Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• to orthogonally protected amino acids 46 and 47 (Scheme 7) [58]. Installation of the C-2 stereocentre again began with Garner’s aldehyde 48 and Wittig olefination, followed by Sharpless dihydroxylation to stereoselectively afford diol 49 [59][60]. The C-2 epimer was accessed via Still–Gennari

• olefination of aldehyde 48 to afford the Z-olefin, which underwent dihydroxylation using potassium osmate to afford diol 50 [61][62]. With both diastereomers in hand, conversion to protected amino acids 46 and 47 was effected in four steps. With amino acids 46 and 47 in hand, conversion to the corresponding

• with isothiourea 33 followed by mesyl chloride afforded cyclic guanidine 72 in 70% yield. Silyl deprotection, Swern oxidation and Still–Gennari olefination afforded Z-alkene 73. Diastereoselective dihydroxylation of 73 followed by treatment with 1,1'-thiocarbonyldiimidazole (TCDI) and sodium azide

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• the key step (right, Scheme 8) [79]. After reduction of the ester 26, a Sharpless asymmetric dihydroxylation (AD) [86][87][88] reaction furnished diol 31 with a high degree of both regio- and enantioselectivity. Osmium-promoted oxidative type B cyclization of 31 proceeded in high yield (81%) and with

• succeeded in synthesizing cis-solamin A (29) utilizing a ruthenium tetroxide-catalyzed type A oxidative cyclization approach (Scheme 9) [80]. Silyl-protected dienediol 34, the oxidative cyclization precursor, was synthesized from all-trans-cyclododecatriene 33 in four steps including dihydroxylation, glycol

• , polyketides, amino acids, fatty acids as well as acetogenins and terpenoids) are summarized in this review article. Putative structures of geraniol 1a (R = H) or 1b (R = H) (in 1924), their expected dihydroxylation products 2a or 2b and the true structure 3 as determined by Klein and Rojahn in 1965 [8

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

• ] (Scheme 2). Selective protection of the C5 primary hydroxy group as PMP ether using p-methoxyphenol under Mitsunobu reaction conditions afforded 4 that on benzylation of the C3 hydroxy group (NaH and benzyl bromide in DMF) gave compound 5. Upjohn dihydroxylation of 5 using K2OsO4·2H2O followed by

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

• correlations and vicinal coupling constants as shown in Scheme 7. For further conversion to key intermediates 3 and 4, the tosyl groups of 42 and 43 were removed with SmI2 [54][55] giving the free amides 44 and 45. The terminal double bonds were then oxidized by dihydroxylation with OsO4 and periodate cleavage

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

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• encompass asymmetric dihydroxylation of trans-methyl cinnamate or cinnamyl alcohol [6], chiral azetidin-2,3-dione [7], asymmetric C–H amination reactions of a prochiral sulfamate [8], oxazaborolidine reduction of 3-chloropropiophenone or ketone [9], and an imidazolidin-2-one chiral auxiliary mediated

Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism

• David Porter,
• Belinda M.-L. Poon and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 2549–2556, doi:10.3762/bjoc.11.275

• ) are established catalysts of C–O bond formation, oxidising hydrocarbon substrates via hydroxylation, epoxidation and dihydroxylation pathways. Herein we report the capacity of these catalysts to promote C–N bond formation, via allylic amination of alkenes. The combination of N-Boc-hydroxylamine with

• intermediate. Conclusion FeTPA (4) and FeBPMEN (5) are established catalysts for the hydroxylation, dihydroxylation and epoxidation of hydrocarbon substrates [48][58][59][60]. In this study we have shown that they can also catalyse the allylic hydroxyamination of alkenes with N-Boc-hydroxylamine. Mechanistic

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Synthesis of novel N-cyclopentenyl-lactams using the Aubé reaction

• Madhuri V. Shinde,
• Rohini S. Ople,
• Ekta Sangtani,
• Rajesh Gonnade and
• D. Srinivasa Reddy

Beilstein J. Org. Chem. 2015, 11, 1060–1067, doi:10.3762/bjoc.11.119

• cyclopentenyl-substituted lactams. Upon dihydroxylation, this affords the N-cyclopentenyl-lactam compounds in racemic form. Given the numerous uses of nucleosides and related compounds, we were interested in the synthesis of carbocylic nucleoside mimics. The attempts and results are described herein. Keywords

• corresponding triols (±)-11 to (±)-15 were readily formed and obtained as single diastereoisomers, indicating that the reaction proceeded in a highly selective manner. The triols (±)-14 and (±)-15 also resulted from corresponding substituted lactams. The observed selectivity of the dihydroxylation can be

• + Na]+: 232.1308, found 232.1316. General procedure for the dihydroxylation reaction 0.2 mL of OsO4 (2.5% in tert-butanol, 1 mol %) was added to a solution of cyclic lactam (0.27 mmol) and NMO (0.3 mmol, 1.1 equiv) in tert-butanol at room temperature and stirred for 2–5 hours. Upon completion of the

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• (Z-Cl) afforded protected amino ester (±)-3 in 78% yield. In agreement with our earlier observations [40][41][42] C–C double bond functionalization of the cyclooctene β-amino ester via dihydroxylation with N-methyl morpholine N-oxide (NMO) in the presence of OsO4 afforded the corresponding all-cis

• dihydroxylated ethyl β-aminocyclooctanecarboxylate (±)-4 in 90% yield (for dihydroxylation, see also reference [54]) (Scheme 2). Amino ester (±)-4 was next subjected through its vicinal diol moiety to oxidative ring opening with NaIO4 in MeOH at 20 °C, which resulted (monitored by TLC) in the corresponding ring

• chromatography. Dihydroxylation of (±)-7 with NMO/OsO4 next afforded an oily mixture of cis and trans dihydroxylated cyclooctane β-amino esters (diastereomeric mixture of (±)-8) in 77% overall yield after column chromatography. Our attempts to separate this nearly 1:1 mixture of the two dihydroxylated

Photovoltaic-driven organic electrosynthesis and efforts toward more sustainable oxidation reactions

• Bichlien H. Nguyen,
• Robert J. Perkins,
• Jake A. Smith and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2015, 11, 280–287, doi:10.3762/bjoc.11.32

• reason, the sunlight-driven oxidation reactions were extended to the recycling of chemical oxidants. Three examples are shown in Scheme 4 [12] where each was chosen for its unique feature related to the indirect electrochemical approach. In the first reaction (Scheme 4a), an asymmetric dihydroxylation

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• product 19. Dihydroxylation of 19, followed by oxidative cleavage of the resultant diol gave aldehyde 20 in 80% yield over two steps. Addition of lithiate 16 to aldehyde 20 gave alcohol 21 in 87% yield as an inseparable 1:1 mixture of diastereoisomers. Hydrogenolysis of the benzyl ether in 21 gave ketal

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• from a common intermediate which featured a highly selective dihydroxylation reaction and a RCM reaction as key steps. Keywords: chiral pool; dihydroxylation; indolizidines; quinolizidine; ring-closing metathesis; Introduction Polyhydroxylated indolizidine derivatives have attracted continued

• . Having secured quick access to the unsaturated indolizidinone and quinolizidinone ring systems 10 and 12, we considered their conversion to the desired polyhydroxylated targets through dihydroxylation of the double bond. Pleasingly, dihydroxylation of compound 10 proceeded well under Upjohn conditions

• [35] and provided a single isomer 13 (Scheme 2) in high yield (96%). The high selectivity in the dihydroxylation step is noteworthy as in similar situations mixture of diastereomers has occasionally been formed [36][37]. The stereochemical identity of the newly formed stereogenic centres in 13 could

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• groups of the previously prepared diol 33, followed by OsO4 dihydroxylation of the C–C double bond provided the corresponding diol in good yield. The resulting vicinal diol was then cleaved by sodium periodate to the corresponding aldehyde, which was immediately subjected to a Horner–Wadsworth–Emmons

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• introduced the two hydroxy groups trans- to the amine moiety using an Upjohn dihydroxylation. Freshly-prepared aqueous OsO4 stock solutions were required to obtain good yields in this step. The reaction proceeded smoothly and the 1H NMR spectra of the crude reaction mixture showed a 96:4 ratio of cis- to

• following syn-dihydroxylation. Using the Upjohn conditions previously described we obtained the desired triol 18 in good yield and excellent diastereoselectivity (>99% by 1H NMR after column chromatography) [30]. Tri-benzoate 19 was subsequently obtained in good yield using the standard benzoylation

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• circular dichroism spectroscopy (CD) using the in situ dimolybdenum methodology (see next chapter). Next steps of the synthesis consisted of the protection of the C6–OH as benzyl ether (to 12) and osmylation of the double bond. The cis-dihydroxylation provided, as single stereoisomer, a diol to which

• glucose-rings were connected via an enone linker. The dimer was then converted into a (partially protected) triol via a stereoselective reduction of the carbonyl group and highly selective cis-dihydroxylation of the double bond. The configuration at each new stereogenic center was determined by CD

• , 70.2 (C-1'), 69.9, 66.7 (C-6'), 65.6 (C-6'), 27.0 (t-Bu), 26.9 (t-Bu), 19.3 (CH3), 19.3 (CH3); anal. calcd for C148H156O21Si2 (2327.05): C, 76.39; H, 6.76; found: C, 76.44; H, 6.73. Dihydroxylation of the double bond of 12. Olefin 12 (60 mg, 0.026 mmol) and OsO4 (30 mg, 0.120 mmol) were dissolved in

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• sequence, which incorporates a regioselective pyrrole alkylation, an electrophilic aromatic nitration and a regio- and stereoselective Corey–Noe–Lin dihydroxylation [18], has previously been described (in the total synthesis of heronapyrrole C) [3]. The procedure of Shi et al. [19][20][21] was then used to

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• -groups to olefinic acid by either asymmetric epoxidation, dihydroxylation or aminohydroxylation [10][11][12][13][14][15], (ii) the asymmetric synthesis of β-lactams by a Staudinger reaction between ketene and imine to give the corresponding amino acids [16], and (iii) the Lewis acid catalyzed

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

• potassium osmate/NMO to obtain the vicinal diol 35 in 76% yield (Scheme 8). In the case of a Z-configured olefin 34 this dihydroxylation should give a cis-configured diol (meso compound), whereas an E-configured olefin 34 would lead to a racemic mixture of the corresponding trans-configured diol. However

• 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

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• starting from aryl(trifluoromethyl)ketone 19 (Scheme 3), which itself was synthesized via Grignard monoallylation of 1,4-dibromobenzene, followed by dihydroxylation, dioxolane protection and trifluoroacetylation of the remaining brominated position [16]. Refluxing of ketone 19 with NH2OH·HCl in pyridine

Efficient carbon-Ferrier rearrangement on glycals mediated by ceric ammonium nitrate: Application to the synthesis of 2-deoxy-2-amino-C-glycoside

• Alafia A. Ansari,
• Y. Suman Reddy and
• Yashwant D. Vankar

Beilstein J. Org. Chem. 2014, 10, 300–306, doi:10.3762/bjoc.10.27

• δ 4.00, which in turn was adjacent to the amide proton at δ 4.85, thereby indicating that the amide moiety is present at the C-2 position (see Supporting Information File 1). The internal olefin was subjected to a dihydroxylation under the Upjohn conditions [64], followed by an acetonide protection

• rearrangement took place from the axial side, as expected, since the hydroxy group at C-4 is axially oriented in compound 9. Moreover, the dihydroxylation took place from the side opposite to the amino group at C-2, which can be attributed to the steric hindrance from the bulky amide group. A D-galacto

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• interesting option is the pathway via oxepines [15][16][17][18] and the subsequent dihydroxylation or direct reduction of their C=C double bond to give the corresponding oxepane derivatives [19][20]. Alternatively, oxepanes were also synthesized by the ring enlargement of their six-membered homologues [21][22

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

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

• possible synthesis of an azepane ring-modified balanol derivative along the projected pathway. To this end, dihydroxylation of the adduct 31 was next attempted. Pleasingly, the dihydroxylation of 31 proceeded smoothly; however, unfortunately to provide an inseparable mixture of the two possible

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• C7 stereochemistry was introduced via asymmetric dihydroxylation [25][26]. Thus, ester 13 [27] was treated with AD-mix-α in t-BuOH/H2O to give diol 14 in reasonable yield. The enantioselectivity and absolute configuration of the secondary alcohol was determined by conversion of diol into the bis-(S