Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• The discovery of new chiral ligands and auxiliaries continues to expand the frontiers of catalytic asymmetric synthesis. In particular, C2-symmetric diols, such as (S)-BINOL (1) [1] and (−)-TADDOL (2) [2] (Figure 1), have garnered considerable attention owing to the wide variety of asymmetric

• with the reported synthesis and should be effective for the rapid production of new ligands for asymmetric synthesis. Conclusion In conclusion, an efficient and economical process was developed for the direct functionalization of hydrobenzoin that relies on a directed ortho,ortho'-dimetalation strategy

• asymmetric synthesis and the tetralithio intermediate 8. Percentage of (R,R)-hydrobenzoin (3) (○), monodeuterohydrobenzoin (13) (■), and dideuterohydrobenzoin (9) (Δ) as determined by mass spectrometry (ESI) [23]. Percentage of methylhydrobenzoin (14) (■), and dimethylhydrobenzoin (15) (Δ) as determined by

Synthesis of enantiomerically enriched (R)-¹³C-labelled 2-aminoisobutyric acid (Aib) by conformational memory in the alkylation of a derivative of L-alanine

• Stephen P. Fletcher,
• Jordi Solà,
• Dean Holt,
• Robert A. Brown and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1304–1309, doi:10.3762/bjoc.7.152

• product was established. Keywords: amino acid; asymmetric synthesis; conformational memory; isotopic label; isotopomer; quaternary stereogenic centre; Introduction In connection with our work on the control of conformation in helical foldamers [1][2][3] built from quaternary α-amino acids [4][5], we

• common component of several fungal and bacterial antibiotic metabolites [14], and the helix-forming properties of these metabolites, which encourage them to embed themselves into cell membranes, are at the origin of their biological activity. The methods available for the asymmetric synthesis of

Directed aromatic functionalization

• Victor Snieckus

Beilstein J. Org. Chem. 2011, 7, 1215–1218, doi:10.3762/bjoc.7.141

• , representative of the subject areas described above, demonstrates the current activity in aromatic chemistry. For example, the DoM reaction as applied to the construction of molecules of value for asymmetric synthesis is nicely presented by Rob Britton; lithiation chemistry in service of heterocyclic synthesis

Asymmetric Au-catalyzed cycloisomerization of 1,6-enynes: An entry to bicyclo[4.1.0]heptene

• Alexandre Pradal,
• Chung-Meng Chao,
• Patrick Y. Toullec and
• Véronique Michelet

Beilstein J. Org. Chem. 2011, 7, 1021–1029, doi:10.3762/bjoc.7.116

• evaluated: The corresponding bicyclic adducts 4e and 4f were isolated in modest to good yield and 95% ee. Considering the observed highly stereoselective reactions of oxygen-tethered 1,6-enynes, we decided to study the challenging asymmetric synthesis of pentasubstituted cyclopropyl derivatives [67][68][69

• (99.9:0.1), flow rate 0.5 mL/min, λ = 215 nm): retention times 11.8 and 12.6 min, ee 73%; [α]D23 +11.7 (c 1, CHCl3). First reports on the racemic and asymmetric synthesis of bicyclo[4.1.0]heptenes. Synthesis of oxygen-tethered 1,6-enynes. Nitrogen-tethered 1,6-enynes. Synthesis of pentasubstituted

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

Alkene selenenylation: A comprehensive analysis of relative reactivities, stereochemistry and asymmetric induction, and their comparisons with sulfenylation

• Vadim A. Soloshonok and
• Donna J. Nelson

Beilstein J. Org. Chem. 2011, 7, 744–758, doi:10.3762/bjoc.7.85

• selenenylation; asymmetric synthesis; calculations; electronic effects; regioselectivity; relative reactivities; steric effects; Introduction Electrophilic addition to alkenes is one of the most fundamental, generalized, and versatile methods for selective functionalization of hydrocarbons [1]. Despite recent

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• /hydroboration/oxidation, which gave the best results when the Hoveyda–Grubbs catalyst 6 was used in the RCM (Scheme 15). Interestingly, in this case the asymmetric synthesis of the protected RCM precursor 78 started from a non-chiral source, the alcohol 75, and proceeded with complete stereocontrol over the 11

• promoted by the 1st-generation Grubbs catalyst 2 is starring again in the divergent, flexible methodology disclosed by Singh and Han [69] for the asymmetric synthesis of several deoxyiminocyclitols (1-deoxymannonojirimycin (63), 1-deoxyaltronojirimycin (65), 1-deoxygulonojirimycin (91), 1

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• medicinal chemistry, surprisingly few effective methods are suitable for the asymmetric synthesis of tertiary thiols. This review details the most practical of the methods available. Keywords: asymmetric synthesis; organolithium; sulfur; substitution; thiol; Introduction Organosulfur compounds play key

• , sulfimines and sulfilimines [9]. Chiral sulfoxides and sulfonium ylids have themselves been extensively used as tools for asymmetric synthesis [3]. With regard to chiral sulfur(II) compounds – namely thiols and thioethers (sulfides) with chirality at carbon – methods available for their asymmetric

• preparation are abundant, and usually rely on stereospecific substitution reactions [9]. These reactions are well suited to the construction of secondary thiol derivatives. By contrast, few methods are suitable for the asymmetric preparation of simple tertiary thiols 1. While the asymmetric synthesis of

Synthesis of 5-(2-methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene as 2,2'-disubstituted 1,1'-binaphthyls via benzannulated enyne–allenes

• Yu-Hsuan Wang,
• Joshua F. Bailey,
• Jeffrey L. Petersen and
• Kung K. Wang

Beilstein J. Org. Chem. 2011, 7, 496–502, doi:10.3762/bjoc.7.58

• '-diol (BINOL) and BINOL derivatives as reagents in asymmetric synthesis has stimulated the development of new synthetic methods for 2,2'-disubstituted 1,1'-binaphthyls [8][9][10][11][12][13][14][15][16]. However, the great majority of the reported methods involved coupling of two properly substituted 1

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

Application of the diastereoselective photodeconjugation of α,β-unsaturated esters to the synthesis of gymnastatin H

• Ludovic Raffier and
• Olivier Piva

Beilstein J. Org. Chem. 2011, 7, 151–155, doi:10.3762/bjoc.7.21

• Ludovic Raffier Olivier Piva Université Lyon 1, UMR 5246 CNRS, Institut de Chimie et de Biochimie Moléculaire et Supramoléculaire, 69622 Villeurbanne, France 10.3762/bjoc.7.21 Abstract The asymmetric synthesis of gymnastatin H has been achieved by using the photoisomerisation of a conjugated

• application to the asymmetric synthesis of different natural products including (R)-lavandulol (8), (R)-arundic acid (9) and 2-fluoroacids or lactones [7][8][9] (Figure 1). Filamentous fungi are the source of a wide range of secondary metabolites which possess very promising biological activities. Among them

Light-induced olefin metathesis

• Yuval Vidavsky and
• N. Gabriel Lemcoff

Beilstein J. Org. Chem. 2010, 6, 1106–1119, doi:10.3762/bjoc.6.127

• ], ultimately led to the 2005 Nobel Prize award to Yves Chauvin, Richard Schrock and Robert Grubbs [21] for the development of this reaction. Since, olefin metathesis has seen much progress, such as the use of new ligands for aqueous applications [22][23][24][25][26], asymmetric synthesis [27][28][29][30] and

Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

• Michael North and
• Marta Omedes-Pujol

Beilstein J. Org. Chem. 2010, 6, 1043–1055, doi:10.3762/bjoc.6.119

• Michael North Marta Omedes-Pujol School of Chemistry and University Research Centre in Catalysis and Intensified Processing, Bedson Building, University of Newcastle, Newcastle upon Tyne, UK, NE1 7RU 10.3762/bjoc.6.119 Abstract Propylene carbonate can be used as a green solvent for the asymmetric

• synthesis of cyanohydrin trimethylsilyl ethers from aldehydes and trimethylsilyl cyanide catalysed by VO(salen)NCS, though reactions are slower in this solvent than the corresponding reactions carried out in dichloromethane. A mechanistic study has been undertaken, comparing the catalytic activity of VO

α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

• David. M. Hodgson and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2010, 6, 978–983, doi:10.3762/bjoc.6.110

• ]-anionic phosphonyl group migration under experimentally straightforward conditions, to provide a stereocontrolled access to synthetically valuable trans-α,β-aziridinylphosphonates. The utility of this chemistry has been demonstrated in the asymmetric synthesis of a β-aminophosphonate. Keywords: amino

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• this field is in constant development. Keywords: asymmetric synthesis; electrophilic; fluorine; reagent; trifluoromethylation; Review The chemistry of fluoro-organic compounds is one of the areas of the life sciences that have developed most rapidly over the last 50 years, despite the fact that

Bis(oxazolines) based on glycopyranosides – steric, configurational and conformational influences on stereoselectivity

• Tobias Minuth and
• Mike M. K. Boysen

Beilstein J. Org. Chem. 2010, 6, No. 23, doi:10.3762/bjoc.6.23

• revealed strong steric and configurational effects of position 3 on asymmetric induction, further dramatic effects of the pyranose conformation were also observed. Keywords: asymmetric synthesis; carbohydrates; copper; cyclopropanation; ligand design; Introduction The design and optimisation of chiral

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.0^2,6]decane skeleton

• Matthias Breuning,
• Tobias Häuser,
• Christian Mehler,
• Christian Däschlein,
• Carsten Strohmann,
• Andreas Oechsner and
• Holger Braunschweig

Beilstein J. Org. Chem. 2009, 5, No. 81, doi:10.3762/bjoc.5.81

• of 11 delivered the exo-configured alcohol rac-12, which was oxidized with PCC furnishing rac-9 in 79% yield. The asymmetric synthesis of the ketone 9 was realized by enantioselective hydration of the meso-alkene 11 using Hayashi’s method (Scheme 2) [25][26][27][28][29][30]: Hydrosilylation with

Continuous flow enantioselective arylation of aldehydes with ArZnEt using triarylboroxins as the ultimate source of aryl groups

• Julien Rolland,
• Xacobe C. Cambeiro,
• Carles Rodríguez-Escrich and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2009, 5, No. 56, doi:10.3762/bjoc.5.56

• : asymmetric synthesis; continuous flow; diarylmethanols; solid-supported catalyst; triarylboroxins; Introduction Diarylmethanols constitute the basic scaffold in several important drugs such as antihistamines and muscle relaxants (R)-neobenodine, (R)-orphenadrine or (S)-carbinoxamine (Figure 1) [1]. Despite

• the apparent simplicity of the structures, their asymmetric synthesis is not trivial. For instance, access to these structures through enantioselective reduction of the corresponding ketones can become troublesome when both aryl groups are similar in their electronic and steric properties [2][3][4

Iridium-catalyzed asymmetric ring-opening reactions of oxabicyclic alkenes with secondary amine nucleophiles

• Dingqiao Yang,
• Ping Hu,
• Yuhua Long,
• Yujuan Wu,
• Heping Zeng,
• Hui Wang and
• Xiongjun Zuo

Beilstein J. Org. Chem. 2009, 5, No. 53, doi:10.3762/bjoc.5.53

• the desired products in moderate to good yields with good enantioselectivities. The iridium-catalyzed ARO reactions described in this article featured lower cost compared with rhodium-catalyzed ARO reactions, which provided potential applications in asymmetric synthesis of chiral building blocks. The

2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β²-amino acids

• Markus Nahrwold,
• Arvydas Stončius,
• Anna Penner,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43

• serve as universal precursors for the asymmetric synthesis of functionalised β2-amino acids containing acid-labile protected side chains. Diastereoselective alkylation of the tetrahydropyrimidinone is followed by a chemoselective two step degradation of the heterocycle to release the free β2-amino acid

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• coupling Recently the Michael group proposed a formal enantioselective asymmetric synthesis of an aziridinomitosene also based on an intramolecular Heck coupling [150]. They succeeded in incorporating all the reactive functionalities, namely the quinone, the carbamate and the aziridine and thus bypassed

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• Xiao Yin Mak Paola Laurino Peter H. Seeberger Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Research Campus Golm, D-14424 Potsdam, Germany 10.3762/bjoc.5.19 Abstract An overview of asymmetric synthesis in continuous flow and microreactors is presented in

• transformed directly into enantioenriched products using only minute amounts of a renewable chiral component [9]. The potential applications of continuous flow technology as a valuable tool for asymmetric synthesis has been demonstrated in terms of fast optimization studies, improved control of reaction

• of asymmetric synthesis using solid-supported catalysts is the development of an immobilization strategy that maintains both good stereoselectivity and catalyst activity. Selectivities obtained using homogeneous catalysts that work well in solution phase can often be significantly reduced when

Enantiospecific synthesis of [2.2]paracyclophane- 4-thiol and derivatives

• Gareth J. Rowlands and
• Richard J. Seacome

Beilstein J. Org. Chem. 2009, 5, No. 9, doi:10.3762/bjoc.5.9

• has the potential to produce a wide-range of thiol derivatives and this has permitted the first synthesis of a planar chiral benzothiazole, [2.2](4,7)benzo[d]thiazoloparacyclophane. The use of these thiols in asymmetric synthesis is currently being investigated and will be reported in due course

Asymmetric synthesis of biaryl atropisomers by dynamic resolution on condensation of biaryl aldehydes with (−)-ephedrine or a proline- derived diamine

• Ann Bracegirdle,
• Jonathan Clayden and
• Lai Wah Lai

Beilstein J. Org. Chem. 2008, 4, No. 47, doi:10.3762/bjoc.4.47

Radical cascades using enantioenriched 7-azabenzonorbornenes and their applications in synthesis

• David M. Hodgson and
• Leonard H. Winning

Beilstein J. Org. Chem. 2008, 4, No. 38, doi:10.3762/bjoc.4.38

• -azabenzonorbornadienes. Oxidation (using RuO4) and Birch reduction of the 2-aza-5,6-benzonorbornenes provide access to substituted pyrrolidines and tetrahydroindenes, respectively. Keywords: asymmetric synthesis; deoxygenation; radicals; rearrangements; tandem reactions; Introduction Carbon-centred radicals have been