Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• the presence of acetic anhydride [46]. As the peroxy compounds can react with alkenes, leading to the anti-products via epoxy intermediates, substrates must be added slowly by a syringe pump to provide reasonable yields and diastereoselectivity. The diastereoselectivity of the reaction can be

• diastereoselective catalytic fluorination was developed by the same group (Scheme 14, bottom) [65] using the lactate-based resorcinol derivative 44 as the catalyst. By this route chiral 4-fluoroisochromanones 46 could be accomplished in high enantio- and diastereoselectivity. The same I(III) intermediate 47 was

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• 98% to afford α-benzoyloxy propargylic derivatives 39. Again the strategy can be applied to the late-stage modification of steroids with high levels of diastereoselectivity. λ3-Iodane reagents: azidobenziodoxolone (ABX) and chlorobenziodoxolone In a similar manner to the previously described

• the limiting components, with nearly quantitative yields and complete diastereoselectivity [102][103][104][105]. Such a highly efficient atom-transfer process has provided the opportunity to design a tandem of C–N and C–C bond-forming reactions that relies on an initial step of catalytic nitrene

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• % yield with a diastereoselectivity ratio of 92:8 (Table 1, entry 13). Additionally, preformed CoBr2(L3) gave a similar result (Table 1, entry 14). During the transformation, the chromium catalyst ligands inhibited the reaction (Table 1, entries 15–17). Also, the reaction was highly dependent on the

• good yields (Scheme 8). During the investigation of allenes, it was observed that, when oxygen substituents were present at the allenyl position, coupling products with reversed diastereoselectivity were obtained (Scheme 9). Thus, treatment of 4-benzyloxybuta-1,2-diene (5) with 1 and 3a under identical

• reaction conditions mainly afforded the anti-configured homoallylic alcohols 7–10 in 46–65% yield. A similar reversed diastereoselectivity was observed in the coupling reaction of silyloxy allene 6, leading to 11 in 46% yield (anti/syn = 73:27). A stoichiometric reaction using phenylchromium(II or III

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• -substituted benzaldehydes gave the best enantioselectivity, and the desired aldol products were obtained with anti diastereoselectivity (Scheme 26). In addition, when DMF was used as solvent, a positive effect on the enantioselectivity but negative effect on the diastereoselectivity were observed. The

• aldol reaction between 21 and 70 and offered superior diastereo- and enantioselectivities in the presence of chloroacetic acid (96% conversion, 86:14 anti diastereoselectivity and 73% ee) (Scheme 25). Under the optimum reaction media, a series of diverse benzaldehydes bearing electron withdrawing groups

• activity and stereoselectivity of catalyst 99. As shown in Figure 11, this catalytic system renders to use the calixarene cavity and in consequence of this both the high diastereoselectivity and enantioselectivity can be explained. Furthermore, when 99 used in 2 mol % can be recycled easily and re-used six

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• diastereoselectivity of 90% de was achieved in the reaction of 1-benzoylacetone (R2 = Me, R3 = Ph) which afforded the corresponding single diastereoisomeric product in 96% yield and 95% ee. In 2018, Tanyeli et al. reinvestigated this type of reactions in the presence of related cinchona alkaloid-derived squaramide

• (34–80% de). The lowest diastereoselectivity (34% de) was obtained in the reaction of a disubstituted substrate (R1 = 4,7-Cl2), showing that it was sensitive to the substitution of the aryl moiety of the isatin. In fact higher diastereoselectivities (≥60% de) were achieved for all other substrates

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• via participation of the amide carbonyl group (intermediate 74) dictated the formation of 1,2-difluorinated products 75 and catalyst 76 was identified as the optimal catalyst for this transformation. The 1,2-difluorinated products 75 can also be obtained with high diastereoselectivity by an anchimeric

Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• cation pool method as diaryldisulfides are the exclusive side products formed during carbocation generation. Thus, the reaction of acyliminium ion C1 with Me3Al afforded trans-1-(tert-butoxycarbonyl)-2-methyl-4-phenylpiperidine (2aa) in a good yield and virtually complete diastereoselectivity (cis/trans

• manner and good to high yields (Table 1, entries 4 and 5). Next, we examined the reaction of N-Boc-4-methyl-2,3,4,5-tetrahydropyridin-1-ium (C2) with nucleophiles (Table 2). Both, the reactivity and diastereoselectivity of the reactions were similar to those of C1 and the disubstituted piperidine

• ), because both ions led to similar stereoselectivities in the reactions with nucleophiles. As mentioned, the conformation of N-acyliminium cation C1–C4 was pseudo-equatorial and that of C5 and C6 was pseudo-equatorial (Figure 4). It is commonly assumed that the diastereoselectivity of the disubstituted

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• ) with 4 (R1 = Ph, R2 =H) afforded 20 in 51% yield. Since both meso-23 and rac-23 are well-described in the literature [33], we chose to study the diastereoselectivity of the reaction using the dimerization of enol ether 21. The geometry of the TMS enol ether 21 was established as being exclusively Z

• based on 2D-NOE NMR (Scheme 3). The enolate 21 was then converted into enolonium species 22 and cross-coupled with a second equivalent of 21 to give the two separable diastereoisomers of 23 one meso and one rac in 6:1 diastereoselectivity. This in conjunction with earlier work from our group [34

• good diastereoselectivity. We hope that the ease of carrying out and optimizing the procedure will make it useful for chemists interested in making unsymmetrical 1,4-diketones. Oxidative intermolecular cross-coupling of dissimilar enolates. Scope of the homo- and heterocoupling of enolates. The purple

Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions

• Kendra Leahy Denlinger,
• Lianna Ortiz-Trankina,
• Preston Carr,
• Kingsley Benson,
• Daniel C. Waddell and
• James Mack

Beilstein J. Org. Chem. 2018, 14, 688–696, doi:10.3762/bjoc.14.57

• used in liquid-assisted grinding (LAG) and properly chosen counter-ion pairing increases the percentage conversion of stilbenes in a mechanochemical Wittig reaction. Utilizing stepwise addition/evaporation of ethanol in liquid-assisted grinding also allows for the tuning of the diastereoselectivity in

• of the Wittig reaction under mechanochemical conditions [17][18]. The Wittig reaction is one of the most useful reactions for the synthesis of olefins [19][20][21][22][23]. Aside from its synthetic utility, its unique reaction mechanism (shown in Figure 1) and inherent diastereoselectivity has led to

• present, its dielectric constant will be the determining factor in diastereoselectivity, consistent with our previous observations. Counter-ion pairing We further hypothesized that, if the benzyl benzoate is formed through a six-membered ring intermediate to give (E)-stilbene as the major product, then

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• favour the major diastereoisomer (Table 1, entries 1–3). The use of a catalytic amount of base led to product 3a in a good yield (Table 1, entry 4) but with a loss of diastereoselectivity. Because the optically pure auxiliary and the conjugated ketone were not interacting well, a significant

• diastereoselectivity could not be obtained and we looked for improvements through the use of an appropriate chiral organocatalyst [63][64][65]. Indeed, within the same reaction conditions, the use of cinchoninium catalyst 18a afforded isoindolinone (S)-3a with higher de (54%), (Table 1, entry 5). We assumed such de

• with the chiral ammonium. Surprisingly, the diastereoselectivity initially obtained for 3a (Table 1, entry 5) was not improved by a decrease of the temperature to −10 °C (Table 1, entry 6) or by the use of polar solvents (Table 1, entries 7 and 8) or of another base (Table 1, entry 9). In order to

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• -position to the sulfur atom. Under the conditions, a camphor-substituted analogue was anodically fluorinated with moderate diastereoselectivity. Moreover, the anodic fluorination of a cyclic benzothioate such as benzothiophenone was also successfully demonstrated. In contrast, the anodic fluorination of S

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• high diastereoselectivity. In case of benzaldehydes with electron-withdrawing substituents in the para-position, syn-α-SF5-β-hydroxyalkanoic acid esters were produced. The reaction was also successful with meta-substituted benzaldehydes and o-fluorobenzaldehyde. In contrast, p-methyl-, p-methoxy-, and

• the other hand, meta-substituted benzaldehydes gave mainly the syn-aldolates 2j–l and small amounts of the anti-isomers 3j–l regardless of the electronic nature of the aryl substituent (Table 2, entries 10–12). 2-Fluorobenzaldehyde gave the highest yield (69%) and 83:17 diastereoselectivity (Table 2

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• based on the use of chiral substrates and enantioselective catalytic procedures. Keywords: asymmetric (aza)-Reformatsky reaction; asymmetric synthesis; chirality; diastereoselectivity; enantioselectivity; total synthesis; Introduction The Reformatsky reaction involves the formation of β

• followed by protection of the formed alcohols as silyl ethers by treatment with TPSCl (triphenylsilyl chloride), provided the corresponding chiral protected Reformatsky products 6 in 92% yield as a 77:23 mixture of (S,R)- and (S,S)-diastereomers (Scheme 3). In spite of its moderate diastereoselectivity (54

• -ribonolactone and chiral bromide 12 prepared from D-ribose [21]. On the basis of this double induction, the Reformatsky reaction performed at −78 °C in THF provided a complete diastereoselectivity, affording the corresponding chiral product 13 as a single diastereomer in 68% yield (Scheme 5). This process

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• (Scheme 4) [12]. Only diastereoisomer 6 was detected in the NMR analysis. Acid-promoted deprotection of hemiaminal 6 and subsequent oxidation of acetal 7 gave the enantiopure phthalide 1a in good yield. Although a high control of diastereoselectivity (using stoichiometric auxiliary strategy) was achieved

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• with Et3N·3HF proceeds with excellent diastereoselectivity [19]. Et3N·3HF is less acidic than Olah’s reagent, disfavouring SN1 and rearrangement pathways [20][21]. Indeed, the use of this reagent for the epoxide opening of cis-2 led to (±)-syn-3 in excellent yield (Scheme 2), with no significant

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• release of free (2S,3S)-CF3-threonine whose diastereoselectivity was determined to be about 96% by 19F NMR. Although in most of the reported cases, the free amino acid was released into the aqueous phase, and then purified by ion-exchange chromatography, we purified the free (2S,3S)-CF3-threonine by

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• compound, albeit in low yield and with poor regio- and diastereoselectivity (Scheme 19). Interestingly, the authors proposed a mechanism involving a chain propagation pathway, in contrast to the work of Jung and Han. A similar cascade reaction was also performed on diethyl 2-allyl-2-(3-methylbut-2-en-1-yl

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• -(arylsulfonylhydrazono)butanoates 74 as the CH-acids [27]. Diastereoselectivity of the reaction was found in the latter case (Scheme 47) [27]. The generation of two isomers of phosphorus ylides was carried out via the addition of triphenylphosphine to DAAD (dialkyl acetylenedicarboxylate), followed by protonation of the

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• [27]. Moreover, no evidence regarding either the diastereoselectivity and stereochemistry were reported. In 1998, Mazurkiewicz and co-workers developed a kinetic study of the base-catalyzed dimerization of azlactones. In this investigation, it was established that the dimerization reaction rates are

• concentration on the reaction outcome. Decreasing the amount of KTCA to 0.3 equiv, the diastereoselectivity slightly increased to 4:1 (Table 1, entry 9). Finally, NaTCA as salt gave 98% conversion and a good dr (6:1, Table 1, entry 13). Different basic conditions were evaluated without any improvements in terms

• presence of an electron-withdrawing aryl ring substituent R, the reaction worked well and afforded the product 2e in good yield and diastereoselectivity. When R1 was a benzyl group, the reaction tolerated the use of both electron-donating substituents and a non-substituted phenyl ring, affording the

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• oxazolidinone derivative 31 was first achieved with an excellent yield (88%) and diastereoselectivity (de > 95%). The chiral auxiliary was then removed and the free alcohol was oxidized to the corresponding aldehyde 32. Alkene 33 was then obtained after olefination of 32 with low selectivity ((Z):(E) = 64:36

• O-deprotection, N-Fmoc-protection and oxidation to the carboxylic acid afforded the final Fmoc-Ala-ψ[(Z)-CF=CH]-Gly (49). Then, it was discovered that the diastereoselectivity of the addition of the Grignard reagent on 47 was enhanced when dimethylzinc (Me2Zn) was used as an additive (Table 1) [39

• trialkylaluminium reagents and CuLi (Scheme 14A) [44][45]. Even if the diastereoselectivity of the reaction was excellent, two problems remained. First, an excess of trialkylaluminium reagent and of copper had to be used. Second, trialkylaluminium reagents are not widely available. As an alternative, they proposed

An efficient synthesis of 1,6-anhydro-N-acetylmuramic acid from N-acetylglucosamine

• Matthew B. Calvert,
• Christoph Mayer and
• Alexander Titz

Beilstein J. Org. Chem. 2017, 13, 2631–2636, doi:10.3762/bjoc.13.261

• desired alkylation step provides 13 in good yield and excellent diastereoselectivity using commercially available (S)-2-chloropropionic acid as the alkylating agent. Trityl deprotection could be readily accomplished without the need to protect the carboxylic acid, delivering the target compound 1 in good

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• the corresponding adducts in a stereoselective manner. Keywords: chiral oxazolidinones; diastereoselectivity; Mannich reactions; pseudo-C2 symmetry; trifluoromethyl; Introduction During these decades, we have been keenly interested in the 3-(trifluoromethyl)glutaric acid derivatives and developed a

• structural scope of imines 2 at the next stage (Table 2). As mentioned above, LDA and LiHMDS proved to work in a complementary manner in terms of their diastereoselectivity towards products 3. Therefore, we next tried to use both bases for the reaction with 1a and the resultant enolate was treated with a

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• low yields and diastereoselectivity. The reaction of sulfinylimine 3a with isopropylmagnesium bromide provided the sulfinamide 4a in only 13% yield with a ratio of diastereomers of 99:1. Only 10% of the addition product 4b were obtained by addition of methylmagnesium bromide to the N-sulfinylimine 4b

• ], others advised against its use as activation agent of aldimines, because side reactions were observed [13][54][55], which will also be further discussed below. We used THF or toluene as solvents and AlMe3 or Ti(OiPr)4 as activation agent. According to Ellman et al., the diastereoselectivity of the

• was reported to give very poor yields and low diastereoselectivity. In contrast to the argumentation of Xiao et al., who strongly recommended hard Lewis acids for the reaction of sulfinylimines with various ethynyllithium reagents [95], the crude imine 5k predominantly reacted with the Lewis acids Ti

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• tolerated. Alkylketone substrates were also successfully converted to 2-oxazolines. Installation of substituents on the tether led to facile formation of product 6m containing a quaternary carbon and compounds 6n and 6o but without any observed diastereoselectivity. Interestingly, the selectivity for 6o

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• investigation of different cyclic and acyclic sulfoxides 29, they could show that the diastereoselectivity of this reaction can be clearly improved by using the chiral cinchona alkaloid-based ammonium salt A8 compared to the use of achiral tetraalkylammonium salt-based PTCs [127][128][129]. In 2013, Maruoka’s