Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• chemoselective) reactions have been reported [1][2][3]. However, one drawback of this approach is the requirement of the removal of the metal impurity from the products. An organocatalytic approach is attractive in this sense as it is metal-free, cost-effective, and favoured by the pharmaceutical industry for

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• 21. After chemoselective, acid-catalyzed deprotection, the liberated amines were coupled with the Boc-protected cysteine tert-butyl disulfide 22. The obtained amide 23 was treated with TFA for Boc removal and coupled with the geminal diphosphonate foot 7. Deprotection of both hydrazides and

Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters

• Gehad Zeyat and
• Karola Rück-Braun

Beilstein J. Org. Chem. 2012, 8, 890–896, doi:10.3762/bjoc.8.101

• chemoselective bimolecular thioester exchange prior to the S- to N-acyl transfer through a five-membered transition state for Cys-peptide 3, a six-membered transition state for 4,5,6-trimethoxy-2-mercaptobenzyl auxiliary peptide 5, and a sterically more demanding five-membered transition state for racemic Nα-2

Formation of carbohydrate-functionalised polystyrene and glass slides and their analysis by MALDI-TOF MS

• Martin J. Weissenborn,
• Johannes W. Wehner,
• Christopher J. Gray,
• Robert Šardzík,
• Claire E. Eyers,
• Thisbe K. Lindhorst and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 753–762, doi:10.3762/bjoc.8.86

• generally compatible with other platforms in our laboratories, such as through the formation of SAMs on gold [18] or by coupling into maleimide-functionalised surfaces in a chemoselective fashion [19]. For the initial studies two carbohydrate derivatives, 5 and 7, were synthesised. The α-D-mannoside 5 would

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• in a twofold Sonogashira reaction with an excess of phenylacetylene resulted in a chemoselective monoalkynylation of the pseudoanomeric position in quantitative yield (Scheme 2). Even the use of an elevated temperature did not lead to the formation of an enediyne. Further refunctionalization of the

• -Alkynylated glycals were obtained in very good yields whereas the alkynylation in position 2 gave poorer results. Chemoselective reduction of the triple bond in the resulting enyne system by the action of Raney-Ni furnished enol ethers, which could be readily refunctionalized. Methanol proved to be an

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• –carbon bonds [52][53][54], the cleavage of N–O bonds in a chemoselective fashion is also well documented [55][56][57]. The application of samarium diiodide for 1,2-oxazine ring opening allowed efficient syntheses of numerous polyhydroxylated heterocycles, such as pyrrolidine [46], azetidine [47], furan

• transformations of the newly prepared tetrahydro-2H-1,2-oxazines, utilizing samarium diiodide as the key reagent for the chemoselective ring opening, enable a smooth access to novel phenyl-substituted aminopolyols. Their transformation into hydroxylated pyrrolidine derivatives so far proceeds only with moderate

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

• Sarah L. Harding,
• Sebastian M. Marcuccio and
• G. Paul Savage

Beilstein J. Org. Chem. 2012, 8, 606–612, doi:10.3762/bjoc.8.67

• favouring the oxidation of carbon–boron bonds, which makes boronic ester chemistry chemoselective, is a constraint that potentially limits the utility of nitrile oxide cycloadditions in the presence of a boronic acid ester. 4-Formylphenylboronic acid pinacol ester 4 is commercially available or easily

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• oligosaccharide assembly by minimizing or even eliminating additional manipulations between coupling steps, are based either on chemoselective or on selective activation of leaving groups [6]. The use of selective activation [7] offers more flexibility than that of the chemoselective activation which relies on

• distinct orthogonal differentiation of AP and thioglycosides, we next obtained glycosyl acceptor 15 [36] equipped with an ethylthio leaving group. TMSOTf-promoted chemoselective glycosylation between building blocks 1a and 15 produced the expected disaccharide 16 in 71% yield (Table 2, entry 2). In a

• building blocks in oligosaccharide synthesis. Glycosylation of AP glycosyl donors 1a–d. AP glycosides as glycosyl donors and acceptors in chemoselective and selective activations. Supporting Information Supporting Information File 156: Experimental procedures, extended experimental data, 1H and 13C NMR

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• reaction combining an enantioselective organocatalytic Michael addition with the diastereoselective nitro-Mannich/lactamisation cascade. Protodenitration and chemoselective reductive manipulation of the heterocycles was used to install contiguous and fully substituted stereocentres in the synthesis of

• believed that a controlled, chemoselective reduction would offer more options in any synthesis, and thus several commercially available reducing agents were screened in order to achieve selective reduction of only one lactam carbonyl. A notable find was that, by short exposure of denitrated heterocycle 10a

• synthesised in a four-component one-pot cascade combining an enantioselective Michael addition with the diastereoselective nitro-Mannich/lactamisation cascade. Protodenitration and chemoselective reductive manipulation of the heterocycles could be used to install contiguous and fully substituted stereocentres

Synthesis of heteroglycoclusters by using orthogonal chemoselective ligations

• Baptiste Thomas,
• Michele Fiore,
• Isabelle Bossu,
• Pascal Dumy and
• Olivier Renaudet

Beilstein J. Org. Chem. 2012, 8, 421–427, doi:10.3762/bjoc.8.47

• : chemoselective ligation; click chemistry; cyclopeptide; heteroglycocluster; oxime; Introduction Multivalent interactions between carbohydrates and proteins play key roles in diverse biological events, including fertilization, cell–cell communication, host–pathogen interactions, immune response and cancer

• heteroglycoclusters by using a protocol based on orthogonal chemoselective ligations. Two series of compounds containing different combinations of two different sugars have been designed (Figure 1). In one series (heteroglycocluster 2:2), two αMan, αFuc and/or βLac are conjugated at alternate positions into the

• methods, we decided to explore two chemoselective strategies to achieve this purpose. We first selected the oxime ligation since we have previously used this approach successfully for the preparation of sophisticated molecular systems, such as synthetic vaccines [27][28], immunomodulators [29], lectin

Dioxane dibromide mediated bromination of substituted coumarins under solvent-free conditions

• Subrata Kumar Chaudhuri,
• Sanchita Roy and
• Sanjay Bhar

Beilstein J. Org. Chem. 2012, 8, 323–329, doi:10.3762/bjoc.8.35

• in 1e and 1f, vinylic bromination occurred regioselectively to furnish 2e and 2f in high yield without further bromination at C6 and C8, when a stoichiometric amount of DD was used (Table 1, entries 6 and 7). Interestingly, 7-(allyloxy)coumarin (1g) underwent chemoselective addition of bromine across

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• ]. Over the past decade, alternatives for more expeditive, practical and chemoselective arylating technics have arisen, thanks mainly to the great development of novel, stoichiometric and catalytic, direct arylation methodologies (Scheme 1). Thus novel classes of metallating agents resulting from various

• ], manganate ((Me3SiCH2)2Mn(TMP)Li·TMEDA) [3][8], cuprates (MeCu(TMP)(CN)Li2, (TMP)2CuLi) [9][10] and cadmium amides ((TMP)3CdLi) [11][12], for regio- and/or chemoselective deprotonative metalation of aromatics, producing arylmetal intermediates under smooth reaction conditions that are directly suitable for

Ratiometric fluorescent probe for enantioselective detection of D-cysteine in aqueous solution

• Xiao-bo Zhou,
• Wing-Hong Chan,
• Albert W. M. Lee and
• Chi-Chung Yeung

Beilstein J. Org. Chem. 2011, 7, 1508–1515, doi:10.3762/bjoc.7.176

• Cd2+–ACAQ. As cadmium is well-known for its strong affinity to sulfur-containing compounds, we envisioned that the Cd2+-bound ACAQ complex would demonstrate chemoselective binding toward amino acids. Among 22 amino acids, a tripeptide, cysteine derivative and β-mercaptopropionic acid (MPA), only Cys

Access to pyrrolo-pyridines by gold-catalyzed hydroarylation of pyrroles tethered to terminal alkynes

• Elena Borsini,
• Gianluigi Broggini,
• Andrea Fasana,
• Chiara Baldassarri,
• Angelo M. Manzo and
• Alcide D. Perboni

Beilstein J. Org. Chem. 2011, 7, 1468–1474, doi:10.3762/bjoc.7.170

• chemists. Gold catalysis has recently emerged as a suitable way to achieve such a goal, mainly thanks to the chemoselective alkynophilic properties of this attractive metal in different types of reactions [6][7][8][9][10][11][12][13][14][15]. Among the hydroarylation reactions, various kinds of heteroaryl

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• report two protocols recently developed in our laboratories: A chemoselective Negishi cross-coupling protocol tolerating acidic hydrogen atoms. A chemoselective Kumada cross-coupling based on a new radical mechanism. 3.1 Chemoselective Negishi cross-coupling using substrates bearing acidic hydrogen atoms

• -group (Scheme 22) [53][54]. Remarkably, this reaction protocol was extended to substrates bearing an α-aminoester moiety, such as 152 providing the cross-coupling product 153 in 85% yield (Scheme 23 and Supporting Information File 1, Procedure 9) [54]. 3.2 Radical catalyzed Kumada chemoselective cross

• Information File 1. Preparation of polyfunctional heteroarylzinc reagents. LiCl-mediated insertion of zinc dust to aryl and heteroaryl iodides. Selective insertions of Zn in the presence of LiCl. Chemoselective insertion of zinc in the presence of LiCl. Preparation and reactions of benzylic zinc reagents. Ni

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• complexes allowed the preparation of a range of functionalized malonyl esters by direct activation of the allylic alcohol by gold. The methodology appears highly chemoselective toward the allylic lactonization, with the possibility to extend the protocol also to acetate derivatives. Working hypothesis for

Evaluation of a commercial packed bed flow hydrogenator for reaction screening, optimization, and synthesis

• Marian C. Bryan,
• David Wernick,
• Christopher D. Hein,
• James V. Petersen,
• John W. Eschelbach and
• Elizabeth M. Doherty

Beilstein J. Org. Chem. 2011, 7, 1141–1149, doi:10.3762/bjoc.7.132

• conditions [14]. One of the most dramatic results we observed was the complete loss of selectivity in the reduction of an azido group in the presence of an aromatic nitrile (Scheme 1). Initially, the chemoselective reduction of azido nitrile 1 was successfully performed with a 30 mm 10% Pt/C CatCart® to

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• and reductive eliminations). Therefore, platinum(II) and particularly gold(I) or (III) complexes tend to activate alkynes, alkenes or allenes in a highly chemoselective manner; activation that opens interesting reaction pathways that usually involve carbocationic intermediates. Also very important is

• a 3C-atom component in the annulation. A precise explanation for this dichotomy has not been specifically addressed. Cycloadditions initiated by gold-activation of allenes Several gold catalysts can activate allenes in a very chemoselective way, triggering different types of cycloaddition processes

A novel high-yield synthesis of aminoacyl p-nitroanilines and aminoacyl 7-amino-4-methylcoumarins: Important synthons for the synthesis of chromogenic/fluorogenic protease substrates

• Xinghua Wu,
• Yu Chen,
• Herve Aloysius and
• Longqin Hu

Beilstein J. Org. Chem. 2011, 7, 1030–1035, doi:10.3762/bjoc.7.117

• was highly chemoselective, mild, and free of racemization in the coupling step [20]; was compatible with common protecting groups used in peptide chemistry including Fmoc, Boc, Cbz, and Trt; and more importantly, worked very efficiently for electron-deficient aromatic azides substituted with an

Triazole–Au(I) complex as chemoselective catalyst in promoting propargyl ester rearrangements

• Dawei Wang,
• Yanwei Zhang,
• Rong Cai and
• Xiaodong Shi

Beilstein J. Org. Chem. 2011, 7, 1014–1020, doi:10.3762/bjoc.7.115

• also influenced the allene reactivity, probably through gold catalyzed allene activation. The fact that TA–Au gave the dominant (E)-isomers strongly suggests that these complexes may be applied as the chemoselective catalyst in alkyne activation over allene. The reactions of propargyl ester 1a with TA

• -withdrawing groups were suitable for the reaction. Again, no indene by-products were observed in any of the tested cases, even with the electron-enriched p-OMe substituted alkyne 1d. These results highlighted the excellent chemoselective nature of the TA–Au catalyst. The terminal alkyne 1i did not give any

• propargyl ester, carbonate and carbamate 3,3-rearrangement for the synthesis of the corresponding substituted allene derivatives. The chemoselective nature of the TA–Au catalysts was clearly demonstrated, which makes them an interesting class of new catalysts for promoting organic transformations. The

A comparative study of the Au-catalyzed cyclization of hydroxy-substituted allylic alcohols and ethers

• Berenger Biannic,
• Thomas Ghebreghiorgis and
• Aaron Aponick

Beilstein J. Org. Chem. 2011, 7, 802–807, doi:10.3762/bjoc.7.91

• sensitive functional groups. While cyclization reactions of highly elaborated substrates are desirable, mild chemoselective methods are necessary for this endeavor. Homogeneous gold-catalyzed reactions have emerged as a powerful new methodology for the construction of a diverse array of molecular

• architectures; for recent reviews on Au-catalysis, see [2][3][4][5][6][7][8][9][10]. Generally, only mild conditions are necessary and these processes are highly chemoselective. While the typical substrates employed in these reactions effect transformations on alkyne, allene, and alkene moieties, recent reports

• such as benzoyl (16) were unsuitable. This may provide a basis for chemoselective transformations, as allyl esters are readily ionized by Pd0 complexes and the resulting π-allylpalladium species are alkylated by a variety of nucleophiles [27][28]. Finally, 1° allylic and 2° allylic ether substrates

A racemic formal total synthesis of clavukerin A using gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes as the key strategy

• Jae Youp Cheong and
• Young Ho Rhee

Beilstein J. Org. Chem. 2011, 7, 740–743, doi:10.3762/bjoc.7.84

• , extensive attempts at the chemoselective hydrogenation of the trisubstituted olefin 2 gave only compound 1 with poor selectivity. For example, various metal (Pd or Rh)-catalyzed hydrogenations resulted in a mixture of 1 and 3. This problem was also noted in another work on the synthesis of clavukerin A [13

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• chemoselective activation of the cyclopropene, in preference to the alkene, which allows the generation of a gold carbene intermediate. The relative reactivity of cyclopropenes compared to alkynes is an interesting issue that has been addressed by Wang et al. during their studies on the gold-catalyzed

• %). The hydroxyl group did not exert a particular role in this process since 1,2-diphenyl-3-propargylcyclopropene was rearranged to 1,2-diphenylbenzene (97%) under the same conditions [26]. The formation of phenols (and their derivatives) 77–81 could be explained by an initial chemoselective activation of

Gold-catalyzed naphthalene functionalization

• Pedro J. Pérez,
• M. Mar Díaz-Requejo and
• Iván Rivilla

Beilstein J. Org. Chem. 2011, 7, 653–657, doi:10.3762/bjoc.7.77

• are formed quantitatively. The use of the gold analogue also induces the formation of such fused cyclopropanes in addition to the products derived from the formal insertion of the carbene units into the C–H bonds of naphthalene. The system is completely chemoselective with regards to arene

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• products (Scheme 6). These transformations may involve a chemoselective (5-endo-trig versus 7-endo-trig) allenol oxycyclization with concomitant MOM ether deprotection. Taking into account the above results, it was decided to see whether the metal-catalyzed preparation of bicycles 9 can be directly