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

• triol 16. To extend into hydrophobic chemical space around our PreQ0 analogues, we prepared two novel derivatives containing the unusual 3-arylcyclohexylamine chiral motif present in 21 and 22. Zhou et al. had reported an asymmetric synthesis leading to the cis-3-arylcyclohexanamines with reasonable

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

• sesquiterpenyl subunit in heronapyrroles A–C provoked the hypothesis that there might exist other hitherto unidentified metabolites. On biosynthetic grounds a mono-tetrahydrofuran-diol named heronapyrrole D appeared a possible candidate. We here describe a short asymmetric synthesis of heronapyrrole D, its

• produce an alternative bis-epoxy intermediate 3 that can deliver a hitherto undetected mono-tetrahydrofuran heronapyrrole (e.g., heronapyrrole D, Scheme 1). To test this hypothesis we completed an asymmetric synthesis of the putative natural product heronapyrrole D, and used this material to probe

• Streptomyces sp. (CMB-M0423) cultivations to test whether heronapyrrole D is indeed a natural product. The asymmetric synthesis of heronapyrrole D commenced with enantiomerically pure diol 8 (Scheme 2) synthesized in five steps from commercially available TIPS-protected 3-bromopyrrole 7 [3]. This reaction

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

• reduction of a prochiral ketone. The phosphoramidate (Scheme 32-iii) was the most efficient catalyst for these two reactions (ee: 95–98%, conversion 87–98%). In relation with asymmetric synthesis, the determination of the enantiomeric excess (ee) is usually achieved by different methodologies including

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• asymmetric synthesis [5][6]. Only a minor part of the chiral phosphines are chiral at the phosphorus atom (P-stereogenic) [7][8][9]. A major drawback of phosphines is their highly oxidizable nature. They are easily converted to the corresponding phosphine oxide which makes the isolation difficult. To prevent

• phosphine–borane complex 13b (Scheme 23) [165]. Chiral phosphines with a C-stereogenic center have been studied but this was the first attempt for the asymmetric synthesis of a P-stereogenic compound. After evaluating several conditions the best catalyst was (S,S)-Me-DuPhos (46). An enantioenriched

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• biological research [1][2][3][4][5][6][7][8]. In the past several years, asymmetric catalysis and auxiliary-directed asymmetric synthesis has been conducted for assembling adjacent chiral centers of boronic aicds [9][10][11][12][13], but only a few methods for generating chiral α-aminoboronic acids have been

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

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• them for the asymmetric synthesis of α-amino esters. Herein, we report for the first time the synthesis of N-phosphinyl-protected α-imino esters (Figure 1c), followed by the reduction of these α-imino esters by L-selectride, to give the corresponding α-amino esters with excellent yields (88–98%) and

• used for the asymmetric synthesis of α-amino esters through reduction. The reduction condition scan was firstly focused on the examination of reductants. A number of reductants, including Hantzsch ester, silanes, organoaluminum and boranes were tested in the system. Unfortunately, silanes failed to

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

Synthesis and stereochemical assignments of diastereomeric Ni(II) complexes of glycine Schiff base with (R)-2-(N-{2-[N-alkyl-N-(1-phenylethyl)amino]acetyl}amino)benzophenone; a case of configurationally stable stereogenic nitrogen

• Hiroki Moriwaki,
• Daniel Resch,
• Hengguang Li,
• Iwao Ojima,
• Ryosuke Takeda,
• José Luis Aceña and
• Vadim A. Soloshonok

Beilstein J. Org. Chem. 2014, 10, 442–448, doi:10.3762/bjoc.10.41

• observed depending on the substituent R introduced in the starting ligand, and stereochemical assignments were based on X-ray analysis, along with NMR studies and optical rotation measurements. Keywords: amino acids; asymmetric synthesis; Ni(II) complexes; Schiff bases; stereogenic nitrogen; Introduction

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• overcoming separation difficulties usually associated to triphenylphosphine oxide. Keywords: amino acids; asymmetric synthesis; cyclodehydration; hydroxypiperidines; natural products; one-pot; Introduction 1,2-Amino alcohols of the type A (Figure 1) represent a frequent core motif of many pharmacologically

• active natural products [1][2][3][4][5][6][7][8][9], chiral auxiliaries [10][11] and catalysts for asymmetric synthesis [12][13][14]. Especially the 2-substituted 3-hydroxypiperidine scaffold of the general structure B (as one type of an 1,2-amino alcohol) can be found in numerous natural products and

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

• -phenylmaleimide and 4-phenyltriazoline-3,5-dione. Asymmetric synthesis of a α-hydroxyalkylcyclohexane. Tandem [4 + 2]-cycloaddition/allylboration of 3-silyloxy- and 4-alkoxy-dienyl boronates. Metal-mediated cycloisomerization/Diels–Alder reaction/allylboration sequence. Cobalt-catalyzed Diels–Alder/allylboration

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• , (+)-grandiamide D, dasyclamide and gigantamide A, isolated from leaves of Aglaia gigantea, by making use of a common synthetic intermediate prepared by the Baylis–Hillman reaction. Asymmetric synthesis of the natural (+)-grandiamide D was accomplished from camphor sultam. Keywords: Baylis–Hillman reaction

• 16.6% overall yield. The spectral data obtained for synthetic compound (±)-5 matches in all respect with the data reported for the natural product [7]. Asymmetric synthesis of (+)-grandiamide D (5) In continuation, we moved on with an asymmetric approach towards the synthesis of natural product

• to get (−)-gigantamide by lipase catalyzed kinetic resolution in line with the reported method for R-jatropham [23] was not successful. Conclusion In conclusion, a facile synthesis of (±)-grandiamide D (5), dasyclamide (6) and gigantamide A (7) and asymmetric synthesis of natural (+)-grandiamide D (5

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

• deleterious epimerization of the existing stereocenter in Garner’s aldehyde. Keywords: asymmetric synthesis; Garner’s aldehyde; natural product synthesis; L-serine; Introduction “The universe is a dissymmetrical whole. I am inclined to think that life, as manifested to us, must be a function of the

• antiemetic in the 1960s. The (S)-enantiomer turned out to be teratogenic. The crucial role of chirality presents a great challenge for synthetic chemists. Asymmetric synthetic methods have emerged and after the development of ample analytical methods over the last few decades, asymmetric synthesis has seen

• formed the nucleophile reductively from pentadecyne with iBu2AlH in THF [44]. This vinylalane provided the syn-adduct 16 in modest stereoselectivity (1:2 anti/syn). For the addition reaction to be feasible for asymmetric synthesis, the configurational integrity during this step is important. Garner and

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• at C6 could not be clarified. For the epoxide moiety of curvulide A, only the relative configurations at C4 and C5 were elucidated based on H,H-coupling constants (Figure 1) [30]. So far, two syntheses of stagonolide E have been published, which both rely on asymmetric synthesis for establishing both

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

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; chiral carboxylic acids; 2-imidazolidinone; non-cross-linked polystyrene; Introduction Chiral auxiliaries have been proven as a powerful tool for the asymmetric synthesis of highly optical pure compounds used in pharmaceuticals or agrochemicals [1][2]. The recycling and reuse of expensive chiral

• for asymmetric synthesis, into the solid support [18][19]. As a part of our ongoing research, we herein report a novel NCPS-supported 2-imidazolidinone chiral auxiliary that exhibited excellent diastereocontrol. Its recycling and reuse for the synthesis of several chiral carboxylic acids are addressed

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• the total synthesis of the anticancer guaiane (−)-englerin A. A regio- and diastereoselective Co(II)-catalyzed hydration of the olefin and a transannular epoxide opening were used as the key reactions. Keywords: asymmetric synthesis; hydration; natural products; terpenes; transannular epoxide opening

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• ; Introduction The high demand of enantiopure organic compounds in the fine chemical industry gives impetus to the development of chiral technologies. Among them, the catalytic asymmetric synthesis represents the state of the art in organic chemistry [1]. Over the past four decades, the asymmetric synthesis

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• ; m.p. 55 °C; [α]D20 +260 (c 0.37, CHCl3). Other analytical data of 1 were identical to those reported by our group previously [11]. Structure of ryanodine and the Diels–Alder reactions for construction of the potential intermediates of ryanodine. Asymmetric synthesis of 7 and determination of the

• effectively promoted by TBSOTf to produce a bicyclo[3.2.2]nonene derivative bearing two quaternary carbons. Seven additional transformations from the obtained bicycle delivered the C2-symmetric bicyclo[3.3.2]decene derivative, a key intermediate in our synthetic study of ryanodine. Keywords: asymmetric

• synthesis; C2-symmetry; catalysis; Diels–Alder reaction; Lewis acid; natural product; quaternary carbon; Introduction Ryanodine (Scheme 1) [1][2][3] is a potent modulator of the intracellular calcium release channels, known as ryanodine receptors [4][5]. Its complex architecture, including eight contiguous

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• reaction of chiral imines with enolates derived from Weinreb amides [13][14]. In previous work on the asymmetric synthesis of 2,6-disubstituted piperidines by C–N bond formation, we demonstrated that intramolecular aza-Michael ”type” cyclisation [15] using a β'-carbamate-α,β-unsaturated ketone

• devised for the asymmetric synthesis of β’-amino-protected-α,β enones, a valuable intermediate for the synthesis of trans 2,6-disubstituted piperidines. The scope and limitation of the aza-Michael reaction were studied with a range of substrates. We are currently working on the application of this

• = 15.9, 4.2 Hz, 1H), 2.71 (dd, J = 15.9, 6.5 Hz, 1H), 1.19 (d, J = 6.8 Hz, 3H), 1.14 (t, J = 6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 198.8, 155.9, 143.4, 134.3, 130.6, 128.9, 128.4, 126.3, 60.6, 46.3, 44.1, 20.5, 14.6; HRMS-ESI (M + Na): calcd. for C15H19NO3Na 284.1263, found 284.1275. Asymmetric

Asymmetric Diels–Alder reaction with >C=P– functionality of the 2-phosphaindolizine-η¹-P-aluminium(O-menthoxy) dichloride complex: experimental and theoretical results

• Rajendra K. Jangid,
• Nidhi Sogani,
• Neelima Gupta,
• Raj K. Bansal,
• Moritz von Hopffgarten and
• Gernot Frenking

Beilstein J. Org. Chem. 2013, 9, 392–400, doi:10.3762/bjoc.9.40

• barrier of the Diels–Alder reaction of 7a with 1,3-butadiene, involving its attack from the Si face, is lower. It is found that in this case, the exo approach of the diene is slightly preferred over the endo approach. Keywords: aluminium(O-menthoxy) dichloride; asymmetric synthesis; >C=P– functionality

• in asymmetric synthesis, which is one of the most attractive methods from the atom-economy point of view [1] for producing single enantiomers selectively. Over the past three decades, a variety of reactions allowing the formation of C–H, C–C, C–N, C–O and other bonds enantioselectively have been

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

• the possibility of introducing further functionalization on the molecule by trapping the reactive organolithium intermediates with electrophiles. Keywords: alkenes; asymmetric synthesis; carbolithiation; carbometallation; enantioselectivity; lithium; Introduction The carbolithiation reaction has

• chiral ligands for lithium, thus opening new opportunities for their application in asymmetric synthesis. The naturally occurring alkaloid (−)-sparteine, which has been until recently inexpensive and commercially available, is the most widely used chiral ligand in enantioselective carbolithiation

Asymmetric synthesis of host-directed inhibitors of myxoviruses

• Terry W. Moore,
• Kasinath Sana,
• Dan Yan,
• Pahk Thepchatri,
• John M. Ndungu,
• Manohar T. Saindane,
• Mark A. Lockwood,
• Michael G. Natchus,
• Dennis C. Liotta,
• Richard K. Plemper,
• James P. Snyder and
• Aiming Sun

Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23

• : asymmetric synthesis; benzimidazole; host-directed; myxovirus; small molecule inhibitor; Introduction Myxoviruses are divided into two evolutionarily distinct yet related families: the orthomyxoviridae, which is composed largely of the influenza viruses, and the paramyxoviridae, which includes respiratory

• of the pure isomers for further pharmacokinetic and animal studies, we present here an asymmetric synthesis of 1 and its congeners with improved aqueous solubility and antiviral potency. Results and Discussion Design. We previously reported a series of compounds with antiviral activity against a

• )- (left, magenta) and (R)- (right, cyan) enantiomers of 1. L-Tartaric acid salt (18f-tartrate) and benzenesulfonic acid salt (18f-benzenesulfonate) of 18f. Synthesis of anilino nitrobenzene 7a. Preparation of morpholinyl-o-nitroanilines. Asymmetric synthesis of (R)- and (S)-isomers by using two different

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• of 2,2-dimethylchromene 45. Synthesis of 2,3-disubstituted chromene 47 by Stukan and co-workers. Ravichandrans synthesis of 3-substituted chromenes 52–55. Synthesis of 3-substituted chromene 58 coumarin 59 by Paye and co-workers. Govender and co-workers asymmetric synthesis of 2-phenylchromenes 62

• and 63. Asymmetric synthesis of 2-phenylchromene 62 by Li and co-workers. Acknowledgements We thank DAAD-NAPRECA for the scholarship (ZYD), the University of Botswana and the Royal Society of Chemistry for financial support.

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• amplified in recent times. In this regard, catalytic asymmetric synthesis involving the use of chiral organocatalysts has emerged as a powerful tool from the infancy to the maturity of asymmetric organocatalysis [13][14][15][16][17][18][19][20][21][22][23][24][25][26]. The use of organocatalysts for

• . Alkylation of imine Alkylation of glycine imine by using a chiral phase-transfer catalyst emerged as a very good strategy for the asymmetric synthesis of amino-acid derivatives [59][60][61]. Lamaty and co-workers prepared a series of glycine Schiff bases 22 in excellent yield (97–98%) in short reaction time