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

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• selective and only one diastereomer was obtained, as supported by analytical data. X-ray analysis of the product confirmed the stereochemistry of the three chiral centres and the structure of 15a. To shed more light on the origin of the selectivity observed in the deprotection–cyclization transformation

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• was glycosylated in the presence of NIS/TfOH to afford tetrasaccharide 32 in 78% as a pure β-diastereomer [70]. Schmidt demonstrated the usefulness of xylylene tethers in application to the iterative synthesis of maltotriose [70]. In this application, the xylylene tether was used to link two glucose

• liberating the hydroxy group at C-4’ gave the tethered donor–acceptor combination 36. After the NIS/TfOH-promoted glycosylation the desired trisaccharide 37 was obtained in 75% yield as a pure α-linked diastereomer. The per-acetylated maltotriose target was obtained after palladium-catalyzed hydrogenation

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• milling time, analysis of the reaction mixture by 1H NMR spectroscopy showed no product formation. Moreover, under the standard reaction conditions, it was observed that the model compound threo-1b reacted slower in comparison to its diastereomer erythro-1a. After 2 h of milling, the product threo-3b was

• could be isolated in 89% yield (Scheme 3). On the other hand, its diastereomer threo-1d was much less reactive and only trace quantities of threo-3d could be isolated. This difference in reactivity, which follows the trend previously observed for the pair erythro-1a and threo-1b, could have stemmed from

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

• known configuration. Intriguingly, salt water fish-infesting M. marinum produces a remote diastereomer [60] of mycolactone F (dia-mycolactone F, 9) that exhibits the regular configuration of the 1,3-diol motif at the end of the lower side chain [61]. Most recently, the Kishi laboratory isolated two new

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

• these compounds and notably reported that TES was better than TMS for efficient separation of both isomers, resulting in an improved 42% yield for the isolated major diastereomer (5’R)-11ab [12]. Then, subsequent acidic hydrolysis afforded (5’R)-16 and (5’S)-16 and alkyne desilylation under basic

• ’S)-17 (Figure 3). As observed for compound 16, the H-1’ chemical shift is more shielded for (5’S)-17 isomer (doublet (3JH-1’-H-2’ = 6.0 Hz) at 5.98 ppm) than for the (5’R)-17 diastereomer (doublet (3JH-1’-H-2’ = 7.0 Hz) at 6.04 ppm). Similarly, the H-4’ chemical shift is more shielded for (5’S)-17

• isomer (triplet (3JH-4’-H-3’ = 3JH-4’-H-5’ = 3.5 Hz) at 4.03 ppm) than for the (5’R)-17 diastereomer (triplet (3JH-4’-H-3’ = 3JH-4’-H-5’ = 2.5 Hz) at 4.07 ppm). Moreover, chemical shifts for H-3’ (doublet of doublet (3JH3’-H2’ = 5.5 Hz, 3JH3’-H4’ = 2.5 Hz) at 4.30 ppm) and H-2’ (doublet of doublet (3JH2

Phenylsilane as an effective desulfinylation reagent

• Wanda H. Midura,
• Aneta Rzewnicka and
• Jerzy A. Krysiak

Beilstein J. Org. Chem. 2017, 13, 1513–1517, doi:10.3762/bjoc.13.150

• a continuation of our studies on asymmetric cyclopropanation of vinyl phosphonates using (S)-dimethylsulfonium(p-tolylsulfinyl)methylide and its further application. It was formed as a single diastereomer with full stereoselectivity. To determine the relative configuration of the obtained structure

• silane procedure led to the single diastereomer 7a. In this case determination of the relative configuration as trans was based on a high coupling constant 3JP-H = 17.0 Hz, which evidenced retention of configuration during the desulfinylation process (Scheme 2). The reaction conducted under solvent-free

• phenylsilane utilizing the procedure described above and afforded phenylacetate 8 as the only product. Methylation of 9 afforded product 10 with full stereoselectivity as the only diastereomer although the configuration of this center was not determined. Also in this case treatment with PhSiH3/KOH caused a

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

• temperature. As it also facilitated the isolation of the tetrahydroisoquinolonic acid product, it was chosen to study the CCR of 9a–t. The latter tend to precipitate in a pure form (often as a single diastereomer) from the reaction mixture and can be conveniently isolated by filtration. This prior observation

• major diastereomer was shown to possess the (RS,RS)-configuration (vide infra) and is referred to as ‘anti‘ throughout this article (considering orientation of carboxylic group relative to C11a–C12 bond of the five-membered ring); the minor, (RS,SR)-configured diastereomer is referred to as ‘syn

• ’ (Figure 4). A good to excellent yield of pure anti-diastereomer was obtained with 9a,b, 9d, 9j, 9l, 9n,o (Table 1, entries 1, 2, 4, 10, 12, 14 and 15) by simple filtration. We have also shown that in some of these cases (Table 1, entries 1 and 2) an additional quantity of anti- and/or syn-configured CCR

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

• chiral HPLC analysis of major diastereomer. The dr values were determined by 1H NMR analysis. Method A: with 10 mol % of d as a catalyst, −20 °C, 12 h. Method B: with 10 mol % of d as a catalyst, −10 °C, 24 h. A plausible mechanism. Optimization for the reaction conditionsa. Supporting Information

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

• ], and aryl thiols [75][76] can be formed in moderate to quantitative yield with the 1,2-trans diastereomer prevailing in all instances (Scheme 23) (also partially reviewed in Noguchi et al. [70]). The substrate scope was extensive in all instances and included successful glycosylation of up to

• to provide the 1,2-trans β-diastereomer. Only in pathway A, by direct nucleophilic displacement of the β-activated complex, does the minor α-diastereomer form. To demonstrate the potential utility of this methodology in labeling strategies, the Shoda group has also accessed fluorescent thioglycosides

• -alkynyl acceptors) or Et3SiH (alkynyl acceptors). In all cases the yields were very good and the stereoselectivity pretty good for the 1,2-cis glycoside diastereomer. The mechanism is thought to proceed through an initial hydrogenolysis of the benzyl groups to produce a reactive dihydroxytriazinyl

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

• coupling, acetate protection of the newly generated hydroxy group and DBU-mediated elimination. This three-step sequence proceeded as shown in Scheme 6 with excellent yields (94%) giving the triene 33 as a single diastereomer, which demonstrates the usefulness of aldol condensations in complex target

• alcohol 60. In this Δ5,6-trans-selective reaction the desired anti-diastereomer could be isolated in 85% with a dr of 6:1, which presumably arises from a chelation-controlled stereoselectivity [89]. The aldehyde 59 itself can be prepared in two steps from the corresponding Roche ester [90]. After

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• yield was 52% in three steps and the product purity was excellent. Two key diastereomers were prepared with efficient and direct access to the α-C-arylglucoside. Keywords: arylzinc derivative; β-C-arylglucoside; diastereomer impurity; ipragliflozin L-proline; stereoselective synthesis; Introduction

• was purified by recrystallization from methanol, and the desired product in 65.3% yield with HPLC purity 99.79% was obtained; the diastereomer 5’ was not detected. The protecting groups of 5 were removed in presence of sodium methoxide in refluxing methanol, and then recrystallized to give

• , 115.7, 73.1, 70.6, 68.4, 62.1, 38.7, 30.0, 27.0; MS (ES+) m/z: 763.44 [M + Na]+. Structure of ipragliflozin L-proline. Stereoselective synthesis of C-aryl glycoside by Lemarie. Stereoselective synthesis of β-C-arylglucoside 5. Synthesis of 1. Synthesis of diastereomer 6’ and 5’. Conditions for the