A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• electrochemical synthesis of axially chiral biaryls. Reaction conditions: undivided cell, 2 (0.3 mmol), H2O (1 mL), MeCN (9 mL), 3.5 F mol−1. aIsolated yield of the major diastereomer. bDetermined by 1H NMR analysis of crude reaction mixture. cCombined yield of the two diastereomers. Proposed reaction mechanism

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• ) Photocatalytic oxyamination, b) photocatalytic diamination, and c) proposed mechanism for photocatalytic oxyamination using copper(II) as a terminal oxidant. Scope studies for dual-catalytic alkene difunctionalization using 2.5 mol % 3, 30 mol % Cu(TFA)2, and a 15 W blue flood lamp. Diastereomer ratios >20:1

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

• phosphinite 6a which afforded a 73:27 mixture of the diastereomeric phosphine oxides 7a/7’a (86%). The major diastereomer 7a corresponds to a sigmatropic rearrangement occurring on the most hindered face (cis to the aromatic group) of the cyclopropene which was somewhat surprising. Substitution at the para

• -position of the aromatic group at C3 significantly affected the diasteomeric ratio with an increase observed with the mesomeric donor methoxy group in favor of diastereomer 7b (7b/7’b = 78:22) compared to 7a/7’a, and a drop of diastereoselectivity when a fluorine atom (7c/7’c = 60:40) or a hydrogen atom

• (7d/7’d = 52:48) were present. An inversion of the face selectivity was detected in favor of diastereomer 7’e (7e/7’e = 43:57) arising from the rearrangement of phosphinite 6e possessing a p-trifluoromethylphenyl substituent. Replacement of the acetal protecting group of the hydroxymethyl substituent

Systematic synthetic study of four diastereomerically distinct limonene-1,2-diols and their corresponding cyclic carbonates

• Hiroshi Morikawa,
• Jun-ichi Yamaguchi,
• Shun-ichi Sugimura,
• Masato Minamoto,
• Yuuta Gorou,
• Hisatoyo Morinaga and
• Suguru Motokucho

Beilstein J. Org. Chem. 2019, 15, 130–136, doi:10.3762/bjoc.15.13

• their characteristic signals. Keywords: cyclic carbonate; diastereomer; diol; limonene; NMR; Introduction (R)-Limonene (LM) is a naturally occurring terpene, and therefore a very attractive and renewable resource [1]. Its derivatives have versatilely and widely been studied [1][2][3][4]. Otherwise

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• the syn diastereomer 18 in high stereoselectivity (93:7). After silylation of the free hydroxy group, the cleavage of the PMB ether with DDQ led to alcohol 20 in 77% yield for the two steps. Ring-closing metathesis of diene 21, obtained by O-vinylation of 20, gave the dihydropyran 22 in 53% overall

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• . Gratifyingly, treatment of 4 with TiCl4 in the presence of commercially available 1-methyl-1-(trimethylsilyl)allene at −78 °C for 1 h afforded the desired cis-6,5-bicylic core 5 in 63% yield as a single diastereomer. The desilylated product 6 was also obtained as a mixture of diastereomers. The high

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

• conversion to the diastereomer by oxidation and reduction. Conformational analysis of some of the resulting diols obtained under McMurry conditions was complicated by the presence of several conformers of similar energy. The pinacol coupling appears to start at the ketone, as indicated by the selective

• , those conformations are within 10 kJ/mol range of each other. However, only one of those conformations shows the required short distance between 14-H and 3-CH3, making the configuration (2R,3S,14R) probable for diastereomer 18. In the preferred conformation of 18, all non-sp3-hybridized carbon atoms of

• the ring system and the adjacent atoms are located almost in plane, whereas the isopropyl group and ring carbons C3 and C4 are located on opposite sides of that plane. Since the oxidation/reduction sequence has affected the configuration at C2, diastereomer 19 is assigned the configuration (2S,3S,14R

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• at the betaine intermediate prior to epoxide formation through displacement of THT. This is supported by example 9 which contained a para-methoxy group at the aldehyde component but was isolated as a single diastereomer [28]. Functional groups that are not compatible with this method include phenols

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• activation of F2 give intermediate F3. Finally, protonolysis provides the desired product 45 and an active Co(III)Cp*. Due to the low activation energy, the thermodynamically less stable Z diastereomer is preferred in the reaction, which is in contrast to the rhodium(III)-catalyzed reaction [82]. Later, Li

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• first comprised of a single diastereomer as a salt 8, while a second fraction was obtained as a diastereomeric mixture (8:9, 3:1), again as salts (Scheme 1). Mass spectrometric data observed for 7 supported the formation of a diaminated pyrrole product, with a protonated molecular ion of m/z 373.3556 [M

Bi-mediated allylation of aldehydes in [bmim][Br]: a mechanistic investigation

• Mrunesh Koli,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2018, 14, 2198–2203, doi:10.3762/bjoc.14.193

• alcohol 2l' was obtained as the major diastereomer (Table 2, entry 11), although the reaction diastereoselectivity was inferior to that by the Luche’s protocol using Zn metal [42]. In all the reactions, the products were easily isolated by extracting the reaction mixture three times with Et2O followed by

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

• , and a coupling value of 3J = ca. 8.0 Hz indicated the anti-form (Table 1, entry 1) [17]. The addition of PPh3 (20 mol %) resulted in an increase in the product yield to 45% with a similarly diastereomer ratio (Table 1, entry 2). The use of the chromium catalyst, Mn reductant, and TMSCl was crucial for

• and electron-deficient aryl aldehydes, as well as 2-furylaldehyde, were well tolerated in the reaction, leading to the formation of the corresponding homoallylic alcohols with similar diastereomer ratios (4a–f). Additionally, alkyl aldehydes were also successfully used in the coupling reaction, albeit

• (this work). Screening of aldehydes in the Co/Cr-catalyzed three-component coupling reaction. All yields are determined after isolation. The values in brackets indicate the diastereomer ratio of the syn and anti products, determined from 1H NMR spectra. Screening of aryl iodides in the Co/Cr-catalyzed

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

• major diastereomer with moderate yield but the selectivities were low. Acetone (94) was also used as substrate but only 40% ee was obtained although the yield was 80% (Scheme 26). In order to create a more compact transition state and increase the selectivity by this way in direct stereoselective aldol

• derivatives using R-(−)-2-methylbutanol as hydride source [71]. As shown in Scheme 34, independent of which calix[4]arene diastereomer (111 or 112) was employed, when ortho-fluorobenzophenone was used as substrate, the enantioselectivity remained at 20%. But the MPV enantioselectivity was found sensitive to

London dispersion as important factor for the stabilization of (Z)-azobenzenes in the presence of hydrogen bonding

• Andreas H. Heindl,
• Raffael C. Wende and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 1238–1243, doi:10.3762/bjoc.14.106

• kcal mol−1 for 5–7, respectively, relative to the lowest energy conformer) were then re-optimized at the B3LYP/6-31G** [26][27][28][29] level of theory with and without D3(BJ) [30][31] dispersion correction (gas phase) (conformations of one enantiomer of each diastereomer of 4 were analyzed. The

• maximum stabilization was found for (R,S)-4. For the other diastereomer, see Supporting Information File 1). As it can be seen in Table 2, the computations reproduced the stabilization of the tight conformations relative to their open forms, which is in agreement with the experimentally observed kinetics

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• glycosylative protocol. Assuming equal preference of formation for each and every possible diastereomer across the three glycosylation steps a mixture of 8 different diastereomers may be formed if the four monomers are sequentially added in a (1 + 1 + 1 + 1) one-pot strategy. However, the number of

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• purity of the major diastereomer (er 99:1). With the help of quantum-chemical calculations, we have proposed a transition state model for the Michael addition. Structures of pregabalin and methylpregabalin. Transition state models for the reaction of (R)-6 with dimethyl malonate using catalyst C7 (M06-2X

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

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

• % de), the utility of this procedure was demonstrated by converting the minor (S,S)-diastereomer 6 into the orthogonally protected γ-hydroxylysine derivative 7 which is found in the potent antitumor agent glidobactin A [19]. Another chiral electrophile, such as aldehyde 8 prepared in five steps from

• (−)-citronellal, was submitted by Luesch and Zhang to diastereoselective zinc-mediated Reformatsky reaction with tert-butyl bromoacetate (9a) in THF at reflux [20]. The process afforded in almost quantitative yield (97%) the corresponding β-hydroxy ester 10 as a single diastereomer, as illustrated in Scheme 4

• -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

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• –Wadsworth–Emmons reaction with triethyl 2-phosphonopropionate (19) yielded ethyl (E)-2,4-dimethylhex-2-enoate (20) as a separable mixture of E and Z stereoisomers (E/Z = 10:1). The purified E diastereomer was reduced with DIBAl-H to the corresponding alcohol 21. A PCC oxidation and addition of

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

• substituents is of interest. Here we describe optimisation efforts in the synthesis of anti-2,3-difluorobutane-1,4-diol, as well as the synthesis of the corresponding syn-diastereomer. Both targets were synthesised using an epoxide opening strategy. Keywords: acetal isomerization; deoxyfluorination; epoxide

• this contribution, we report on work directed at the further optimisation of the synthesis of anti-5, as well as on a gram-scale synthesis of its diastereomer (±)-syn-5, a novel compound. Results and Discussion Optimisation of the synthesis of anti-5 While the synthesis of anti-5 as described in Scheme

• a very small extent. Separation of the diastereomers proved not possible. Finally, deprotection of (±)-syn-4 by palladium catalysed hydrogenolysis led to (±)-syn-5. Recrystallization to remove the minor diastereomer was not successful. Conclusion A gram-scale synthesis of both syn- and anti-2,3

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• -phenyl-1,3-butanedione resulted in the formation of two diastereomers 7a and 7b in a ratio of 6:5 which in DMSO solution exist in diketonic form (Table 1, entry 2). This was confirmed by spectral data: two pairs of dublets (5.04 and 5.59 ppm, J = 2.6 Hz, for the major diastereomer and 5.34 and 5.52 ppm

• , J = 2.9 Hz, for the minor diastereomer) indicate the coupling of H7 and H1’ in both isomers and the absence of the enolic forms (Table 2). However, we were unable to attribute each set of signal to specific diastereomer 7a or 7b because the coupling constant values for H7 and H1’ were very close

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

• separated at this stage by column chromatography. The major diastereomer 7a was used in the following steps. Hydrolysis of the oxazolidine, followed by Jones oxidation of the alcohol 8, allowed us to recover the desired acid 9 in good yield (90%). The optical rotation of a solution of the product 9 (2S,3R

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

• diastereomer was assigned by X-ray analysis. Finally, one of the products was selectively reduced to provide a functionalized analogue of streptopyrrolidine, a marine natural product isolated from Streptomyces sp. As shown in Table 1, our studies started with the synthesis of dimer 2a using azlactone 1a in the

• major diastereomer was isolated after purification through column chromatography or simple recrystallization in good to excellent yields. The relative configuration to C11 and C9 of the major diastereomer was assigned by X-ray crystallographic analysis of compound 2a (Figure 2) [28]. The other products

• (Scheme 3). Compound 2c was dissolved in a mixture of acetic acid and NaBH4, cooled to 0 °C to afford the highly functionalized (+/−)-streptopyrrolidine analogue 6 in 70% yield as a unique diastereomer. Streptopyrrolidine was isolated from the marine bacterium Streptomyces sp. and has exhibited a

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

• File 1 for further details). Interestingly, when the alkylation of 12 was carried out using racemic 2-chloropropionic acid, a 3.3:1 mixture of diastereomers 13 and 14 was obtained, favouring the desired diastereomer 13 (Scheme 3). The diastereomers were separable by HPLC following trityl deprotection

• to 90 °C, 30 min; (d) trifluoroacetic acid, CHCl3, 0 °C to rt, 3 h. Synthesis of AnhydroMurNAc and diastereomer 5. Conditions: (a) (±)-2-chloropropionic acid, NaH, dioxane, 45 °C to 90 °C, 3 h; (b) trifluoroacetic acid, CHCl3, 0 °C to rt, 3 h. Supporting Information Supporting Information File 434

Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• change in selectivity was observed while using electron-withdrawing methyl amide 9d; the influence of the para-nitro substituent decreases the yield of the desired cis-diastereomer to only 12%. Utilization of non-aromatic methyl amides 9e and 9f, synthesized from L-norvaline and L-methionine methyl

• transformation (shown in Scheme 1b) delivered relatively high selectivity with imidazolidinones derived from L-phenylalanine this amino acid derivative was used as coupling partner. 1-Pyrene carbaldehyde 10b gave only a minor excess of the cis-diastereomer (S,S)-3b. For mesityl carbaldehyde 10c the desired

• isomer was obtained in 52% yield whereas the more sterically demanding aldehyde 10d led to a switch in the selectivity, giving the desired (S,S)-diastereomer in only 23% yield (Table 2). Conclusion We were able to synthesize 10 different imidazolidone-based organocatalysts with yields of the desired 1,3

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

• 15 and 16). As described above, facile isolation of 3 was sometimes hampered by contamination of the substrate 1a and/or 4-toluenesulfonamide 5 which is noticed by the absence of isolated yields shown in brackets in Table 2. The configuration of the major diastereomer of 3a (Table 2, entry 1) was

• . Crystallographic analysis of the major diastereomer of 3a (some hydrogen atoms are omitted for clarity). Each color represents the following atoms: gray, carbon; white, hydrogen; blue, nitrogen; red, oxygen; green, fluorine; yellow, sulfur. Explanation of the construction of the main stereoisomers. Optimization of