene-1,2-diol (rac-17) and (±)-2-methylbut-3-ene-1,2-diol (rac-18) in a 3:2 ratio and unoptimized 67% yield (Scheme 3). Investigating O-nitrate ester formation the rac-17/rac-18 mixture was dissolved in dichloromethane

• 65% yield. Subsequent reaction of 21 with methyllithium (2.5 equiv, −78 °C, THF) in an alkylative double ring-opening process afforded, exclusively, (±)-3-methylbut-3-ene-1,2-diol (rac-17) in a 54% yield (Scheme 4). The next step required the mild regioselective O-nitration of rac-17. Olah et al

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• efficient platforms for bidentate coordination in metal catalysis and good precursors of carboxylic acids, ketones and aldehydes upon oxidative cleavage of the keto/diol moiety [72]. More recently, a comprehensive study on the first evidence of the utility of these acceptors in organocatalysis has been

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• achieved by using chiral column chromatography (Chiralpak AD, Daicel) followed by recrystallization from H2O/MeOH (1:4) providing the appropriate crystal for X-ray analysis. Accordingly, the enantiopure crystal of 5a was unambiguously assigned to a tetrahydro-2H-pyran-2,4-diol structure with all phenyl and

• all. The only acyclic aliphatic ketone that led to the formation of the domino aldol product was pinacolone (1d), which gave the tetrahydro-2H-pyran-2,4-diol 7d in 20% yield (Scheme 3, Table 6). The reactions of the cyclic ketones were only successful in the case of cyclohexanone (1h), while

• formation of the metal-bound tetrahydro-2H-pyran-2,4-diol. Under thermodynamic control all large substituents R (methyl, phenyl) are placed in the equatorial position which leads for all metal ions excluding Ga to only 1 out of 16 possible diastereoisomers. To shed more light on the mechanism, DFT

A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• -fluorohexahydro-2H-chromenes under the developed conditions, the reaction occurs with inversion of configuration. Keywords: chirality; fluorine; halo-Prins reaction; isopulegol; monoterpene; Introduction Recently, we have found that a reaction between para-mentha-6,8-dien-2,3-diol (1) and aromatic aldehydes in

• para-mentha-6,8-dien-2,3-diol (1) with 3,4,5-trimethoxybenzaldehyde (6a) in the presence of BF3·Et2O was chosen as a model reaction. The study was started with the investigation of the effect of the reaction conditions and the reactant ratio on the yield of a fluorinated product (Table 1). The addition

• their double bond position isomers in the reaction mixtures. In this study, we did not seek to isolate the individual byproducts. Compounds 2a and 8a produced by a reaction of diol 1 with aldehyde 6a are formed as a mixture of diastereomers differing in the position of substituents at the C(5) carbon

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• nitroalkenes and commercially available 1,4-dithiane-2,5-diol to 3,4,5-substituted tetrahydrothiophenes, bearing a quaternary stereocenter, is presented. A secondary amine thiourea derived from (R,R)-1,2-diphenylethylamine was found to be the most effective catalyst when using trans-β-methyl-β-nitrostyrenes

• report on a dynamic system combining a 1,1,3,3-tetramethylguanidine (TMG)/ZnI2-catalyzed diastereoselective cascade sulfa-Michael/nitroaldol reaction followed by lipases catalyzed kinetic resolution using two representative trans-β-methyl-β-nitrostyrenes and 1,4-dithiane-2,5-diol as reagents [21]. One

• [22] with 1,4-dithiane-2,5-diol. Based on all above considerations and prompted by our interest in asymmetric synthesis of functionalized tetrahydrothiophenes [14], we wondered whether we could use bifunctional organocatalysts to develop a diastereo- and enantioselective cascade sulfa-Michael

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• at δ 111.7 ppm in the 13C NMR spectrum. The Michael acceptor 13 was prepared according to the literature procedure starting from cyclohex-3-enecarbaldehyde (25) [38]. The diol 26 was oxidized with activated MnO2, leading to selective oxidation of the secondary alcohol forming 27 in 83% yield. The

• lactol 34 with methylmagnesium bromide afforded diol 35 in 72% yield. Selective oxidation of the allylic alcohol group in 35 with MnO2, followed by acetylation of the secondary hydroxy group with acetyl chloride, triethylamine and DMAP furnished cyclohexenone 36 (Scheme 5). The Hauser annulation of

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• , diastereoselective reduction of the cross-benzoin products with NaBH4 afforded valuable syn-diol products. Goodman and Johnson disclosed a dynamic kinetic resolution of β-halo-α-ketoesters via NHC-catalysed asymmetric cross-benzoin reaction. Here, the cross-benzoin reaction of aromatic aldehydes with β-stereogenic-α

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• acid spontaneously self-assemble to quantitatively form a stable complex. Interestingly, when the chirality of the binol or amine was fixed the 1H NMR of the complexes formed using a scalemic mixture of the other chiral partner (diol or amine) results in a 1H NMR where signals due to both

• diastereomeric complexes are clearly separated. The diastereomeric imine signals are particularly useful since they are in a region of the spectra clear of interference from signals due to the binol (diol) or amine. Integration of the pair of imine signals provides a diastereomeric ratio which can be related to

• the enantiomeric excess of the original scalemic mixture of binol (diol) or amine (Figure 15). The three-component system was very versatile and we could use the complexes to determine the enantiomeric excess (ee) of amines [69][70], diamines [71], amino alcohols [72], hydroxylamines [73] and diols

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• of DIBAL-H to produce 2A,3B-diol 46 from TRIMEB (Scheme 9) [90]. The two remaining free alcohols were then functionalized with the α-nucleophile and an imidazole group [88]. The acid–base dyad thus obtained is likely to improve the hydrolysis of nerve agents. The imidazole group was first introduced

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• , Table 2) were obtained in high and very high yields. Alkenes were converted almost quantitatively and the excess of (Z)-but-2-ene-1,4-diol diacetate was recovered. Some side products of self-metathesis (SM) of terminal alkenes were isolated. It should be added that two terminal olefins (entry 4, Table 2

• ) gave also SM products besides the desired CM products. Furthermore, more dimeric products gave allyloxybenzene than hex-5-enyl acetate. It is worth noting that the CM reaction between styrene and (Z)-but-2-ene-1,4-diol diacetate (entry 1, Table 2) was highly efficient (97% yield) using catalyst 9

Genicunolide A, B and C: three new triterpenoids from Euphorbia geniculata

• Alia Farozi,
• Javid A. Banday and
• Shakeel A. Shah

Beilstein J. Org. Chem. 2015, 11, 2707–2712, doi:10.3762/bjoc.11.291

• -ene-5,8-lanostadiene-3β-ol, 3β,24S,25-trihydroxycycloartane, 3β,24(R),25-trihydroxy-cycloartane, 24-methylenecycloartan-3β-ol [16], cycloart-23-ene-3,5-diol [17], lupeol, lupeol acetate, ginnone, ambrein, lupeone [18], 24-methylenecycloartanol [19], cycloart-25-en-3β,24-diol [20] and cycloart-22-ene

• -3β,25-diol [21]. In addition, nor-isoprenoids and coumarins have also been reported from few species of Euphorbia [22][23][24]. Euphorbia geniculata Orteg. [25][26], is a wild weed found in the Jammu region of India [27]. The plant is locally used for the treatment of bacterial infections and

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• benzylic bromination followed by elongation of the C3 unit [22]. To this end, the ester group at the C1 position of 15 was reduced by lithium borohydride, and the resultant 1,3-diol protected to give acetal 16 [16]. After various experiments, selective bromination of the methyl group on the aromatic ring

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• strands, which are expected to push the esterification towards quantitative conversion. Compound 5 combines side-chain cis-diol functionality for boronic ester formation and the potential of controlled oligomerization by peptide chemistry. Azido ester 5 is a precursor of the dipeptide Hot=Tap, which

• serves as a β-turn mimic in peptides and proteins [24][25][26]. Alternatively, Fmoc-Hot=Tap-OH (8, Figure 5) is available for oligomerization on SPPS to templates of adjustable length with a systematic increase of the number of cis-diol functions assembled on a rigid peptide backbone. In solution

• -membered (triangle, 3) esters. The overlapping resonances in the 1H NMR spectra of the esters in the region between 4 and 5 ppm are resolved in the HSQC spectrum, where the alpha-carbons are visible below 50 ppm and the CH–OB groups between 65 and 80 ppm. Diol 5 (6.08 mg, 20.0 μmol, 1.0 equiv) and 3

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• stereogenic centers, derived from tartaric acid, giving the product as a single isomer in good yield (Scheme 11). Sugimura et al. [31] expanded this method by introducing chiral 1,3-diol-derived tethers into the substrates, delivering the corresponding coupling products in excellent diastereoselectivity

• -permethyl-tellimagrandin I. Total synthesis of (+)-gossypol. Total synthesis of (−)-mastigophorene A. Total synthesis of isokotanin. Synthesis of dimethyl[7]thiaheterohelicenes. Intramolecular coupling with chiral ortho-substituents. Chiral 1,3-diol-derived tethers in the diastereoselective synthesis of

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• highest activity. In 2010, Nandurdikar et al. linked the two (or four) molecules of NO donor prodrugs together through the triazole spacers [22], which has potential application as NO-releasing materials. They first prepared the benzylidene-protected 2,2-di(azidomethyl)propane-1,3-diol containing the

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• conditions [48] and an ensuing desilylation furnished a diol. In order to introduce a leaving group for the following key step, the secondary hydroxy group was tosylated to afford 79. Once again, a stereospecific Grob fragmentation of tosylate 79 served as the key step for the synthesis of the

• commenced with the preparation of diol 96 by a palladium-catalyzed hydrostannylation of 2-butyne-1,4-diol (95). Regioselective silylation with tert-butyldimethylsilyl chloride of the sterically less hindered alcohol, iodination and silylation of the primary alcohol with trimethylsilyl chloride gave vinyl

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• epoxidation of 5 with tert-butylhydroperoxide (TBHP) in toluene gave 6 ([α]D +34.2° (c 1.3, CHCl3)) in 95% yield [9][22]. Then, the diol 7 was obtained in 85% yield from the reduction of epoxide 6 with LiAlH4 in THF at 0 °C. The diol 7 was easily purified by crystallization (85% yield, n-hexane at −50 °C up