Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• the oxidative cyanation of tertiary amines using Ru as the catalyst (Scheme 11) [35]. In this reaction, the comparatively safer acetone cyanohydrin was utilized as the cyanating agent. Better yields of products were obtained for both electron-rich and electron-deficient tertiary amines. Cyclic amines

• such as piperidine, tetrahydroisoquinoline derivatives, and pyrrolidine were also tolerated well in this reaction. The use of the non-toxic and inexpensive acetone cyanohydrin makes this method more advantageous compared to the known methods. 2 Cyanation of arenes and heteroarenes 2.1 Cyanation of

• complexes. From our discussion it is evident that the most commonly used cyanating reagents include highly toxic compounds such as K4[Fe(CN)6], NaCN, CuCN, TMSCN etc. However, some of the reported works involve the use of safer and greener cyanation sources like NCTS, acetone cyanohydrin, ethyl cyanoformate

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

• Man-Man Wang,
• Hao Huang,
• Lei Shu,
• Jian-Min Liu,
• Jian-Qiu Zhang,
• Yi-Le Yan and
• Da-Yong Zhang

Beilstein J. Org. Chem. 2020, 16, 233–247, doi:10.3762/bjoc.16.25

• , DCM, rt; (e) substituted 1,3-dimethyl-1H-pyrazol-5-ol, EDCI, DMAP, DCM, rt; (f) Et3N, acetone cyanohydrin, DCM, rt. Synthetic route of the title compound III. Reagents and conditions: (a) methyl chloroacetate, K2CO3, CH3CN, 65 °C; (b) K2CO3, H2O, 65 °C; (c) aqueous HCl solution (10%), rt; (d

• ) substituted 1,3-cyclohexanediones, EDCI, DMAP, DCM, rt; (e) substituted 1,3-dimethyl-1H-pyrazol-5-ol, EDCI, DMAP, DCM, rt; (f) Et3N, acetone cyanohydrin, DCM, rt. Synthetic route of the title compounds II. Reagents and conditions: (a) NaOH, TBAB, H2O, 100 °C; (b) concentrated HCl solution, rt; (c) methyl

• chloroacetate, K2CO3, CH3CN, 65 °C; (d) K2CO3, H2O, 65 °C; (e) aqueous HCl solution (10%), rt; (f) substituted 1,3-cyclohexanediones, EDCI, DMAP, DCM, rt; (g) substituted 1,3-dimethyl-1H-pyrazol-5-ol, EDCI, DMAP, DCM, rt; (h) Et3N, acetone cyanohydrin, DCM, rt. Chemical structures of title compound I and their

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• chloride in THF [30]. Initially, the trimethylsilyl cyanohydrin 16 was subjected to solvolysis in ethanol with aqueous sulfuric acid. Unfortunately, those conditions resulted in displacement of the 4-chloro substituent with ethanol giving the 4-ethyl ether 17 in 35% yield. To circumvent this undesired

• substitution at the 4-position, the cyanohydrin 16 was hydrolyzed by a two-step process. First, hydrogen chloride in ethanol (3.3 molar) was used to produce the imidate 18 in quantitative yield. The structure of 18 was verified by NMR to prove that the 4-position had not suffered displacement by ethanol

• cyanohydrin-hydrolysis route (10f→19) and an umpolung acyl addition strategy (10f→21). The development of a library of quinoline scaffolds is currently underway within our lab utilizing this synthetic process [34][35]. Experimental General procedure for isatoic anhydride synthesis 6-Bromo-2H-benzo[d][1,3

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

•  3). For the synthesis of 25, we started from the known limonene oxide-derived diol 20 [24] that was hydrogenated, oxidized, and silylated at the tertiary alcohol moiety (81%). Reaction of deprotonated 21 with ethyl cyanoformate afforded cyanohydrin 22 by attack of liberated cyanide at the carbonyl

• carbon following the ethoxycarbonylation. The 3JHH coupling constant proved that the isopropyl and ethoxycarbonyl groups both assume an equatorial position in a chair conformation. We were not able to obtain an X-ray analysis of cyanohydrin 22, but of one diastereomer (30) of an analog where the OTBS was

• replaced by a methoxy group (Scheme 4, obtained by ethoxycarbonylation of 28) [25]. In agreement with the NMR data, cyanohydrin 30 adopts a chair conformation in the crystal. The 1H NMR spectra of diastereomers 29 and 30 differ characteristically regarding the chemical shift of the hydroxy proton which

Visible light photoredox-catalyzed deoxygenation of alcohols

• Daniel Rackl,
• Viktor Kais,
• Peter Kreitmeier and
• Oliver Reiser

Beilstein J. Org. Chem. 2014, 10, 2157–2165, doi:10.3762/bjoc.10.223

• benzylic alcohols, α-hydroxycarbonyl, and α-cyanohydrin compounds. Moreover, the selective catalytic monoacylation of diols is possible, thus allowing efficient monodeoxygenations as exemplified in the conversion of (+)-diethyl tartrate to unnatural (+)-diethyl malate. Results and Discussion Following the

• could be reduced again and defunctionalized materials were isolated in moderate to good yields (Table 3, entries 10 and 11). Bis(trifluoromethyl)benzoic acid 5 could easily be recovered (>90%) in an acid–base extraction step. Also bis(trifluoromethyl)benzoates of non-benzylic α-cyanohydrin 6a and α

• microreactor (see Supporting Information File 1). Conclusion In summary a protocol for the deoxygenation of benzylic alcohols, α-hydroxycarbonyl and α-cyanohydrin compounds under visible light photocatalysis was developed using 3,5-bis(trifluoromethyl)benzoic anhydride for alcohol activation. Since 3,5-bis

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

• of silyl enol ether 188 furnished the desired cis-divinylcyclopropane, which underwent smooth DVCPR under mild conditions to give bridged bicycle 189. The alcohol was deprotected and oxidized to aldehyde 190. The aldehyde was transferred into the corresponding cyanohydrin trimethylsilyl ether using

One-pot synthesis of cyanohydrin derivatives from alkyl bromides via incorporation of two one-carbon components by consecutive radical/ionic reactions

• Shuhei Sumino,
• Akira Fusano,
• Hiroyuki Okai,
• Takahide Fukuyama and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2014, 10, 150–154, doi:10.3762/bjoc.10.12

• bromides and nucleophilic addition of a cyanide ion was investigated, which gave moderate to good yields of cyanohydrin derivatives in one-pot. Keywords: alkyl bromide; carbon monoxide; cyanohydrin; ethyl cyanoformate; multicomponent; radical reaction; Introduction Radical carbonylation reactions have

• ). During the course of our study on borohydride-mediated radical hydroxymethylation of alkyl halides with CO, we found that cyanohydrin was obtained as a byproduct when Bu4NBH3CN was used as a radical mediator [15], which led us to investigate the one-pot synthesis of cyanohydrins based on radical

• ]. The common method to obtain cyanohydrins is the reaction of aldehydes with a cyanide sources such as TMSCN [22][23], ethyl cyanoformate [24][25][26] or acyl cyanide [27][28]. We provide here an efficient one-pot method for the synthesis of cyanohydrin derivatives via consecutive radical/ionic C–C bond

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

• linear fashion starting by amination of acetone cyanohydrin (3.19) followed by CBz-protection of the resulting amine and finally aminolysis of the nitrile 3.20 with hydroxylamine [90] (Scheme 34). The resulting amidoxime 3.21 was then reacted with dimethylacetylene dicarboxylate (DMAD) which upon heating

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• demonstrated to be a competent substrate for the nickel(0)-catalyzed coupling with a model epoxide. Several synthetic approaches toward the C10−C26 epoxide have been pursued. The C13 stereocenter can be set by allylation and reductive decyanation of a cyanohydrin acetonide. A mild, fluoride-promoted

• stereoselective fashion from displacement of a leaving group at C10, a means for the selective formation of a syn-1,3-diol at C11 and C13 is required. Rychnovsky has demonstrated that alkylation of 4-cyano-1,3-dioxanes (cyanohydrin acetonides) constitutes a practical and valuable approach to syn-1,3-diol

• synthesis [66]. The lithiated cyanohydrin acetonides react as nucleophiles with alkyl, allyl, and propargyl halides, as well as with epoxides. Although the alkylation itself is highly stereoselective in favor of the axial nitrile, the syn-1,3-diol stereochemistry is ultimately set in a subsequent reductive

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• cyanohydrin reaction procedure. Results and Discussion C-Elongation In an initial C-elongation attempt, with the aim to avoid HCN as C-synthon, we decided to follow a protocol employing sodium cyanide, as described by Hudson [29] (Scheme 2). By this reaction sequence, starting from aldohexose 1, the obtained

• resulting cyanohydrin to aldonolactone 9 was accomplished by treatment with strong acidic ion-exchange resin IR-120 H+. In contrast to the described reduction employing sodium amalgam, we preferred sodium borohydride, which has been reported as a suitable agent for the reduction of lactones to the

• . These unsatisfactory results caused us to change the strategy for the C-elongation reaction sequence. Following a slightly modified procedure of the Kiliani–Fischer cyanohydrin reaction reported by Kuhn and Baschang [32], aldoses were exposed to hydrocyanic acid in pyridine and triethylamine, replacing

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

• reaction is quite broad since it could be applied to secondary propargylic alcohols 72 (or an acetate derivative 73), to tertiary alcohols such as 74 or 75 and even to the O-trimethylsilyl cyanohydrin 76. The corresponding cycloisomerization products 77–81 were isolated in good to excellent yields (71–97

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

• iminosugars, L-1-deoxyaltronojirimycin (96), D-1-deoxyallonojirimycin (66), and D-1-deoxygalactonojirimycin (64), was reported by Overkleeft et al. to occur from a single chiral cyanohydrin 94, made available via a chemoenzymatic approach with almond hydroxynitrile lyase (paHNL) [68]. The key steps in the

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

• 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

• that Lewis base catalysis made a much greater contribution to the overall catalytic activity of VO(salen)NCS in propylene carbonate than in dichloromethane. Keywords: cyanohydrin; Hammett; kinetics; propylene carbonate; vanadium; Introduction The last 15 years have witnessed an explosion of activity

• in the area of asymmetric cyanohydrin synthesis [1], mostly using trimethylsilyl cyanide (TMSCN) as the cyanide source to produce enantiomerically enriched silyl-protected cyanohydrins, which can readily be converted into other, pharmaceutically important, bifunctional units, such as α-hydroxy acids

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

• were focused on screening the effect of diverse additives and also the applied voltages, in order to maximize the enantioselectivity and conversion of the reaction. While enantioselectivities for formation of cyanohydrin 3 were found to be comparable to analogous batch reactions, reactivity was

• ). Continuous-flow asymmetric cyclopropanation. Continuous asymmetric hydrogenation of dimethyl itaconate in scCO2. Continuous asymmetric transfer hydrogenation of acetophenone. Asymmetric epoxidation using a continuous flow membrane reactor. Enzymatic cyanohydrin formation in a microreactor. Resolution of (R/S

Diastereoselective and enantioselective reduction of tetralin- 1,4-dione

• E. Peter Kündig and
• Alvaro Enriquez-Garcia

Beilstein J. Org. Chem. 2008, 4, No. 37, doi:10.3762/bjoc.4.37

• -trimethylsiloxy-4-oxotetralin-1-carbonitrile (10) as protected equivalent of dione 2. Slow addition over 2 h of a THF solution of ketone 10 to a solution of BH3·THF (0.6 equiv) and catalyst 8 in THF at −30 °C gave, after MeOH quenching and TBAF deprotection, (−)-9 in 85% yield and 95% ee (Scheme 6). Cyanohydrin

• silylether 10 partially hydrolyzes on silica and, as it turned out, isolation of this intermediate is not required and this provided a reliable and efficient sequence to highly enantiomerically enriched 9 (Scheme 5). In the course of this optimization, we also isolated cyanohydrin 11. We note literature