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

• characteristic (Z,Z,E)-triene, a thiazole side chain and a characteristic sequence of eight methyl and hydroxy-bearing stereocenters. Synthetic chemistry is of key importance to enhance the supply of these scarce polyketides to fully evaluate the biological potential and develop them as potential drug candidates

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• functionality in a defined way in three dimensions, allowing them to bind their biological targets with useful affinity (10−7 to 10−9 M [4]). Erythromycin A (1, Figure 1) is the prototypical polyketide, as its biosynthesis has been studied most heavily to date. The structure incorporates 10 stereocenters, and

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• ) were obtained for a series of spirocyclic 1,4-sulfur-bridged piperidinone-based succinimides. Keywords: [4 + 2] annulation; asymmetric organocatalysis; dipeptide-based Brønsted bases; 5H-thiazol-4-ones; N-itaconimides; Introduction Sulfur-containing tetrasubstituted carbon stereocenters are widely

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

• of the stereocenters of compounds 4 are 2’R*, 3aS*, 3’R*, 4’R*, 9aR*. The homogeneity of compounds 4b–d,f–i,l–n was additionally confirmed by powder X-ray diffraction. The analysis of the experimental powder diffraction patterns of compounds 4b–d,f–i,l–n show that the investigated samples were single

• 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

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• efficient construction of vicinal quaternary and tertiary stereocenters [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. In particular, the application of 3-aryl substituted oxindoles seems problematic; hence, the full potential of this useful carbon–carbon bond formation is yet to be realized [12

• -butylphenyl group, delivered a critical improvement in diastereoselectivity, affording 4aa quantitatively and establishing consecutive quaternary and tertiary stereocenters with almost complete fidelity (Table 1, entry 3). Further examination of the reactions under the influence of 1d, having 3,5-bis

• the scope of this mode of stereoselective Mannich-type reaction, which involve the generation of vicinal quaternary and tertiary stereocenters. Further investigations into the potential utility of ammonium betaine catalysis are underway in our laboratory. Chiral ammonium betaines. ORTEP diagram of 4ca

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

• . Deuterium labeling experiments have shown that the hydrogenation reaction occurs only on the chiral keto tautomer, and therefore the catalyst selects one enantiomer of the substrate when the reduction takes place. Enantioconvergent methods are not limited to carbon stereocenters. An exceptional example of

• reaction was reported by Stoltz for the generation of enantioenriched all-carbon quaternary stereocenters from racemic allyl β-ketoesters (e.g., (±)-20 → (+)-23, Scheme 5) [29]. This particular reaction is especially unusual since the stereoablative step requires scission of a C–C bond at a quaternary

Application of heterocyclic aldehydes as components in Ugi–Smiles couplings

• Katelynn M. Mason,
• Michael S. Meyers,
• Abbie M. Fox and
• Sarah B. Luesse

Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191

• Diels–Alder (US-IMDA) reaction with substituted 2-furaldehyde and allylamine (Scheme 1), which provides direct access to N-arylepoxyisoindolines 1 through a simple, one-pot reaction [23]. Through this stereoselective tandem process, six new bonds and four stereocenters are generated in one synthetic

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• compound 2a was formed from the corresponding O-allyl compound via CR. Based on the X-ray structure of 1a and the above observations, it is clear that the allyl groups in 2a are in endo configuration which can be explained as follows. Since the stereocenters are unaffected during the RCM sequence it is

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

• attack of the secondary hydroxy group to the oxocarbenium ion Y led to a stable six-membered pyranose ring compound thus shifting the equilibrium in favour of bridged bicyclic system 12/13. In order to validate the configurational assignments at the newly generated stereocenters, the coupling constants

• configuration at the newly generated stereocenters at C5’ and C6’ (corresponding to the C7 and C8 of epoxide 8) [20]. In the 1H NMR of 14, appearance of a triplet at δ 2.30 (J = 12.7 Hz) and a doublet of doublet at δ 2.09 (J = 12.7 and 4.7 Hz), integrating for one proton each, were assigned to the methylene

• orientation indicating 5’S absolute configuration as anticipated from the SAE mnemonic in compound 8. As the C5’ and C6’ stereocenters in 14 are derived from the regioselective SN2 opening of epoxide 8 by NaN3, the configuration at the C6’ (carrying azido group) was therefore assigned as 6’R. In the 1H NMR

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

• researchers have developed methods for the stereoselective synthesis of tertiary carbon stereocenters. One aesthetically pleasing approach is the enantioselective protonation of prochiral enolates and enolate equivalents [1][2][3][4][5][6][7][8][9][10]. While an attractive strategy, the enantioselective

• additions to other classes of Michael acceptors only being reported more recently. While many examples using sulfur and carbon nucleophiles have been reported, the addition of other heteroatom nucleophiles remains relatively unexplored. This approach for the synthesis of tertiary carbon stereocenters

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

• asymmetric ruthenium-catalyzed cycloisomerization reactions in the literature. In 2011, our research group disclosed the ruthenium-catalyzed redox bicycloisomerization of 1,6- and 1,7-enynes to construct structurally complex [3.1.0] and [4.1.0] bicycles containing vicinal, quaternary all-carbon stereocenters

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

• devoted to the development of new efficient chiral catalysts, both metal catalysts and organocatalysts, together with the search for appropriate (pro)nucleophiles and/or electrophiles. In this context, the enantioselective construction of tetrasubstituted stereocenters is another challenge [5][6][7][8][9

Indenopyrans – synthesis and photoluminescence properties

• Andreea Petronela Diac,
• Ana-Maria Ţepeş,
• Albert Soran,
• Ion Grosu,
• Anamaria Terec,
• Jean Roncali and
• Elena Bogdan

Beilstein J. Org. Chem. 2016, 12, 825–834, doi:10.3762/bjoc.12.81

• ] may lead to two possible regioisomers: isomer 2 with the benzene ring fused at C5a–C9a and its regioisomer 3 with the benzene ring fused at C4b–C8a (Figure 1). Additionally, due to the new stereocenters created at positions 4 and 4a, each regioisomer could be expressed as a set of diastereoisomers

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

• giving four diastereoisomers instead [21]. Finally, the sulfa-Michael/nitroaldol cascade reaction was applied to other trans-β-methyl-β-nitrostyrenes under the optimized conditions (Table 3). Tetrahydrothiophenes, bearing three contiguous stereocenters, were isolated in good to high yield, moderate

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• first tested in the reaction of trans-nitrostyrene (1a) with diethyl malonate (2a), leading to the enantioenriched addition product 4aa with a single stereocenter. In order to the creation of two tertiary-quaternary contiguous stereocenters (5aa) we also used ethyl 2-oxocyclopentanecarboxylate (3a) as

• higher than 90:10, although the stereoselectivity for the reaction leading to 4ag, with two contiguous tertiary–quaternary stereocenters was only moderate (dr 75:25, entry 8 in Table 2). The main difference in those additions was related with the reaction time, because the less reactive malonates (2b and

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• 39 reacted to give the quaternary stereocenters-containing products 42 with high diastereoselectivity (up to > 99:1 dr) and enantioselectivity (up to 90% ee). A bifunctional role played by the catalyst was again envisioned by the authors. In the transition state TS13 the tertiary amine group of the

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• diastereoselectivity >99:1. Tertiary amine-(thio)ureas as organocatalysts promoting asymmetric transformations that lead to a six-membered ring One-step reactions producing six-membered rings In 2008, the first example of a single reaction producing a six-membered ring with multiple stereocenters catalyzed by a

• 64 in good yield. The substrate scope of this reaction was thoroughly studied and the products of the transformation were exploited to generate a variety of γ-amino acids, including examples containing three contiguous stereocenters. In 2010, Yan and co-workers described the Michael addition of

• multiple contiguous stereocenters, including one quaternary center [35]. The reaction proceeded smoothly and a wide range of products 75 were obtained in good yields and moderate to excellent stereoselectivity (Scheme 26). The authors proposed that the organocatalyst deprotonates substrate 73 to produce a

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• -pyrrol-2(3H)-ones bearing quaternary stereocenters were obtained in acceptable yield (up to 75%) and enantioselectivity (up to 73% ee). Keywords: asymmetric catalysis; bifunctional catalysts; Henry reaction; organocatalysis; 1H-pyrrole-2,3-diones; Introduction Asymmetric organocatalysis has been

• quaternary stereocenters [35][36][37], we envisioned that the Henry reaction of nitroalkanes with 1H-pyrrole-2,3-diones should take place with a chiral bifunctional amine-thiourea catalyst, leading to 3-hydroxy-3-nitromethyl-1H-pyrrol-2(3H)-ones bearing quaternary stereocenters (Scheme 1) [14]. Notably, this

• -pyrrole-2,3-diones with a chiral bifunctional amine-thiourea possessing multiple hydrogen-bond donors as the catalyst. With the developed protocol, a range of 3-hydroxy-3-nitromethyl-1H-pyrrol-2(3H)-ones bearing quaternary stereocenters were obtained in good yield (up to 75%) and with moderate to good

Asymmetric α-amination of β-keto esters using a guanidine–bisurea bifunctional organocatalyst

• Minami Odagi,
• Yoshiharu Yamamoto and
• Kazuo Nagasawa

Beilstein J. Org. Chem. 2016, 12, 198–203, doi:10.3762/bjoc.12.22

• important synthetic route to optically active α-amino acid derivatives with chiral quaternary stereocenters [1][2]. Since an α-amino acid moiety is frequently found in biologically active compounds, considerable efforts have been made to achieve a stereoselective synthesis of this structure [3][4]. In

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• of tertiary carbon stereocenters, remains an ongoing challenge. Over the last decades though, transition metal-catalyzed reactions like the asymmetric allylic alkylation (Tsuji–Trost reaction) have evolved into one of the more powerful tools for synthesizing such tertiary stereocenters [7][8]. As a

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• with pyridines. In 2011, Maruoka and co-workers investigated the use of isoquinolinium ions protected as azomethine imines [30]. The use of a CuOAc/Ph-Pybox catalyst enables the addition of a wide variety of alkynes to form isoquinolines with tertiary stereocenters in high yields and ee’s (Scheme 8A

• ). Although lower ee’s were observed with o-tolylacetylene (43% ee) and 1-heptyne (75% ee), all other alkynes resulted in ≥85% ee. Even more impressive, the authors discovered conditions for a highly enantioselective alkynylation to form tetrasubstituted stereocenters. With 1-alkylisoquinolinium ions, high

• substrates, suggesting that more stable oxocarbenium ions result in more selective reactions, potentially because they lead to later enantiodetermining transition states. We have also discovered a CuSPh/Ph-Pybox catalyst that enables the formation of diaryl, tetrasubstituted stereocenters via an

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

• enantioselective intramolecular oxa-Michael reaction of an α,β-unsaturated amide mediated by a newly developed benzothiadiazine catalyst. The Weinreb amide moiety and bromo substituent of the Michael adduct were utilized for the C–C bond formations to construct the scaffold. All four contiguous stereocenters of

• clinical application of 1, as well as the development of more active derivatives. Due to the unique tricyclic core of 1, which bears four contiguous stereocenters, various approaches for the synthesis of key intermediate 2 (Scheme 1) have been reported [14][15][16][17][18][19][20][21][22][23], including a

• , the proposed strategy offers an efficient construction of all stereocenters of tricyclic core 2, based on the initially established chiral stereocenter, as the configuration at the C1 and C2 positions of 2 would presumably be controlled by face-selective reduction of ketone 3. The Michael precursor 7

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

• (Scheme 16). In 2014, Cai et al. [46] applied the desymmetrization strategy to construct chiral cyano-bearing all-carbon quaternary stereocenters, affording 1,2,3,4-tetrahydroquinoline analogues in good yields and excellent enantioselectivities (Scheme 17). The same group also observed that achiral

• -substituted quaternary stereocenters (Scheme 22). Asymmetric C–O coupling Numerous methods have been developed during the last two decades for the formation of aryl C–O bonds but asymmetric aryl C–O coupling is still a challenge [6][7][8][9][10]. In 2013, Beaudry and Quamar Salih reported the first copper

• -halophenoxyl)-1,3-diols by the same group [54]. However, the palladium catalytic systems suffered from limited substrate scope and poor efficiency and enantioselectivity for the formation of quaternary stereocenters. Recently, Cai et al. carried out such couplings using a CuI/cyclized diamine catalytic system

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

• blumiolide C was accomplished in an overall yield of 0.63%. In 2005, Hiersemann and co-workers reported an approach towards the synthesis of xeniolide F [13] employing a catalytic asymmetric Claisen rearrangement to set the crucial stereocenters at the C2 and C3 positions (Scheme 10) [54]. The synthesis

• butenolide 140 from (R)-citronellol (139) in an 11-step sequence. Next, the two stereocenters at C2 and C3 position were installed by stereoselective conjugate addition of enantiopure α-allylphosphonamide 141 to butenolide 140. After cleavage of the chiral auxiliary by ozonolysis, aldehyde 142 was protected

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• rearrangements and cyclizations experimentally. The structure elucidation of terpenoids can be challenging because of the multicyclic carbon skeletons with several contiguous stereocenters. The assistance of 13C labels can in such cases be especially helpful, and if completely 13C-labeled carbon backbones can be

• stereocenters deduced from labeling experiments. Structure of thiomarinol A (27). Bold bonds indicate carbon atoms derived from 4-hydroxybutyrate. Structures of artemisinin (28), ingenol (29) and paclitaxel (30). The revised (31) and the previously suggested (32) structure of hypodoratoxide and the structure of