Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• chiral HPLC analysis of major diastereomer. The dr values were determined by 1H NMR analysis. Method A: with 10 mol % of d as a catalyst, −20 °C, 12 h. Method B: with 10 mol % of d as a catalyst, −10 °C, 24 h. A plausible mechanism. Optimization for the reaction conditionsa. Supporting Information

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• ], and aryl thiols [75][76] can be formed in moderate to quantitative yield with the 1,2-trans diastereomer prevailing in all instances (Scheme 23) (also partially reviewed in Noguchi et al. [70]). The substrate scope was extensive in all instances and included successful glycosylation of up to

• to provide the 1,2-trans β-diastereomer. Only in pathway A, by direct nucleophilic displacement of the β-activated complex, does the minor α-diastereomer form. To demonstrate the potential utility of this methodology in labeling strategies, the Shoda group has also accessed fluorescent thioglycosides

• -alkynyl acceptors) or Et3SiH (alkynyl acceptors). In all cases the yields were very good and the stereoselectivity pretty good for the 1,2-cis glycoside diastereomer. The mechanism is thought to proceed through an initial hydrogenolysis of the benzyl groups to produce a reactive dihydroxytriazinyl

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• coupling, acetate protection of the newly generated hydroxy group and DBU-mediated elimination. This three-step sequence proceeded as shown in Scheme 6 with excellent yields (94%) giving the triene 33 as a single diastereomer, which demonstrates the usefulness of aldol condensations in complex target

• alcohol 60. In this Δ5,6-trans-selective reaction the desired anti-diastereomer could be isolated in 85% with a dr of 6:1, which presumably arises from a chelation-controlled stereoselectivity [89]. The aldehyde 59 itself can be prepared in two steps from the corresponding Roche ester [90]. After

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• yield was 52% in three steps and the product purity was excellent. Two key diastereomers were prepared with efficient and direct access to the α-C-arylglucoside. Keywords: arylzinc derivative; β-C-arylglucoside; diastereomer impurity; ipragliflozin L-proline; stereoselective synthesis; Introduction

• was purified by recrystallization from methanol, and the desired product in 65.3% yield with HPLC purity 99.79% was obtained; the diastereomer 5’ was not detected. The protecting groups of 5 were removed in presence of sodium methoxide in refluxing methanol, and then recrystallized to give

• , 115.7, 73.1, 70.6, 68.4, 62.1, 38.7, 30.0, 27.0; MS (ES+) m/z: 763.44 [M + Na]+. Structure of ipragliflozin L-proline. Stereoselective synthesis of C-aryl glycoside by Lemarie. Stereoselective synthesis of β-C-arylglucoside 5. Synthesis of 1. Synthesis of diastereomer 6’ and 5’. Conditions for the

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• nucleophilic group were appended to the para-quinol, it would be possible to construct a 5–6–5 fused ring system. Indeed, when R = CH2CH2NHBoc (1f), the desired tricyclic product 2f was obtained. In all cases only a single diastereomer was observed. In a substrate where a β-methyl group is present on the

• desymmetrizing intramolecular conjugate addition of a tethered dithiane moiety to para-cresol-derived cyclohexadienones. The substrates are easily accessible from cheap starting materials and the reaction provides functionalized bicyclic lactones as a single diastereomer. The products of the reaction were able

Unpredictable cycloisomerization of 1,11-dien-6-ynes by a common cobalt catalyst

• Abdusalom A. Suleymanov,
• Dmitry V. Vasilyev,
• Valentin V. Novikov,
• Yulia V. Nelyubina and
• Dmitry S. Perekalin

Beilstein J. Org. Chem. 2017, 13, 639–643, doi:10.3762/bjoc.13.62

• diastereomer, however, it was not possible to unambiguously determine whether it was the cis- or the trans-isomer by NMR (including various correlation techniques) because of the high symmetry of both possible isomers. Attempts to grow crystals of 2c or its Br2 adduct for X-ray crystallography were also

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• 21–25 in 22–69% yield of two diastereomers, whereby one of the two diastereomers was formed in 5–65% diastereomeric excess (Scheme 3). Because of the low diastereomeric excess for compounds 21 and 22, the configuration of the major diastereomer was not determined. The configurations for the major

• diastereomers of 23–25 were obtained from crystal structure analyses and the correlation of the 13C NMR data. According to an X-ray analysis the minor diastereomer 23b has the configuration (S) at the new formed stereogenic center (Figure 2) [23]. The configuration of the new stereogenic centers in compounds 24

• and 25 were assigned on the basis of a characteristic down field shift in the 13C NMR of the carbonyl and the methine carbon atom in the major diastereomer (Table 1). The higher diastereomeric excess in compounds 24 and 25 obtained with 8-phenylmenthol (3) as auxiliary is attributed to an electronic

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• preference for the incorrect peptide diastereomer under specific conditions [12]. These results provide hints of more stringent substrate specificity at later stages of the GPA cyclisation cascade and we hence investigated StaF activity against altered peptide substrates, including pekiskomycin- (Pek) and

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• products 12b–d were obtained as racemic mixtures of diastereomers in which, as expected, the major diastereomer resulted from cis addition of hydrogen across the double bond. This was confirmed in the case of the reduced ester 12b, which was obtained in a good yield of 72% and a diastereomeric ratio of 85

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

• on the stereoselective formation of aziridine 27. This key reaction proceeded from allylglycine 28 in 28% yield to give a 7:3 mixture in favour of the S,S diastereomer. Attempted optimisation of the yield and diastereoselectivity afforded no improvement. The synthesis continued with aziridine opening

• protection, afforded protected β-hydroxyenduracididine 40. Alternatively, formation of epoxide 45 provided access to diastereomer 41. Synthesis of β-hydroxyenduracididine by Oberthür et al.: In 2014, Oberthür et al. reported a second generation synthesis of β-hydroxyenduracididine using a more concise route

• 75. Coupling of 75 with amino sugar 76 and global deprotection afforded minosaminomycin (9) in three steps from enduracididine (1). It should be noted that the diastereomer (2R-isomer) of 9 was also synthesised starting from D-enduracididine. Biological testing of both compounds revealed that the 2R

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• diastereomer is obtained in good to high yields, although multiple (five) stereocenters are present in products 4. The possible approaches of the azomethine ylide are shown in Figure 8. The X-ray diffraction structures of 4c, 4e, and 4r reflect that the cycloaddition proceeds via an exo-transition state

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• , and MeCN as a solvent, the three-component reaction for 2a was completed under microwave heating at 115 °C for 25 min. Without work-up, the reaction mixture was directly reacted with 1.0 equiv of N-benzylmaleimide (6a) under microwave heating at 125 °C for 25 min to give 7a as a major diastereomer of

• a denitrogenation compound in 74% LC yield with a 39:1 dr (Table 1, entry 5). The diastereomer 7a was isolated in 65% yield by preparative chromatography. The stereochemistry of the final product was established during the first [3 + 2] cycloaddition of the azomethine ylide which has been well

• column to afford purified product 7 as a single diastereomer. General procedure for [5 + 1] annulation for the synthesis of products 1 To a solution of compound 7 (0.5 mmol), in 1.0 mL of 1,4-dioxane was added formaldehyde solution (16% in H2O, 1.5 mmol). The reaction mixture was heated at 110 °C for 3 h

Silica-supported sulfonic acids as recyclable catalyst for esterification of levulinic acid with stoichiometric amounts of alcohols

• Raimondo Maggi,
• N. Raveendran Shiju,
• Veronica Santacroce,
• Giovanni Maestri,
• Franca Bigi and
• Gadi Rothenberg

Beilstein J. Org. Chem. 2016, 12, 2173–2180, doi:10.3762/bjoc.12.207

• alcohols as isopropanol and L-menthol. Despite their increased steric hindrance, very good results were obtained with a selectivity towards 3 >99% (Table 5; entries 3 and 4, 59 and 76% yield). In particular, it is important to underline that a single diastereomer of product 3d was formed (Table 4, entry 4

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

• diastereomer using a highly efficient and stereocontrolled synthetic strategy to construct the desired bis-THF ring building block 73 in two steps (Scheme 15) [120][121]. Thus, starting from commercially available trans-1,5,9-decatriene (71) a stereo- and positionselective Sharpless AD reaction [86][87][88

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• aryl moieties to design the rare pyran-4-carboxamide molecules. Moreover, during the regio- and diastereoselective transformation a quasi-hydrolysis of only one of the cyano groups had occurred. As a result only one diastereomer of 3,4-dihydro-2H-pyran-4-carboxamides 2 was obtained (Table 1). The

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

• -diene (120) with the acylnitroso dienophile 119 (Scheme 24) [10]. The reaction proceeded in 81% overall yield with a major cycloadduct 121 and minor diastereomer 122, with 98% de. The absolute configuration of the major cycloadduct was confirmed by an independent synthesis from the known bicyclic (1R,4S

• chiral acylnitroso dienophiles 133d and 133e with cyclohexadiene [107] and cyclopentadiene [117]. However, it is interesting that both groups showed that the dominant diastereomer could be altered based on the stereochemistry of the attached pyrrolidine. The imidazolidin-2-one auxiliary 133g was also

• of 3.3:1 with its diastereomer, not shown) in 45–50% overall yield. The camphor-derived nitroso agents 140a–d have also been used with great success in hetero-Diels–Alder reactions (Table 5). The sultam 140a gave the products with high stereoselectivity when reacted with both cyclopentadiene and

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

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• ester-activated N-Boc-valine to obtain compound 8 (Scheme 1). Treatment with DIBAL-H led to the reduction of both the ester and the CO group of the valine moiety (9). Compound 9 was obtained as a 9:1 mixture of diastereomers, the syn (S,S) diastereomer being the major one. The selectivity of the

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• recrystallization, over 100 mg of 1 was isolated as a single diastereomer and constitutional isomer, culminating a 9-step route with an overall yield of 21.8%. Conclusion In conclusion, a new protocol for the catalytic enantioselective bromochlorination reaction has been developed which has enabled the highly

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• due to the minimization of the A[1][3] interaction. Therefore, it is observed 3a’ produced from corresponding 8a’ as the major diastereomer whereas 3a” as minor one. Conclusion We have developed a cooperative catalytic strategy for highly regio- and enantioselective [3 + 2] cycloaddition reactions of

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• ketones 3–6 that led to tricyclic compounds. Methyl ketone 1 provided under the reaction conditions (2 mol % Pd(PPh3)4, 3.5 equivalents NEt3, DMF, 110 °C, 3 d) that had been optimized with compound 4 a moderate yield of the tetralin derivative 7 formed as a single diastereomer (Scheme 3). Although the

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• er) (Scheme 23b) [46]. This enantioselective addition process could be applied to a racemic mixture of axially chiral N-(2-tert-butylphenyl)itaconimide (98), furnishing atropisomers 99a and 99b as a stable and separable 1:1 mixture. A higher enantioselectivity was observed for the anti-diastereomer

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene

• Rudolf Knorr,
• David S. Stephenson,
• Ernst Lattke,
• Petra Böhrer and
• Jakob Ruhdorfer

Beilstein J. Org. Chem. 2016, 12, 1178–1184, doi:10.3762/bjoc.12.113

• -dibromo-1,1-dimethylindanes violate the rule by means of their values of 3J(cis) = 6.1 Hz and 3J(trans) = 8.4 Hz. The stereoselective formation of the trans diastereomer from 1,1-dimethylindene was improved with the tribromide anion (Br3−) as the brominating agent in place of elemental bromine; the

• established [1][2][3]. With indene as a cyclic olefin, the major product trans-1,2-dibromoindane was formed through antarafacial addition; the accompanying cis diastereomer resulted through the suprafacial bromine addition and rarely [4] exceeded 30% of the diastereomeric trans/cis product mixture. For the

• Hz, whereas the trans diastereomer exhibited 3J(1-H,2-H) = 1.3 Hz [6]. However, we report here on the closely related trans diastereomer of 2,3-dibromo-1,1-dimethylindane (trans-1) whose grossly deviating value of 3J(2-H,3-H) = 8.4 Hz violates the above 3JH,H rule. Results and Discussion The addition

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• functionality on the substrate in question. For example, Hayashi has shown that a rhodium/phosphoramidite catalysis is particularly effective for asymmetric [5 + 2] cycloaddition reactions (Scheme 2b). The (S,R,R)-diastereomer of the Feringa-style phosphoramidite ligand proved to be crucial to both the yield

• and enantioselectivity of this reaction, as there was a severe matched/mismatched effect observed with another diastereomer. In contrast to the ruthenium-catalyzed [5 + 2] cycloaddition of enynes, which is thought to proceed through a ruthenacyclopentene intermediate [26], it has been proposed that

• sulfinamides [48]. The application of this method to the synthesis of our chiral sulfoxide tethers is presented in Scheme 4. Tosyl protection of the primary amine of (+)-norephedrine and treatment with thionyl chloride furnishes chiral oxathiazolidine 2-oxide 7 as a single diastereomer in 87% yield over two

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

• required for manzacidin A. Possibly, the higher selectivity observed for the conversion of 29 as compared to 30 may be due to initial problems during the work-up. Finally, the addition could be effected giving the desired diastereomer 31 in high yields (72%) and the minor isomer 32 that was likewise

• obtained (24%) could be readily removed by column chromatography. The configuration of 31 was initially assigned by Mosher ester analysis of the free amine 36 (Scheme 6) and finally proven in an indirect manner by an X-ray crystallography of the minor diastereomer 32. Within the course of this study also

• acetate and finally purified by column chromatography on silica gel (120 g) with ethyl acetate/hexane 1:9 as eluent, which yielded the desired diasteromers 31 (major diastereomer) and 32 (minor diastereomer) as light yellow oils (96 %, dr = 1:3). Major diastereomer SSR (1.13 g, 3.39 mmol, 72%): Rf 0.1