Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• as sulfate esters and deoxy glycosides have been successfully synthesized. The preactivation-based chemoselective glycosylation is a powerful strategy for oligosaccharide assembly complementing the more traditional premixed method. Keywords: chemoselectivity; glycosides; preactivation; synthesis

• nucleophilically attacks the intermediate forming the desired glycosidic product [22][23][24]. With the preactivation protocol, the donor activation and acceptor glycosylation occur in two distinctive steps. As a result, a unique chemoselectivity can be achieved with preactivation. Glycosyl donors and acceptors

Mechanically induced oxidation of alcohols to aldehydes and ketones in ambient air: Revisiting TEMPO-assisted oxidations

• Andrea Porcheddu,
• Evelina Colacino,
• Giancarlo Cravotto,
• Francesco Delogu and
• Lidia De Luca

Beilstein J. Org. Chem. 2017, 13, 2049–2055, doi:10.3762/bjoc.13.202

• catalyst for the selective oxidation of primary alcohols to aldehydes under ambient aerobic conditions (Scheme 1) [25][26]. The procedure is operationally simple and extremely effective in terms of both chemoselectivity and reaction yield [27][28]. Gao (2016) further improved this methodology by replacing

Chemoselective synthesis of diaryl disulfides via a visible light-mediated coupling of arenediazonium tetrafluoroborates and CS₂

• Jing Leng,
• Shi-Meng Wang and
• Hua-Li Qin

Beilstein J. Org. Chem. 2017, 13, 903–909, doi:10.3762/bjoc.13.91

• tetrafluoroborates; carbon disulfide; chemoselectivity; diaryl disulfides; photocatalyst; Findings The development of methods for the functionalization of peptides and proteins under mild conditions is a current frontier in the fields of chemistry, biology and drug discovery [1][2][3][4]. Most of the

• pharmaceutically relevant proteins contain disulfide bonds, furthermore, the disulfide ligation and its established chemoselectivity is of great advantage for proteins’ functionalization [5]. In addition, disulfides also play valuable roles as versatile building blocks for industrial applications [6][7][8]. Thus

• (Table 1, entries 7 and 8). Unfortunately, under the applied conditions, the chemoselectivity of the reaction was poor, affording a mixture of unexpected diphenyl sulfide (4a) and diphenyl polysulfides (5a) as byproducts. Thus, a study to optimize the reaction conditions with regard to chemoselectivity

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• issues owing to many potential side reactions, particularly in relation to chemoselectivity, i.e., over-hydrogenation of alkenes to alkanes [44][45], resistance of other functional groups (ketones [46][47], amines [48][49], azides [50]), regioselectivity [51][52] , isomerization [53][54] and

• in the absence of theoretical or mechanistic studies. Phenylacetylene (7), 1-bromo-4-ethynyl benzene (8) and 1-ethynyl-4-nitrobenzene (9) were hydrogenated using a Pd@C catalyst with trimodal pore-size distribution [152]. The chemoselectivity to the corresponding alkene product showed to follow the

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• ., boron salts from reductive amination [4]. Hydrogenation offers a greener approach but is often only applicable to simple substrates due to chemoselectivity issues. An approach that has received much attention recently is the concept of hydrogen borrowing catalysis [5][6][7][8][9][10][11][12][13][14][15

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

• Arno Verlee,
• Thomas Heugebaert,
• Tom van der Meer,
• Pavel I. Kerchev,
• Frank Van Breusegem and
• Christian V. Stevens

Beilstein J. Org. Chem. 2017, 13, 303–312, doi:10.3762/bjoc.13.33

• one single step. Furthermore, acid chlorides show a high reactivity [21] making m-(chlorosulfonyl)benzoyl chloride an ideal starting material as was shown by Yang et al. [18]. By transferring this reaction to a multistep flow set-up, we envisioned an improved chemoselectivity. This phenomenon is not

• ][24][25][26], resulting in an improved chemoselectivity. Furthermore, the use of an automated process leads to the possibility to produce libraries of compounds in a fast manner. In addition, an alternate biocompatible and water miscible solvent would result in a flexible and automated chemoselective

• potential of a chemoselective synthesis as a continuous process. As bench mark, aniline and azepane were used as first and second reagent, respectively. After addition of the first reactant and completion of the reaction (followed by TLC) the second reactant was added. The chemoselectivity was determined by

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• benzoylated thioglycosides with high chemoselectivity and was therefore used in a range of high yielding oligosaccharide syntheses [38]. The bifunctional silicon protective group DTBS (Figure 1) has been used both to increase and decrease the reactivity of glycosyl donors. The 4,6-O-DTBS-protected

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• activated by mechanochemical energy [12]. The yields, reaction rates and chemoselectivity obtained in the presence of melted PEGs were compared with the results obtained in dry-grinding conditions. Results and Discussion H-Leu-OMe was used as benchmark for the mechanochemical preparation of 3-ethyl-5

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

• Anna Zaghi,
• Daniele Ragno,
• Graziano Di Carmine,
• Carmela De Risi,
• Olga Bortolini,
• Pier Paolo Giovannini,
• Giancarlo Fantin and
• Alessandro Massi

Beilstein J. Org. Chem. 2016, 12, 2719–2730, doi:10.3762/bjoc.12.268

• . Moreover, the disclosed flow procedure constituted an equally effective (complete chemoselectivity) and environmentally benign alternative to the analogous batch process towards benzoin- and Stetter-type products mediated by toxic cyanide anions [29][30]. Results and Discussion The possibility of

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• synthetically relevant intermediates (precursors of baclofen and boscalid). Keywords: chemoselectivity; continuous processes; flow synthesis; nitro reduction; trichlorosilane; Introduction The reduction of nitro compounds to amines is a fundamental transformation in organic synthesis. The nitration of

• demonstrated. The use of extremely inexpensive and non-hazardous chemicals, the very high chemoselectivity and the possibility to realize a completely automated reduction/work-up/isolation process are distinctive features that make the protocol suitable for the reduction of a large variety of products and

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• chemoselectivity and thus the moderate yield. When the H-bond donor was changed from thiourea to urea (catalyst II), it did not provide better results (Table 1, entry 2) [17][19]. In the [4 + 2] annulation of 5H-thiazol-4-ones with nitroalkenes, dipeptide-based thiourea−amide−tertiary amine III (DP-TAA) was

• ). To improve the chemoselectivity, we synthesized a series of DP-UAAs through tuning of the substituent groups of the urea. We were pleased to find that the reaction rate could be tremendously increased by utilizing DP-UAA V as the catalyst, and 3a was obtainable with high enantioselectivity, high

• chemoselectivity and excellent yield of 98% (Table 1, entry 10). With the optimal reaction conditions in hand, we examined the substrate scope of the enantioselective [4 + 2] cycloaddition between 5H-thiazol-4-ones 1 and N-itaconimides 2, catalyzed by DP-UAA V (Scheme 1). Firstly, with 1a as the model 5H-thiazol-4

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• diastereoisomeric THF diols in 67% yield (only major isomer 58b shown in Scheme 13). It is worth noting that this oxidative cyclization proceeded with high chemoselectivity leaving the remote C–C-double bond unreacted. For the formation of the adjacent THF ring different and stereodivergent strategies were studied

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• group. Further, the yields of products varied from high to moderate, depending upon the reaction time due to the competitive decomposition of the nitroso species, reducing the yield. The chemoselectivity of this system also depends on the reactivity of the hydroxamic acid: the higher the reactivity, the

• lower the chemoselectivity. Moreover, DFT calculations of this type of reaction confirmed the preference for endo transition states. These calculations showed that the acylnitroso species are superreactive, and the activation energies are lower than the isomerization barriers between some cis and trans

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• reduced with dimethyl phosphonate [16][17]. While the mechanism of this Hirao reduction is not fully understood, the reaction was exquisitely mild and proceeded with high chemoselectivity for the geminal dihalide, delivering (−)-anverene (1) in high yield as a 7:1 mixture of E/Z isomers. Following

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• - and monoacetal whatever the conditions, as a new example of the lack of chemoselectivity of this long polyisoprenyl chain derivatives. The differentiation of both ends of squalene was thus performed starting from trisnorsqualenaldehyde 10. Protection of 10 as 2,2-dimethyl-1,3-dioxane derivative gave

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• determined by single X-ray crystallographic analysis of rac-14 (see Supporting Information File 1) and revealed that the major diastereomer 13 indeed possessed the necessary stereochemical configuration [21] for accessing keramaphidin B, assuming the chemoselectivity of the nitro-Mannich lactamisation

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• chemoselectivity [57] of this transformation. In 2011, Davies et al reported a chiral rhodium complex based on a new cyclopropylcarboxylate ligand (Scheme 16) [58]. Among the various transformations promoted by this new catalyst we can find enantioselective carbenoid insertion into the endocyclic allylic C(sp3)–H

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• substituted arene rings. An elegant approach to variously arylated pentaarylpyridines was recently proposed by Reimann et al. [60]. The final outcome of such a procedure is governed by many factors, including differences in site reactivity of polyhaloarenes (concerning both regio- and chemoselectivity

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• basic medium and homo-benzoin products are often isolated as byproducts in other NHC-mediated reactions of aldehydes. The absence of chemoselectivity issues makes homo-benzoin reactions less challenging when compared to the cross-benzoin variant. NHC-mediated aerial oxidation of aldehydes to the

• ). The NHC-catalysed chemoselective intermolecular cross-benzoin condensation reaction of aromatic and aliphatic aldehydes was reported by Yang and co-workers. The chemoselectivity was achieved by using a large excess of the aliphatic aldehyde (molar ratio of 1:15) [25]. Thus, directing groups on the

• without affecting the yield of product and chemoselectivity (Scheme 11). Morpholinone and piperidinone-derived triazolium precatalysts can catalyze highly chemoselectively the cross-benzoin reaction of aliphatic and aromatic aldehydes [26]. Smooth and selective benzoin reactions were observed with a wide

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• Cu catalysis were obtained after 24 h, CuI was selected for this purpose. The reasoning behind this is reflected in the chemoselectivity experiments (vide infra), where it was shown that CuI is a slightly more potent catalyst than FeCl2·4H2O. Additionally, comparison of the reaction rate for both

• high temperatures the authors switched to propylene carbonate as the solvent. Chemoselectivity When multiple activated methylene motifs are present the chemoselective oxidation of one of these positions can be achieved as we previously exemplified for 2-methyl-6-(4-methylbenzyl)pyridine (18b, Table 5

• -tolyl)methanone (19a) in 57% yield (Table 5, entry 2). A similar chemoselectivity was observed for the oxidation of 18b where Cu catalysis lead to bis-oxidation (20b, Table 5, entry 4) while Fe catalysis resulted in mono-oxidation (19b, Table 5, entry 5). When the reaction with 18a using Cu catalysis is

Recent advances in metathesis-derived polymers containing transition metals in the side chain

• Ileana Dragutan,
• Valerian Dragutan,
• Bogdan C. Simionescu,
• Albert Demonceau and
• Helmut Fischer

Beilstein J. Org. Chem. 2015, 11, 2747–2762, doi:10.3762/bjoc.11.296

• synthetic strategies ensure metal incorporation from the corresponding metal-containing monomers into the polymer in a precise, predetermined mode. With the advent of new metathesis catalysts endowed with a high activity and chemoselectivity and good tolerance towards many functionalities [28][29][30], ROMP

Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism

• David Porter,
• Belinda M.-L. Poon and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 2549–2556, doi:10.3762/bjoc.11.275

• chemoselectivity profiles that are consistent with reaction via nitroso–ene mechanisms [35][36][38][41]. Thus we hypothesised that the hydroxyamination reactions mediated by FeTPA (4) and FeBPMEN (5) follow a similar mechanism: iron-catalysed oxidation of 8 to generate the N-Boc-nitroso intermediate 13, which then

Copper-catalyzed arylation of alkyl halides with arylaluminum reagents

• Bijay Shrestha and
• Ramesh Giri

Beilstein J. Org. Chem. 2015, 11, 2400–2407, doi:10.3762/bjoc.11.261

• catalyzed by Pd and Ni, exploit a wide range of organometallic reagents of Mg, Zr, Zn, Sn, Al, B, Si and In as sources of nucleophiles. Among these metals/non-metals, Al offers a unique feature due to its high chemoselectivity and Lewis acidity [10][11][12]. In addition, Al also has low toxicity and is an

Synthesis of α,β-unsaturated esters via a chemo-enzymatic chain elongation approach by combining carboxylic acid reduction and Wittig reaction

• Yitao Duan,
• Peiyuan Yao,
• Yuncheng Du,
• Jinhui Feng,
• Qiaqing Wu and
• Dunming Zhu

Beilstein J. Org. Chem. 2015, 11, 2245–2251, doi:10.3762/bjoc.11.243

• to the sterically hindered effect of the α-methyl substitution, which is consistent with the results for Pyrococcus furiosus (whole-cell) [36] and NiCAR [31]. However, no significant difference was noted between 3-phenylbutyric acid (15a) and 7a. Mycobacterium CAR showed good chemoselectivity for the

Stereochemistry of ring-opening/cross metathesis reactions of exo- and endo-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitriles with allyl alcohol and allyl acetate

• Piotr Wałejko,
• Michał Dąbrowski,
• Lech Szczepaniak,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 1893–1901, doi:10.3762/bjoc.11.204

• allyl alcohol and allyl acetate may be partially stereocontrolled by a proper choice of the reaction catalyst. However, the regioselectivity largely depends on the starting material structures. Unexpectedly, the chemoselectivity of the ROCM product formation in competition with the undesired ROMP