A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• asymmetric hydrogenation of ketones [22]. They showed that upon reduction with Raney nickel powder electrodes modified with (R,R)-(+)-tartaric acid, 2-hexanone 3 was converted to (S)-(+)-2-hexanol 4 with an average optical purity of 4%, whereas Raney nickel powder electrodes modified with (S,S)-(−)-tartaric

• catalyze the enantioselective hydrogenation of prochiral ketones 18. The prochiral ketones such as acetophenone, 1-tetralone and 1-indanone were reduced to their corresponding alcohols 20a, 20b and 20c, respectively, with moderate optical yields, with formation of (S) as major enantiomer (Scheme 5). After

• electrocatalytic hydrogenation of α-keto esters 12 to afford corresponding hydroxy esters 13b and 13c with appreciable enantioselectivities (Scheme 6). Following the pioneering works by Grimshaw et al. [28] in 1973, Gileadi and co-workers showed that the addition of quinidine or related alkaloids to the reaction

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• -acetylation using NaOMe in MeOH followed by hydrogenolysis in a ThalesNano continuous flow hydrogenation assembly using a 10% Pd-C cartridge [29]. After three cycles of hydrogenation, formation of the target pentasaccharide 1 was evident from the mass spectrum (Scheme 4). Conclusion In conclusion, the

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• has occasionally led to a mixture of isomers or even the Z-isomer as the predominant one [22]. Hydrogenation of 10a led to saturation of the double bond as well as concomitant removal of the O-benzyl group leading to SAHA (1) in an acceptable overall yield of 61% over three steps. On the other hand

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• ligands that were obtained from readily available natural (1S)-β-pinene and (1S)-α-pinene [18]. We applied these ligands for the formation of the ruthenium complexes, which were successfully used as catalysts in asymmetric transfer hydrogenation of prochiral ketones. In continuation of our studies on the

• -workers synthesized diphosphines with a pinane framework [19]. Results and Discussion Synthesis of allylic alcohols In the first step, commercially available natural (1R)-α-pinene (1) was oxidized with lead(IV) acetate to produce (+)-verbenone (2) in 58% yield (Scheme 1) [20]. Hydrogenation of 2 with

Photochromic diarylethene ligands featuring 2-(imidazol-2-yl)pyridine coordination site and their iron(II) complexes

• Andrey G. Lvov,
• Max Mörtel,
• Anton V. Yadykov,
• Frank W. Heinemann,
• Valerii Z. Shirinian and
• Marat M. Khusniyarov

Beilstein J. Org. Chem. 2019, 15, 2428–2437, doi:10.3762/bjoc.15.235

• cyclohexenone (6 and 7) bridges via intermediate bromoketone 2 and chalkone 5. Cyclopentenone 3 was synthesized by adapting a previously reported two-step protocol [35] starting from ethyl 4-(2,5-dimethylthiophen-3-yl)-3-oxobutanoate and bromoketone 2. Ionic hydrogenation [36] of 3 provided diarylethene 4 with

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• converted to C-3-tetrasubstituted furanoid sugar azido ester 3 as per our reported protocol [12]. Hydrolysis of the ester functionality in 3 with LiOH at room temperature afforded azido acid 4a in 92% yield, while hydrogenation of 3 using 10% Pd/C in MeOH at room temperature for 3 h afforded the amino ester

• 4b in 86% yield (Scheme 1). The coupling of 4a and 4b using 2-chloro-1-N-methylpyridinium iodide (CMPI), as a coupling reagent, in the presence of Et3N in dichloromethane at 40 °C for 12 h gave azido ester dipeptide 5 in 75% yield. Hydrogenation of 5 using 10% Pd/C in methanol gave amino ester

• converted to amino acid di- and tetrapeptides 8 and 9, respectively, using hydrolysis followed by a hydrogenation reaction protocol (Scheme 2). In order to get cyclic peptides I and II (Figure 1), an individual intramolecular coupling reaction of linear dipeptide 8 and tetrapeptide 9 was attempted. Thus

Attempted synthesis of a meta-metalated calix[4]arene

• Christopher D. Jurisch and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195

• products that then complicated the purification without increasing the yield. In our hands, this new method was found to be reproducible (gram scale) and was thus used to generate mononitrocalix[4]arene 9 for use in subsequent steps. Reduction of mononitrocalix[4]arene 9 under transfer hydrogenation

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• mixture of 51 and 52, subsequent Pd/C-catalyzed hydrogenation and tetrabutylammonium fluoride (TBAF)-mediated desilylation yielding the desired tricyclic 54 (83% yield, 98% ee). Overall, the known intermediate 7-oxotriptophenlide 59 was obtained in an efficient, elegant and scalable way in 10 steps with

• formal synthesis of triptolide and triptonide (Figure 2, route M) [48]. This synthesis highlights the use of Noyori’s ruthenium-catalyzed enantioselective transfer hydrogenation to introduce the chiral center; the indium(III)-catalyzed cationic polyene cyclization to construct the tricyclic A-, B- and C

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• diastereoselectivity (syn:anti >99:1) during the reduction. To unambiguously determine the diastereomeric ratio, the anti-1,3-diol corresponding to 10 was prepared from 7 by RuCl3–PPh3-catalyzed hydrogenation [63][64]. However, the two diastereomers had identical proton NMR spectra. The terminal hydroxy group of 10

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• catalytic hydrogenation but metal-ammonia reduction (Birch reaction) and organic acid in anisole (vide infra) can be efficiently applied. We begin with a short presentation of syntheses of aziridine-2-carboxylates, the corresponding aldehydes and 2-methanols. Review Syntheses of starting materials Synthesis

• nucleophiles to provide 9 or even by catalytic hydrogenation to form 10. Thus, biologically important fragments like vicinal amino alcohols 11 or 2-amino-1,3-propanediols 12a [Nu = OH] can be obtained in highly enantioselective procedures preserving the absolute configuration at C2. The latter compounds are

• NaBH4/ZnCl2 mixture (chelation controlled) gave the aziridine alcohol 20 as a major product. Reductive opening of the aziridine ring produced the amino alcohol 21 which was transformed into the substituted oxazolidin-2-one 22. Its catalytic hydrogenation effected deoxygenation at the benzylic position

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• , recyclable catalyst in the N-arylation of indoles [45][46]. Copper catalysts have shown exceptional enantioselectivity for reactions such as hydrosilylation, hydroboration, and heterogeneous as well as homogeneous hydrogenation [47][48][49]. Also, the copper salts found used as oxidants in a number of

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• enantioselectivity are also known [13][14][15][16][17][18]. The studied methods for obtaining acyclic sulfones with stereogenic centers in the side chain are more limited. One of the most significant approaches to obtaining both cyclic and acyclic chiral sulfones is asymmetric hydrogenation in the presence of

• transition metal complexes. The preparation of hydroxy sulfones from β-ketosulfones in the presence of Ru [19][20], Ir [21] and Rh [22] complexes was described. Chiral sulfones were also obtained by hydrogenation of the C=C bond with α,β-unsaturated sulfones in the presence of Ir(I) complexes with P,N

Mechanochemical amorphization of chitin: impact of apparatus material on performance and contamination

• Thomas Di Nardo and
• Audrey Moores

Beilstein J. Org. Chem. 2019, 15, 1217–1225, doi:10.3762/bjoc.15.119

• stainless steel ones, since the latter caused the reactive mixture to adhere to the jars, which was not the case of the former. In another example, for the metal-free transfer hydrogenation of carbonyl compounds, PTFE was used instead of steel to eliminate the possibility of catalysis from the milling media

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• yields varying from poor to good (10–87% yields, Scheme 2). The transfer hydrogenation was selected as common hydrogenation using conditions with hydrogen gas and palladium on carbon lead to very low yields or no recovered product during the synthesis of 1a,b. Unfortunately, no arenes bearing halogen

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• appended. Unfortunately, reactions of 6 and 8 utilizing catalytic hydrogenation, lithium aluminium hydride by itself as well as with added aluminium chloride or samarium iodide produced only trace amounts of an amine (e.g., 9). When samarium iodide was used as the reagent, the only discernible product (not

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• [11][12][13][14] of compound 7 or its relay surrogate 8 might give rise to the conjugated triene 6, chemoselective hydrogenation [15] of which would generate the target molecule 1. Similar to the disconnection of trienyne 3, the metathesis substrates 7 and 8 can be derived from aldehyde 9, which is

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• = R2 = H, instead of β-glycosyl, respectively). Results and Discussion Most syntheses of dihydrostilbenes rely on a carbonyl olefination followed by hydrogenation of the stilbene [7][8][9]. However, this route appeared not attractive, particularly as our attempts to hydrogenate highly substituted

• , partial hydrogenation of the aromatic rings had to be suppressed. Nevertheless, the aglycon 9 of scorzodihydrostilbenes B and D (2 and 4) was obtained in good yield from 8a. Hydrogenolysis of ketone 8b led to hydroquinone 10, however, along with a minor amount of mono-deprotected phenol 11. The main

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• shows the synthesis of the mannosamine derivatives Ac4ManNCp(H2) and Ac4ManNCyc(H2) (H2 indicates the cyclopropane moiety, i.e., the formal hydrogenation of the corresponding cyclopropene) as well as their transformation into the DMB-labeled sialic acids that served as reference compounds for the DMB

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• formation of the gem-dichloro-α-lactam intermediate 17f which would undergo ring opening by nucleophilic addition of pyrrolidine followed by hydrolysis of the resulting α,α-dichloro-α-aminoacetamide 18f (Scheme 12). To access aminocyclopropanes, the hydrogenation of (arylmethylene)cyclopropane 13f was

• intermediates K which would then react with trifluoroacetic anhydride to produce N,O-bis(trifluoroacetyl)carbamates L. Trifluoroacetamides 51–54 would be generated from adducts L after hydrolysis of the reaction mixture (Scheme 19) [53]. To control the diastereoselectivity of the hydrogenation of alkylidene[(N

• -acylamino)cyclopropanes] possessing a single substituent at C2, it is possible to rely either on the steric hindrance or on the coordinating ability of the amide group. Thus, the hydrogenation of trifluoroacetamide 51 catalyzed by Pd/C afforded N-trifluoroacetylaminocyclopropane 55 as the major diastereomer

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• mild conditions, hydrogenolysis of the benzyl ester group to the carboxylic acid and hydrogenation of the C=C double bonds at the silicon atoms (Scheme 7). The ability of the obtained derivatives, in particular the carboxylic acids, to generate nanostructured materials through self-organization

• of OVS via CM with styrenes. Cross metathesis of OVS with carboranylstyrene. Synthesis of octakis[2-(p-carboxyphenyl)ethyl]silsesquioxane via CM and subsequent hydrogenation. Cross metathesis of monovinyl-POSS with olefins. Cross metathesis of monovinyl-POSS with highly π-conjugated substituted

• subsequent hydrogenation. ROMP of norbornenylethyl-POSS with 1,5-cyclooctadiene. Copolymerization of POSS-functionalized norbornene with DCPD. Copolymerization of tris(norbornenylethyl)-POSS with DCPD. Copolymerization of N-(propyl-POSS)-7-oxanorbornene-5,6-dicarboximide with 3-(trifluoromethyl)phenyl-7

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• hydrogenation of double bonds, especially for long reaction times. The ability of the Gr2 catalyst to form Ru–hydride complexes in the presence of alcohols is well-known and described in the literature [98][99]. Such complexes promoting C=C bond hydrogenation were detected in the PNB–PCOE(OH)–Gr2 system using

• NMR [97]. It is curious that the resulting multiblock copolymers reveal some crystallinity, whereas the parent PNB and PCOE(OH) are fully amorphous. It can be explained if we recall that hydrogenated PNB is a semicrystalline polymer [100]. The Pd/Al2O3 catalyst was used to promote the hydrogenation of

• nearly transparent and flexible upon hydrogenation [84]. Another approach to the post-functionalization of NB–COE multiblock copolymers was implemented in reference [101] via double-bond epoxidation in the presence of m-chloroperbenzoic acid (Scheme 10B). It was found that this reaction proceeds more

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• -benzyloxyacrylamide is reported. The reaction proceeds better in the presence of Grubbs’ second generation catalyst within short time and in good yields (57–85%) with a range of substrates. Subsequent hydrogenation of each of the CM products delivers the title compounds in moderate to very good yield (70–89%). An

• -isopropoxyphenylmethylene)ruthenium] (HG-II) was used under identical conditions. Hydrogenation of the later in the presence of Pd(OH)2/C proceeded uneventfully resulting in the saturation of the double bond as well as concommitant deprotection of the O-benzyl group. The one-pot CM-hydrogenation sequence using the same

• . Having established the conditions for stepwise CM and hydrogenation reactions, we extended the study to other substrates (Table 1). For example, the yields of the two steps for dodecene forming 6b and 7b were more or less similar with those for decene when either of the 2nd-generation catalysts was used

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• constant of approximately Kd ≈ 10−15 M [28]. Initially, an achiral Wilkinson-type catalyst was attached to perform hydrogenation [27]. Nowadays, a broad variety of artificial metalloproteins based on this technology has been established [20][29]. Dative anchoring offers the possibility to liberate the

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• hydrogenation was preferably used although, when incompatible with the substrates, sodium borohydride was employed. In most cases, large proportion of the expected substituted malonates 3a–al were observed by 1H NMR. Thus, in order to simplify even further this procedure, these crude malonates were subjected to

• 2ae. First of all, reduction of the alkylidenemalonate 6ae using a palladium-based catalytic hydrogenation also led to the concomitant hydrogenation of the furan ring to give compound 8. As depicted, this actually allowed us to prepare to the 2-tetrahydrofuranyl-bearing α-aminoester 10 in a 35

• % overall yield via α-hydroxyimino ester 9, but it also forced us to use borohydrides to avoid the furan ring hydrogenation. Accordingly, an extensive study of the reduction of compound 6ae with borohydrides was made. Trials included reactions run at 0 °C overnight, the use of wet ethanol or dry THF, the

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• acrylates 2n or 2o using sodium borohydride, the α-nitro esters 6n and 6o were isolated in the rather modest yields indicated in Table 1. We then focused on the model reduction of acrylate 2n into 6n. Since all our attempts to achieve a palladium-catalyzed hydrogenation failed, we tried other borohydride

• acid in ethanol overnight gave a sufficient amount of the (pure) target phenyl-bearing α-amino ester 10 which had been previously obtained by catalytic hydrogenation using palladium [20]. The same transformation sequences were used starting with compound 6n and provided the furan-bearing α-amino ester