Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• University, Leninskie Gory, 1, 119991, Mosсow, Russian Federation 10.3762/bjoc.16.174 Abstract A new synthetic strategy toward nonracemic phosphoryl-substituted pyrrolidines and tetrahydropyranes with three and five contiguous stereocenters is presented. Readily available β-keto phosphonates react with

• conjugated nitroolefins in the presence of a chiral Ni(II) complex to give nitro keto phosphonates with two stereocenters with excellent enantioselectivity and moderate to high diastereoselectivity. These products were used for a reductive cyclization leading to pyrrolidin-3-ylphosphonic acid and for

• to the possibility of creating enantiomerically pure compounds with several stereocenters through the directed regulation of diastereoselectivity in subsequent transformations, which can be realized as stepwise or cascade processes. Due to this reason, the Michael reaction was successfully used over

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• compounds. These compounds generally contain 9 stereocenters spread over a common (2Z,4S)-4-acetoxy-2-butenamide fragment, an (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran fragment and a terminal oxane ring joined by a dienyl chain. Due to the impressive antitumor properties of these compounds, along

• spliceostatin G (11, Scheme 25) [43]. The catalyst loading for the coupling of 130 with methyl (E)-3-iodoacrylate (20 mol %) was twice the amount used by Nicolaou (10 mol %). Conclusion As delineated above, a wide variety of synthetic strategies has been employed to either introduce the stereocenters present in

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• difficulty in generating quaternary stereocenters, the goal achieved is even more significant given the attention that the asymmetric introduction of fluorine at sp3 carbon centers has received in recent years [62][63]. A gram-scale synthesis was also successfully performed in five steps starting from the

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• temperature [32][33][34]. The anhydride was taken in slight molar excess in analogy to our previous work [21]. The reaction mixtures were heated for 6 h, until the imine 18 reacted completely. In the course of the reaction two stereocenters were formed at C-10b for 21 and C-11b for 22–24, respectively, and C

• stereochemically mobile nitrogen atom [41]. Numbers of studies suggested that the preferred conformation of benzo[a]quinolizidines depended strongly on the type of substituents, the presence of stereocenters and their configuration [36][41][42][43][44][45][46]. As for the 4-oxobenzo[a]quinolizidine derivatives, it

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• reduced gauche interactions [55]. Subsequent epoxidation at the double bond directed by the hydroxy group and using m-chloroperbenzoic acid allowed to install two additional stereocenters with complete control of the relative stereochemistry in 68% yield. Such two-step synthesis proved to proceed also in

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• . Using enantiotopically doubly 13C-2H-labeled substrates, it is possible to determine the stereochemistry of a cyclization product by locating the 2H atom and its relative position to other stereocenters [75]. In vitro terpene biosynthesis, however, might not always result in the production of the

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• towards chiral 1,4-dicarbonyls bearing tertiary and all-carbon quaternary stereocenters via oxidative cross coupling of 2-acylimidazoles 85 with silyl enol ethers 86 (Scheme 32). Chiral Rh complex 87 was exploited as a Lewis acid catalyst for the purpose of activating the substrate towards anodic

• oxidation by raising the energy of the HOMO upon enolate formation. Upon constant current electrolysis of a mixture of 85 and 86 in an undivided ElectraSyn 2.0 cell in presence of 2,6-lutidine as an external base and catalyst 87, products with tertiary carbon stereocenters as well as all-carbon quaternary

• stereocenters 88 were obtained in good yields and enatioselectivities [69]. In 2002, Dunach’s group explored an electroreductive method for the cleavage of the allyl group of β-keto ester 89 followed by the transfer of the same to the carbonyl group to afford a mixture of 91 (major), 92 and 93 (Scheme 33

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• enzymes that is widely distributed among plants, fungi and bacteria. CotB2 has evolved to convert the acyclic, achiral substrate GGDP to the 5–8–5 ring motif of cyclooctat-9-en-7-ol that contains six chiral stereocenters. Hence, CotB2 has been fine tuned to perform a highly specific regio- and

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• predominates while the imidazolidinone-catalyzed reaction is (S)-enantioselective. Nevertheless, the scope is limited to simple, achiral aldehydes. As the synthesis of more complex targets often requires functionalization of molecules with stereocenters being already installed, we wondered whether and how

Enantioselective PCCP Brønsted acid-catalyzed aza-Piancatelli rearrangement

• Gabrielle R. Hammersley,
• Meghan F. Nichol,
• Helena C. Steffens,
• Jose M. Delgado,
• Gesine K. Veits and
• Javier Read de Alaniz

Beilstein J. Org. Chem. 2019, 15, 1569–1574, doi:10.3762/bjoc.15.160

• this case with para-iodoaniline is not clear. Conclusion In summary, we have developed an efficient asymmetric aza-Piancatelli rearrangement that constructs a carbon–carbon bond plus a carbon–nitrogen bond and controls the absolute stereochemistry of the two stereocenters, through control of the

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• yersiniabactin biosynthesis (Table S2, Supporting Information File 1), which led us to infer that the absolute configuration at C-19 is S. It was hence possible to predict the configuration of all stereocenters in 1 except C-15 by bioinformatics. To conclude the stereochemical analysis, we resorted to the NOESY

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• nitroalkenes in the presence of Ni(II) complexes with various chiral vicinal diamines was studied. This reaction provides convenient access to non-racemic 4-nitro-2-sulfonylbutan-1-ones with two stereocenters with high yield and excellent enantioselectivity (up to 99%). It has been established that the

• acids are attached to 1,2-disubstituted α,β-unsaturated sulfones in the presence of the Rh/(S,S)-chiraphos catalytic system. Modern methods for the synthesis of functionalized sulfones, with stereocenters in the side chain, by Michael addition are based, mainly, on the use of vinyl sulfones as Michael

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• afford polysubstituted cyclopropanols (or cyclopropylamines) potentially bearing several diastereo- and enantiomerically enriched adjacent stereogenic centers, including quaternary carbon stereocenters, as single diastereo- and enantiomer from a simple precursor, it would certainly provide an additional

• the oxidation of the cyclopropylcopper species proceeded equally well and gave the corresponding cyclopropanols possessing two adjacent quaternary carbon stereocenters (7i–r) in good yields and excellent diastereomeric ratios. Here again, the methyl, the alkyl group from the organometallic and the

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• by many different routes, controlling the configuration of the exocyclic olefin as well as that of stereocenters on and adjacent to the three-membered ring remains a challenging task [15]. In this context, cyclopropenes can serve as useful precursors of substituted and functionalized

• to access functionalized alkylidenecyclopropanes, with creation of a new carbon–carbon bond on the three-membered ring with the control of two contiguous stereocenters. Ireland–Claisen rearrangement of cyclopropenylcarbinyl esters The Ireland–Claisen rearrangement of silyl ketene acetals generated

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• N-Boc-isatin imines 3 with silyl ketene imines 27 catalyzed using a combination of Zn(OTf)2 and chiral N,N’-dioxide ligand 28 [48]. As shown in Scheme 9, this remarkable process afforded a wide range of chiral β-amino nitriles 29 exhibiting two vicinal tetrasubstituted stereocenters as almost single

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• configuration at C4 and C5 of the target compounds 5a and 5b. After the C4-chain of tartaric acid has been extended by two carbon atoms resulting in compounds 4a and 4b, two new stereocenters have been introduced by Sharpless epoxidation [17][18]. We applied this approach for the epoxidation of 4a with L

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• stereocenters were formed giving either the syn-2 or the anti-isomers 3. In all reactions one of the diastereomers was formed in large excess. In most cases, this isomer was isolated in an almost pure form after repeated chromatography, which explains the low isolated yields. Unfortunately, all products are

• oils and could not be crystallized. Thus, in order to determine the relative stereochemistry, we analyzed the vicinal coupling constants of the protons attached to the stereocenters. In the syn-isomers 2 these protons are anti to each other, while in the anti-isomers 3 these protons are in a syn

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• bimolecular SN2 substitution would result in a complete inversion of configuration of the stereocenter and perfect enantiospecificity, while an SN1 mechanism would yield a fully racemized product. Any mixed pathway would generate products with partially racemized stereocenters. In this context, we decided to

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• significant anti-angiogenesis activity [31]. It is worth mentioning that this product has three consecutive stereocenters and different sites of variation from the original natural product. The hydride comes from the less hindered side of the ketone moiety, leading to the formation of a hydroxy group in cis

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity

• Tathagata Mukherjee,
• Soumik Biswas,
• Andreas Ehnbom,
• Subrata K. Ghosh,
• Ibrahim El-Zoghbi,
• Nattamai Bhuvanesh,
• Hassan S. Bazzi and
• John A. Gladysz

Beilstein J. Org. Chem. 2017, 13, 2486–2501, doi:10.3762/bjoc.13.246

• cases, CF2CF2OCF(CF3)CF2OCF(CF3)- segments have been found to impart higher fluorophilicites than similar perfluoroalkyl groups [42]. However, the multiple CF(CF3) stereocenters are disadvantageous, as they render such compounds mixtures of diastereomers, presenting an impediment to crystallization. In

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• . Keywords: GIAO; NMR; stereochemistry assignment; Introduction In a stereodivergent synthesis [1] often two or more new stereocenters are created with or without control of stereochemistry and it is necessary to identify the configuration of the products. Any diastereomers exhibit disparate NMR spectra

• encompass all stereomers at two selected stereocenters. Thus all possible configurations, e.g., RR, RS, SR, and SS need to be distributed to four isomeric compounds. For four different items there are overall P4 = 4! = 24 possible permutations. In other words, there are 24 ways in which configurations could

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• reduction with DIBAL-H [125]. Aldehyde (R)-17 was submitted to an asymmetric Brown crotylation reaction [126][127] to establish the C16 and C17 stereocenters. Of note, all four possible C16,C17-diastereomers of 18 were prepared (not shown) by using different combinations of (E)- or (Z)-butene and either

• moiety. The synthesis of alkyl iodide 23 departed from TBS-protected 5-hydroxypentanal 22 and proceeded via an asymmetric Brown crotylation to establish the C5 and C6 stereocenters. Intermediates 21 and 23 were combined under Smith’s modified [134] Negishi cross-coupling [124] conditions to furnish the

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• -diastereoselectivity of the CCR is well documented in the literature [33] and is, therefore, unsurprising. However, the stereocontrol achieved in this reaction over 3 stereocenters present in 10l (obtained in 81% yield as a single diastereomer) is certainly quite noteworthy and was confirmed by X-ray analysis (Figure

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• side-hydrolysis of sensitive functions, as well as epimerization of stereocenters [25]. The first condensation step leading to the thiazoline intermediate was successfully achieved, although in the presence of molecular sieves without KHCO3. The latter was then immediately dehydrated at low temperature

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

• spirocyclopentaneoxindoles. Keywords: asymmetric synthesis; four consecutive stereocenters; Michael–Henry cascade reactions; spirocyclopentaneoxindoles; thioureas; Introduction The spirocyclic oxindole core represents an important scaffold that is encountered frequently in many biologically active molecules and natural

• spirocyclopentaneoxindoles containing multiple contiguous stereocenters remains challenging [23][24][25][26]. The medicinal properties of these frameworks mean that fast enrichment of spirooxindoles bearing diverse functional groups is of considerable importance. Recently, an increasing number of asymmetric catalysis

• asymmetric catalytic synthesis of saturated spirocyclopentaneoxindoles containing four consecutive stereocenters with 3-substituted oxindoles and nitrovinylacetamide using a bifunctional thiourea catalyst in good yields (up to 95%) with excellent diastereoselectivity (up to 3:97) and enantioselectivity (up