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

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• sequence to 21, the revised approach provided a similar overall yield and proved superior in terms of diastereoselectivity. As for the synthesis of 23 in the 1st generation approach, alkyl iodide 31 was also prepared from aldehyde 22. While the sequence leading to 31 was clearly longer than for 23 (10

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• modest diastereoselectivities (65:35) in favor of the 5’R-isomer, whereas O-silyl groups promoted higher diastereoselectivities (up to 99:1) in favor of the 5’S-isomer. A study related to this protecting group effect on the diastereoselectivity is reported. Keywords: diastereoselective alkynylation

• ][17][35][42][43][44][45][46][47]. Aside from the use of chiral ligands promoting an excellent facial discrimination of the aldehyde [34], the addition of Grignard reagents usually proceed with moderate diastereoselectivity and yield (Table 1) [12][35][43][44][45][46][48]. In the course of our program

• 5a [51], R1 = TIPS). Some compounds were also N3-allylated (1b, 4b and 5b) to evaluate the possible influence of R2 on the diastereoselectivity of the nucleophilic addition (Scheme 1). Primary alcohols 1–5 were submitted to an oxidation/Grignard addition sequence leading to the corresponding

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• natural fusaricidin by the Jolliffe group employed a ring closure via a lactonization in solution and subsequent attachment of the side chain to the cyclized depsipeptide [10]. Since the macrolactonization approach suffered from diastereoselectivity issues and low yield, it was decided to perform an on

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• HPA and an imine component which has been postulated but never obtained in similar reactions. Keywords: Castagnoli–Cushman reaction; diastereoselectivity; homophthalic anhydride; indolenines; lactam synthesis; multicomponent reactions; Introduction The reaction of imines (prepared in a separate step

• -diastereoselectivity of the CCR is well documented in the literature [33] and is, therefore, unsurprising. However, the stereocontrol achieved in this reaction over 3 stereocenters present in 10l (obtained in 81% yield as a single diastereomer) is certainly quite noteworthy and was confirmed by X-ray analysis (Figure

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• asymmetric catalytic synthesis of saturated spirocyclopentaneoxindoles containing four consecutive stereocenters with 3-substituted oxindoles and nitrovinylacetamide using a bifunctional thiourea catalyst in good yields (up to 95%) with excellent diastereoselectivity (up to 3:97) and enantioselectivity (up

• , respectively (Table 1, entries 1 and 2). Further experiments showed that a bifunctional thiourea catalyst d was the most efficient for the synthesis of spirocyclic oxindole derivatives in good yields (80%) with excellent diastereoselectivity (8:92 dr), and moderate enantioselectivity (83% ee, Table 1, entries

• oxindoles in this transformation with nitroolefins (Scheme 2). In general, the diverse 3-substituted oxindoles 1a–j with electron-donating, electron-withdrawing, or halide groups could undergo a smooth reaction with nitrovinylacetamide (2a) in moderate yields, good diastereoselectivity, and general

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• THF hence forming an oxocarbenium ion. The latter is subsequent attacked by the nucleophilic alcohol to provide the 1,2-trans glycoside with good diastereoselectivity and moderate yield. This methodology holds tremendous potential if the alcohol acceptor is a saccharide moiety as the

• diastereoselectivity of the reaction is good, the mechanism unique, and the synthesis of the donor is reasonably easy and inexpensive. However, to date no follow-up study has been published. 3.3 Lewis acid-mediated activation Lewis acid-mediated methods for anomeric activation of protected donors in glycosylation are

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• borohydride delivered the desired alcohol in a 10:1 diastereoselectivity. The alcohol was methylated by a protocol involving methyl iodide and LiHMDS, that had been previously used by the group [45]. The stannane was finally converted to the iodide 55 by iododestannylation [95] to complete the fragment

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• as solvent. Under these conditions the yield of the Michael adducts was 95–99% within 7 hours. The diastereoselectivity was moderate (dr = 70:30–78:22) in favour of the syn-diastereoisomer and enantioselectivites were ee ≈ 68% for the syn-adducts and ee = 44–63% for the anti-adducts. The

• studied using OC4 as the organocatalyst (Table 2). The best results were obtained with methylcyclohexane as the solvent at 0 °C reaction temperature. Under these conditions after 24 h the reaction yield was high (87%), the observed diastereoselectivity was 92:8 in favour of the syn-adduct and the

• is worth mentioning that on reducing the catalyst loading to 5 mol % the reactivity remained good and the diastereoselectivity and enantioselectivity were only slightly affected. It has been reported that additives present in the reaction medium can lead to improved results without changing other

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• quaternary center with high diastereoselectivity as a consequence of the Stetter–Aldol–Aldol (SAA) reaction sequence. The Stetter–Aldol–Aldol conversion of the phthaldialdehyde derivatives 75 and o-formyl substituted chalcones 76 using the thiazole based carbene 78 as a precatalyst allowed to obtain spiro

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

• approaching an sp2-hybridized C1 in the TS [41]. Effect of silyl protective groups on the selectivity The bulkiness of TBS groups in donors such as 20 can have a significant influence on the diastereoselectivity. Thus glycosylations with 20 (Table 1) gave exclusively the β-glucoside presumably due to steric

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• diastereoselectivity ranging from 5 to 65% de. Electrolyses without a coacid led to diastereomeric homo-coupling products in 21–50% yield with ratios of diastereomers being 1.17:2.00:0.81 to 7.03:2.00. The stereochemistry of the new stereogenic centers was confirmed by X-ray structure analysis and 13C NMR data

• . Keywords: anodic decarboxylation; diastereoselectivity; Kolbe electrolysis; radical hetero-coupling; radical homo-coupling; Introduction Intermolecular radical additions with high diastereoselectivity have been described for a number of cases [1][2][3][4][5][6][7][8][9]. There are much fewer reports on

• intermolecular diastereoselective radical coupling reactions [10][11][12][13][14][15][16]. There are some examples of high diastereoselectivity in the coupling of radicals generated from azo compounds [10][11], in intramolecular coupling of radicals, that are obtained by photochemical activation [12][13][14

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• were obtained in high Z-diastereoselectivities (de = 74–88%), whereas the phosphonate 4f was provided with an excellent Z-diastereoselectivity (de = 100%) when R1 = Ph. In this work, the observed high Z-diastereoselectities are in good agreement with a previous report by Basavaiah and co-workers on the