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

• ), 4.11–4.13 (m, 4H, 5-H, 9-H, NCH2), 4.58 (dd, J = 4.5, 8.1 Hz, 1H, 4-H), 7.26–7.29 (m, 5H, Ph) ppm; ESI-TOF (m/z): [M + H]+ calcd for C23H38NO5Si, 436.2514; found, 436.2553. The analytical data are in accordance with literature [23][37]. Typical procedure for ketone reduction with NaBH4 (procedure 3

• ) (1S,4S,5S,6R,10S)-7-Benzyl-5-(tert-butyldimethylsiloxy)-4-(hydroxymethyl)-2,2-dimethyl-3,8-dioxa-7-azabicyclo[4.3.1]decan-10-ol: Under argon atmosphere ketone 11 (703 mg, 1.61 mmol) was dissolved in dry EtOH (26 mL). The solution was cooled to 0 °C and NaBH4 (119 mg, 3.15 mmol) was added in portions

• of the carbonyl group and deprotection. Conditions: a) NaBH4, EtOH, 0 °C, 40 min to 16 h; b) TBAF (1 M THF), THF, 0 °C, 10 min to 3.5 h. [TBAF = tetra-n-butylammonium fluoride] Synthesis of propargylic ether 18. Conditions: a) propargyl bromide, NaOH, TBAI, H2O/CH2Cl2, −20 °C → rt, 7 d; b) NaBH4

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• polarity of 10) to give the pure final product. Synthesis of benzyl azides. a) BnBr, K2CO3, acetone or DMF, rt or 60 °C (for 2d); b) 1) MsCl, Et3N, CH2Cl2, −10 °C; 2) NaN3, DMF, rt; c) NaBH4, MeOH, rt; d) PhB(OH)2, Cs2CO3, Pd(OAc)2, PPh3, 80 °C, 4.5 h; e) 1) MeOH, H2SO4, reflux; 2) LiAlH4, THF, rt

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

• regioselective opening [60][61] leading to the β-hydroxyketone that was temporarily masked as a TES ether. Reduction of ketone 85 with NaBH4 resulted in the formation of two diastereomeric alcohols in 2:1 ratio. To our delight flash chromatography permitted smooth separation of the two compounds. nOe studies

• . Reagents and conditions: a) CSA, 2,3-butanedione, trimethyl orthoformate, MeOH, reflux, 16 h, 93%; b) NaBH4, MeOH, rt, 0.5 h, quant.; c) silica-gel supported NaIO4, CH2Cl2/MeOH (20:1), rt, 3 h, quant.; d) MsCl, NEt3, CH2Cl2, 0 °C to rt, 3 h, quant.; e) paraformaldehyde, imidazole, THF/1 M NaHCO3 (1:1), rt

• , 2.5 h, 74%; f) TBSOTf, 2,6-lutidine, CH2Cl2, 0 °C, 15 min, quant.; g) LiHMDS, MeI, THF/DMPU (5:1), −78 °C to −10 °C, 91%, de = 100%; h) NaBH4, CeCl3·7H2O, MeOH, 0 °C, 15 min, 90%, de = 100%; i) PPh3, p-nitrobenzoic acid, DEAD, toluene, rt, 18 h; j) MeOH, Et2O, aqueous saturated K2CO3 solution, rt, 1 h

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• acid was converted to the corresponding anhydride, which could be reduced to the alcohol using NaBH4, followed by reoxidation with DMP to yield aldehyde 154. Attachment of furanone enolate 155 [134][135], followed by reoxidation yielded tricycle 156. Deprotection of the amine and the MOM-protected

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

• start with the same for the synthesis of dasyclamide (6). As explained in Scheme 5 attempts to get enamide 22 by reductive dehydroxylation of compound (±)-18 using NaBH4/CuCl2·2H2O or Al-NiCl2·2H2O [16][17][18] and reductive deacetoxylation of compound (±)-21 using NaBH4/t-BuOH or LiBEt3H, THF [19][20

• ][21] did not yield fruitful results. These failures pushed us to explore the dehydroxylation or deacetoxylation reaction using a simpler precursor (±)-16. However, attempts to dehydroxylate the Baylis–Hillman adduct (±)-16 with NaBH4/CuCl2·2H2O [17] and Al-NiCl2·2H2O proved unsuccessful hence, we

• focused on the deacetoxylation of (±)-16. Treatment of (±)-16 with acetyl chloride in the presence of pyridine afforded the corresponding acetate (±)-23 in almost quantitative yield, which underwent the desired deacetoxylation with NaBH4/t-butanol [20] to provide the ester 24 in good yield (Scheme 6). The

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• NaBH4 in an alkaline medium [331]. 3.6. Synthesis of 1,2-dioxanes from 1,4-dicarbonyl compounds The reaction of 1,4-diketones 242 (cyclohexanone derivatives) with hydrogen peroxide in a neutral medium produced 3,6-dihydroxydioxanes 243 albeit without reported yields (Scheme 69). The resulting compounds

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

• reduction can be used. The ester can be reduced to alcohol 6 (e.g., with NaBH4/LiCl) and then oxidized to 1 with non-basic methods (e.g., IBX/DMP [30] or TEMPO/NaOCl [31] to name a few), which will not epimerize the α-center. For our synthesis of 1, we adopted a slightly modified sequence [32]. L-Serine (2

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

• discouraging results we did not pursue enantioselective reduction methods further to establish the required 9R-configuration, but considered a resolution approach. Ketone 14 was first reduced with NaBH4 to the expected diastereomeric mixture of alcohols 18, which were then subjected to the conditions of the

• starting point for this approach (Scheme 5). Compound 21 was obtained via two alternate routes, either by reduction of ketone 13 (Scheme 3) with NaBH4 or from ester 25 via one-flask reduction to the corresponding aldehyde and addition of methylmagnesium chloride. Ester 25 was in turn synthesized in three

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• relevant examples of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives. Reagents and conditions: (a) CF3COOH, anhydrous dichloromethane, reflux; (b) NaBH4, MeOH. Optimization of the reaction conditions for the Cu-catalyzed synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline (2a).a Synthesis of 5,6-dihydroindolo

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• -trifluoromethylisoxazoles were easily prepared from trifluoromethyl aldoxime 2 under mild conditions by using DIB as oxidant. Theoretical studies of the reactivity of trifluoroacetonitrile oxide 4 toward olefins and alkynes were carried out. The 3-trifluoromethyl-2-isoxazolines were ring-opened with NaBH4 and NiCl2 to

• utilizing H2 and Raney-Ni as catalysts was described by Tanaka and co-workers [49]. However, this methodology is restricted to the synthesis of N-methylated amino alcohols. Instead we investigated the reduction and the ring opening of 3-trifluoromethyl-2-isoxazolines 1a and 1b in the presence of NaBH4 and

• different fluorinated building blocks was demonstrated by the easy ring opening of these intermediates with NaBH4 and NiCl2, yielding the corresponding trifluoromethylated γ-amino alcohol. Example of bioactive molecules bearing the 2-isoxazoline nucleus. Dimerization and isomerization products from nitrile

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• ), 45 °C, 1.5 h, 78%, (k) NaBH4, EtOH, 65 °C, 5 d, 62%. Synthesis of 20-demethyl-bis-exo-cyclopamine 19 and F-nor-20,25-bis-demethyl-exo-cyclopamine 23. Reaction conditions: (a) allylcerium chloride, THF, 0 °C, 30 min, 93%; (b) 9-BBN, THF, 70 °C, 6 h; then NaBO3, 50 °C, 12 h, 91%; (c) BAIB, TEMPO

Bis(benzylamine) monomers: One-pot preparation and application in dendrimer scaffolds for removing pyrene from aqueous environments

• Olivia N. Monaco,
• Sarah C. Tomas,
• Meghan K. Kirrane and
• Amy M. Balija

Beilstein J. Org. Chem. 2013, 9, 2320–2327, doi:10.3762/bjoc.9.266

• temperatures hindered the ability to cleanly obtain bisimines 3. Alternatively, the condensation of 3,5-diamino benzoic acid with 2.1 equiv of benzaldehyde (2a) in methanol at room temperature followed by in-situ reduction with NaBH4 and acidification with 2 N HCl resulted in the precipitation of bisamine 4a

• ]. Replacing NaBH4 with other hydride sources such as NaBH3CN did not impact the reduction rate of 4f. To ensure a clean isolation of bisamines 4, the benzaldehyde starting material needed to be free from oxidized aldehyde byproducts. Using elevated temperatures to promote the formation of bisamines 4 was

• bisamine functionalities and result in increased compound stability. Structure 7 was successfully prepared through a multi-step synthetic scheme [21]. Condensation of 1 with 2.1 equivalents of benzaldehyde 7 followed by in situ reduction with NaBH4 and acidification with 2 N HCl provided dendron 8 (Scheme

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• ), MgSO4 (2.0 equiv), THF, rt. 2. NaBH4 (2.0 equiv), MeOH, rt; (b) ethyl malonyl chloride (1.05 equiv), Et3N (1.2 equiv), CH2Cl2, rt; (c) KOt-Bu (1.1 equiv), THF, reflux; (d) amine (1.0 equiv), toluene, reflux; (e) butyl chloroformate (1.2 equiv), DMAP (2.2 equiv), CH2Cl2, rt. Synthesis of C(5)-alkyl 3

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• triethylsilane and BF3·Et2O [53], affording 11. Oxidative cleavage of 11 with KMnO4/Bu4NBr [54] afforded iso-C12 acid 1. Alternatively, anti-Markovnikov hydration of 11, using I2/NaBH4 then hydrogen peroxide [55], afforded the alcohol 12, and oxidation of 12 with KMnO4/Bu4NBr afforded iso-C13 acid 2

• ). Reagents and conditions: (a) MeMgBr, THF, 98%; (b) BF3·Et2O, Et3SiH, CH2Cl2, 99%; (c) KMnO4, Bu4NBr, AcOH, H2O, 88% for 1, 96% for 2; (d) i) I2, NaBH4, THF, ii) H2O2, 95%; (e) MsCl, Et3N, CH2Cl2, 98%; (f) KCN, DMSO, THF, 72%; (g) aq NaOH, EtOH, 96%. Synthesis of iso-C15 4, iso-C16 5, and iso-C17 6 fatty

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• bond oxidation with 3-chloroperbenzoic acid (MCPBA) to afford epoxy amino ester 6 cis-diastereoselectively [57] (Scheme 1). Opening of the oxirane ring in 6 with NaBH4 in EtOH at 70 °C proceeded regioselectively, providing exclusively amino ester 5 with the hydroxy function on position 4 (for analogous

Simple and rapid hydrogenation of p-nitrophenol with aqueous formic acid in catalytic flow reactors

• Rahat Javaid,
• Shin-ichiro Kawasaki,
• Akira Suzuki and
• Toshishige M. Suzuki

Beilstein J. Org. Chem. 2013, 9, 1156–1163, doi:10.3762/bjoc.9.129

• of the commercial importance of p-aminophenol, improvement of catalytic performance was attempted by using nanoparticles (NPs) of Au, Pd, and Ni immobilized on various solid supports. Apart from the use of gaseous H2, the reduction of p-nitrophenol with sodium borohydride (NaBH4) was studied

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• dithioketal 14 (86% yield) [72][73][74]. Wittig olefination of the C-1 ketone with methoxymethylenetriphenylphosphine [75] yielded the corresponding enol methyl ether, which was hydrolyzed to the aldehyde under acidic conditions and reduced with NaBH4 to form alcohol 15 with desired diastereoselectivity at

3D-printed devices for continuous-flow organic chemistry

• Vincenza Dragone,
• Victor Sans,
• Mali H. Rosnes,
• Philip J. Kitson and
• Leroy Cronin

Beilstein J. Org. Chem. 2013, 9, 951–959, doi:10.3762/bjoc.9.109

• this range of concentrations when using conventional reducing agents, such as NaBH4. Using this methodology, imines 3a–d were reduced affording the corresponding secondary amines 4a–d (Table 4). The reactions were followed by monitoring the absence of the imine and aldehyde bands in the in-line ATR-IR

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• was observed in the reaction medium essayed. Finally, the chiral 1,3-nitroamines 9a,b were easily transformed into the desired chiral 1,3-diamines 14a,b (80% yield) by treatment with NaBH4, NiCl2·6H2O in MeOH [87] (Scheme 2). Conclusion An efficient, reproducible and versatile approach for the

• equiv), CH3NO2, THFdry, rt, 4 h (91–95%). (v) (a) MsCl, CH2Cl2, −78 °C, then TEA 60 min, rt (95–99 %). Synthesis of 1,3-diamines 14a,b. (i) NaBH4/NiCl2·6H2O/MeOH/3 h/rt. Reactivity of 2a–c with different nucleophiles. Supporting Information Supporting Information File 5: General information

Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

• Benito Alcaide,
• Pedro Almendros,
• M. Teresa Quirós and
• Israel Fernández

Beilstein J. Org. Chem. 2013, 9, 818–826, doi:10.3762/bjoc.9.93

• /def2-SVP//B3LYP/def2-SVP level. Preparation of allenic carbamates 2a–j. Reagents and conditions: (i) Propargylamine, MgSO4, CH2Cl2, rt, 15 h. (ii) NaBH4, MeOH, rt, 0.5 h. (iii) Boc2O, Et3N, CH2Cl2, rt, 2–15 h. (iv) (CH2O)n, iPr2NH, CuBr, 1,4-dioxane, reflux, 1 h. (v) Ohira–Bestmann reagent, K2CO3, MeOH

Reductions of aldehydes and ketones with a readily available N-heterocyclic carbene borane and acetic acid

• Vladimir Lamm,
• Xiangcheng Pan,
• Tsuyoshi Taniguchi and
• Dennis P. Curran

Beilstein J. Org. Chem. 2013, 9, 675–680, doi:10.3762/bjoc.9.76

• for such reductions, boron reductants are widely used in the field of synthetic chemistry due to their availability and favorable reaction profiles [1][2][3]. For instance, sodium borohydride (NaBH4) is an inexpensive salt that is one of the most popular hydride sources for the reduction of aldehydes

• and ketones [4]. Reactions with NaBH4 are usually performed in a protic solvent such as methanol, and quenching and aqueous workup are essential steps along the way to isolation of the product. Although many borohydride reagents are relatively stable solids, their contact with moisture can cause

• acid functions as a Brønsted acid to activate the carbonyl group towards attachment by 1. This is different from NaBH4, which reacts quickly with acetic acid to liberate H2 and form a modified reducing agent, NaBH(OAc)3 [21][22]. Even with heating, the direct acid/base reaction of 2 and acetic acid was

Synthesis of meso-substituted dihydro-1,3-oxazinoporphyrins

• Satyasheel Sharma and
• Mahendra Nath

Beilstein J. Org. Chem. 2013, 9, 496–502, doi:10.3762/bjoc.9.53

• NaBH4 in a chloroform/methanol mixture at 25 °C produced meso-substituted aminoporphyrins 4 and 5, respectively. In the final step, these aminoporphyrins underwent a condensation cyclization reaction with aldehydes in THF under reflux to form new dihydro-1,3-benzoxazinoporphyrins 6–9 in good yields

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

• acetophenone derivatives 7 to give the corresponding chalcones of type 9 in 66–85% yields. Contrary to Xue’s reduction method where H2/Pd was used, we used NaBH4 in the reduction of both the carbon–carbon and carbon–oxygen double bonds of chalcone derivatives 9 to give the corresponding alcohols 17. It is

• noteworthy that the carbon–carbon double bond was also reduced by NaBH4, a reagent usually used for the reduction of carbonyl groups. Cyclization was achieved by heating intermediates 17 under reflux in acetic acid to give the corresponding flavans of type 10 in 62–87% yields (Scheme 4). Recently, Sashidhara

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• two novel linkers on different resins. Synthesis of a new acylsulfonamide safety-catch linker. Reagents and conditions: (a) benzaldehyde, Na2SO4, DCM; (b) NaBH4, EtOH; 82% over two steps; (c) H2, 10% Pd/C, EtOH, DIPEA; (d) cat. H2SO4, MeOH, 88% over two steps; (e) DSC, Et3N, DCM/CH3CN, 85%; (f) DHP, p

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• the challenging 1,4-reduction of flavones 60 with NaBH4 (Scheme 19). It was shown that under photochemical reduction conditions a number of products, including ethyl salicylate and various dimers, were formed. Use of a photochemical flow system rather than a batch reactor was found to give a greater