Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• therefore access to any stereoisomer at will from the same set of starting materials with full absolute and relative stereocontrol is not trivial. Previous reports show that the diastereoselection can be directed by different approaches that include the modification of reaction conditions [7][8][9], the

• involved changing the solvent to 1,2-dichloroethane [27]. As it happened in the previous case, we could observe that the reaction performed well in all cases tested and, in general, with a similar level of chemical efficiency and stereocontrol, although in comparison with the 4-catalyzed version

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• naturally occurring terpenoids is the reductive amination under Leuckart–Wallach conditions (see Scheme 2, pathway I) [39]. This method was applied to convert 2 to N-alkyl substituted menthylamines [40]. However, a significant disadvantage of this method is the lack of stereocontrol and partial inversion of

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• phosphorothioates is reason enough to investigate the synthesis of P-chiral phosphorothioates [13][14][15][16][17][18][19]. However, none of the reported methods seem to allow for routine, high-yield synthesis with high stereocontrol [20][21][22][23]. The extension to phosphorothioate RNA for applications of RNA

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

• metal-catalysed carboetherification reactions [16][17][18] and intramolecular oxycarbonylations of alkenes [19][20][21] are of particular importance. Although, many of these synthetic routes have showed their potential, there is still an area for improving the scope and stereocontrol of the new

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• employed in organic synthesis primarily as stabilized anionic nucleophiles in addition reactions to electrophilic substrates with good to excellent stereocontrol. The products obtained from these reactions were used as key building blocks in the total synthesis of a variety of structurally highly diverse

• synthetic transformations [1]. This chiral phosphonamide typically yields reaction products with excellent stereocontrol, which are easily isolated as diastereometrically pure or highly enriched compounds. Many are crystalline solids that can be purified further by recrystallization. Diazaphosphorinane 3

• high level of stereocontrol (Scheme 4) [37][38][39][40]. Thus, vicinal and quartenary carbon centers can be obtained in high diasteromeric purity by conjugate additions of allyl, crotyl, and cinnamyl-derived anions to Michael acceptors such as enones, lactones, lactams, and α,β-unsaturated esters

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• methanol. The use of 7-1 in the AT reaction in the presence of CCl4, tributylamine and aniline as a nucleophile produced 7-2 with full stereocontrol (note: due to the substitution of a hydrogen atom by an aniline moiety, the numbering used to determine the chirality at the phosphorus atom was changed

• chlorination such as the use of N-chlorosuccinimide or, as reported more recently, CuCl2 produced, in the latter case, 7-6 with full stereocontrol (Scheme 7-iii) as unambiguously determined by X-ray diffraction analysis [31]. The addition of nucleophilic species (amine, alcohol, alkyllithium, etc.) on 7-6 or

• with full stereocontrol. This result indicates that both steps (i.e., the chlorination and subsequently the substitution of the chlorine atom with the nucleophile) were stereocontrolled. The detailed mechanism of each step, which may involve penta-coordinated phosphorus intermediates [28], is not well

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• solvent [31]. The use of a stoichiometric amount of EtAlCl2 as Lewis acid catalyst allowed a lowering of the reaction temperature, a shortening of the reaction time and good stereocontrol (Scheme 2) [32]. Alternatively, the simple heating of a mixture of a 1-bora-1,3-diene, a dienophile and an aldehyde

• access to new polycyclic heterocyclic scaffolds 13 with good yields and complete stereocontrol (Scheme 11) [46]. 2-Boron-substituted 1,3-dienes In contrast to 1,3-dienes functionalized with a boron atom in position 1, only a few studies have been reported on the related dienes substituted in position 2

• finally elimination of boryl and boroxy groups. Four C–B bonds were converted into two C–C and one C=C bonds with total stereocontrol in each step (Scheme 16) [58]. 1-Boron-substituted 1,3-heterodienes 1-Oxo-4-borono-1,3-dienes In 2003, first examples of a novel diastereoselective routes to α

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

• of the seven-membered polyhydroxylated oxacycle, are for instance cycloaddition [9][10][11] or cyclodehydration of commercially available alcohols [12][13][14]. The disadvantages of these methods are the lack of selectivity as well as of stereocontrol and hence other routes are needed. One

• stereocontrol and the flexibility concerning the chain length. In 2005, Al-Harrasi synthesized the first tert-butyldimethylsilyl (TBS)-protected aminopyrans (n = 0) and aminooxepanes (n = 1) via this reaction route [23]. Several of the poly(hydroxy)aminopyrans [24] were connected to gold nanoparticles and the

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• (−)-quinic acid (16) according to the route reported by Arthurs et al. [40] with minor modifications. After Baylis–Hillman reaction and subsequent silylation of the resulting free primary hydroxy group, substrate-controlled α-methylation of the lithium enolate proceeded with full stereocontrol [41][42

• control [58]. The configuration was determined by the high coupling constant (JH4/H5 = 12.6 Hz) indicating the trans-diaxial orientation of H4 and H5. Silylation of the primary hydroxy group afforded compound 84 that was converted into the epoxide with complete stereocontrol [59]. The epoxide underwent

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

• steps proceeded in good to very good overall yield and stereocontrol. The developed synthesis may therefore be a complement to the existing literature. An attempted synthesis of an azepane ring-modified balanol derivative from a common precursor unfortunately was unsuccessful due to difficulty in

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• and affecting the selectivity with opposite stereocontrol [58]. In 1988, in pioneering work independently done by Herold [59] and Garner [44] investigated the use of chiral aminoaldehydes as intermediates for the synthesis of nitrogen containing natural products. Both groups realized that the

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• -benzyloxycarbonyl group imposed A1,3-strain on piperidine derivatives founded the basis for the observed stereocontrol. Thus, we chose keto-lactam 10 as our substrate. Although compound 10 is not a urethane, and a A1,3-strain not longer exists, a simple chair conformational-controlled preferential equatorial attack

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• , cycloadditions are atom economical, and usually take place with high levels of regio- and stereocontrol. Especially relevant in terms of synthetic practicality are cycloadditions which are catalyzed by transition metal complexes [19][20][21][22][23]. In particular, gold(I) complexes, owing to their high

Non-cross-linked polystyrene-supported 2-imidazolidinone chiral auxiliary: synthesis and application in asymmetric alkylation reactions

• Quynh Pham Bao Nguyen and
• Taek Hyeon Kim

Beilstein J. Org. Chem. 2013, 9, 2113–2119, doi:10.3762/bjoc.9.248

• auxiliaries have not been widely investigated yet [13][14][15][16][17][18][19][20][21][22][23][24][25][26]. In this field, solid supported chiral auxiliaries such as Evans' 2-oxazolidinones [13][14][15][17] and pseudoephedrines [16][22] have been mainly explored, however, a high stereocontrol has still not

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• stereocontrol for these apparent anomalies. In particular, we wanted to better understand if the imine carbonyl substituents of cis-imines, from imines with a mediocre cis/trans ratio, were reducing the facial selectivity (because of conformational effects) of these N-chiral imines, while the corresponding

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• groups using Ac2O and pyridine afforded the separation of the components and disaccharide 20b was then isolated with complete stereocontrol in 41% yield after the 3 steps. Adamantanyl thiosialosides have been shown to have high reactivity under NIS/TfOH promotion conditions in nitrile solvents at −35 °C

Development of an additive-controlled, SmI₂-mediated stereoselective sequence: Telescoped spirocyclisation, lactone reduction and Peterson elimination

• Brice Sautier,
• Karl D. Collins and
• David J. Procter

Beilstein J. Org. Chem. 2013, 9, 1443–1447, doi:10.3762/bjoc.9.163

• to “switch on” individual steps mediated by the electron transfer reagent. The sequence involves the use of two activated SmI2 reagent systems and a silicon stereocontrol element that exerts complete diastereocontrol over the cyclisation and is removed during the final stage of the sequence by

• ” individual steps: spirocyclisation, lactone reduction and Peterson elimination allow rapid access to functionalised cyclopentanols, containing two vicinal quaternary stereocentres, from simple starting materials. The sequence involves the use of two activated SmI2 reagent systems, and a silicon stereocontrol

• elimination of triols 3 would result in removal of the silicon stereocontrol element used to control the stereochemical course of C–C bond formation. In early studies, treatment of triol 3b with t-BuOK gave vinyl cyclopentanol 5b in moderate yield [45], but the reaction suffered from poor reproducibility

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

• Hideto Miyabe,
• Ryuta Asada and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2013, 9, 1148–1155, doi:10.3762/bjoc.9.128

• (Figure 1) [37][38][39][40][41][42][43]. Enantioselective radical reactions have been intensively studied over the past fifteen years. Compared with stereocontrol studies on intermolecular radical reactions, the enantioselective stereocontrol in radical cyclizations still remains a major challenge [44][45

• a carbon–carbon double bond, e.g., a methacryloyl group, of the electron-deficient acceptor is essential for the successful cascade transformation. To gain further insight into the stereocontrol in the cyclization step, we next studied the opposite regiochemical cyclization by using the substrate 12

Enantioselective reduction of ketoimines promoted by easily available (S)-proline derivatives

• Martina Bonsignore,
• Maurizio Benaglia,
• Laura Raimondi,
• Manuel Orlandi and
• Giuseppe Celentano

Beilstein J. Org. Chem. 2013, 9, 633–640, doi:10.3762/bjoc.9.71

• involves the formation of a hydrogen-bond between the amide group of the catalyst and the substrate as a necessary element for stereocontrol (for another example of relevant N-formyl proline derivative see [12]). Also in Sun catalysts F [13][14] and sulfinamide G [15] as well as in chiral picolinamides H

• ., 59% and 62% ee, respectively. Increasing the steric hindrance on the aromatic ring did not improve the enantioselectivity and it generally lowered the chemical activity. A pyridine ring had no positive effect on the process in terms of stereocontrol (Table 2, entry 7), probably due to its

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• exceedingly potent Claisen rearrangement [37], with the attending advantages of stereocontrol and chirality transfer. Another powerful approach to polycyclic structures is through association with Robinson-type annelations [38]. The synthesis of the precursors also exploits the Claisen rearrangement, as shown

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• transition state in which the lithium atom is coordinated to the remote π-bond [30][31][32]. This high stereocontrol has allowed the synthesis of enantiomerically pure carbocycles and heterocycles through diastereoselective cyclization of chiral nonracemic substrates [33][34][35][36][37][38]. Additionally

Alternaric acid: formal synthesis and related studies

• Michael C. Slade and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19

• insufficient for adequate stereocontrol in the three-component coupling reaction [34]. An additional branch point in the carbon backbone, such as in 16b, was deemed necessary. The 1,3-dithiane group in aldehyde 16ba was conceived as a promising candidate for a stereocontrolling element due to its large size

Alkenes from β-lithiooxyphosphonium ylides generated by trapping α-lithiated terminal epoxides with triphenylphosphine

• David. M. Hodgson and
• Rosanne S. D. Persaud

Beilstein J. Org. Chem. 2012, 8, 1896–1900, doi:10.3762/bjoc.8.219

• with high regio- and stereocontrol (Scheme 1) [1][2][3][4][5][6][7][8][9]. These ylide intermediates can be generated by initiating a Wittig reaction between an aldehyde 1 and a phosphorane 2 at low temperature in the presence of lithium salts, which promote ring opening of the initially formed

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• strategy for ensuring effective stereocontrol to achieve completion of the target-directed synthesis. The overall yield in 22 steps from 2,3,5-tri-O-benzyl-L-arabinose (3) was 3.9%. Although 1b and its related analogues are now accessible through the pathway established above, pursuing a new synthetic