Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• described to give β-hydroxylactones with high diastereoselectivities. The stereoselectivity of this cyclization is highly solvent dependent and can give syn- or anti-β-hydroxylactones with high diastereoselectivity. This methodology was also applied to the synthesis of a chiral necic acid lactone which is a

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• stereoselectivity is possible through the conformation of 14 where the OTBS group is in pseudoequatorial position (Scheme 2). Therefore, the Pauson–Khand reaction proceeded to afford 11 containing an α-H at C6. From this intermediate, to our delight, the stereoselective attachment of the requisite methyl group

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• : compound 3, thiazolooxazol-1-one I and AY in the reducing stereocenter in an ratio of 3 to 1. The mechanistic process indicates that the configuration of ʟ-cysteine didn’t affect the stereoselectivity in the formation of compound 5 and 7. Thus, we further validated the hypothesis through the experimental

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• catalysts were designed that showed substrate selectivity, turnover, regioselectivity, and stereoselectivity [5][6][7][8][9][10][11][12][13][14]. Supramolecular architectures with an internal cavity are potential candidates to work as supramolecular catalysts [5][6][7][8][9][10][11][12][13][14]. The first

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• reported extensive studies on the regio-and stereoselectivity of nitroso Diels–Alder reactions between various nitroso derivatives and functionalized dienes [23]. These studies led to the selection of enol phosphates as ketone precursors for the diene functionalization. Enol phosphates display several

• , we have shown that the Wightman reagent 6, a chiral chloronitroso derivative [27], led to a complete regio- and stereoselective reaction with functionalized dienes (Scheme 1). The chiral auxiliary contributes to both regioselectivity and stereoselectivity. After hydrolysis of the chiral auxiliary and

• gave a reproducible 46% yield of 23. Optimal conditions were obtained using 1.8 equivalents of vinyl iodide and 1.7 equivalents of BuLi (Table 2, entry 6). It was difficult at this stage to determine the stereoselectivity of the coupling reaction since the starting acetal in 20 was a mixture of

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• successfully prepared [32]. The protocol, using NaI as a catalyst and K2S2O8 as an oxidant, tolerated a broad range of substrates with good stereoselectivity. Interestingly, structurally related benzothiazine derivatives with a carboxylic function in the C-3 position are only seldomly described in the

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• acids. One-pot combination of the reductive ring opening and subsequent addition of thiols allows obtaining the cysteine derivatives in practical yields and with high stereoselectivity at the removed β-stereocenter. Keywords: amino acids; cathodic cyclopropane opening; cysteine derivatives; Ni–Schiff

• cyclopropane ring in α,α-cyclopropanated amino acids yielding the cysteine derivatives in practical yields and with high stereoselectivity at the removed β-stereocenter. Thus, the present paper is a further development of the extended research on electrochemically induced stereoselective transformations in the

• amount of the alkene (48% instead of 20% detected in entry 5) was also isolated from the reaction mixture). Thus, the experiments indicated that the one-pot multistep experimentally simple procedure allows achieving high stereoselectivity at the removed β-stereocenter, what is not an easy task. In all

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• anode-free electrochemical protocol for the synthesis of pinacol-type vic-1,2-diols from sec-alcohols, namely benzyl alcohol derivatives and ethyl lactate. The corresponding vic-1,2-diols are obtained in moderate to good yields, and good to high levels of stereoselectivity are observed for sec-benzyl

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• , substrates with a differently substituted indole ring or with different protecting groups on the indole N-1 position (2f, 2g). All substrates reacted smoothly to give the corresponding products in moderate to good yields and with high stereoselectivity. It should be pointed out that the minor products 2a’–e

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• experimentally observed stereoselectivity. Keywords: azomethine ylides; cycloaddition; cyclopropenes; DFT calculations; spiro heterocycles; Introduction Spiro compounds (molecules containing at least two rings with only one common atom) are an important class of both synthetic and naturally occurring

• diastereofacial stereoselectivity. Our goal was to identify the nature of transition states associated with two theoretically possible diastereomers and to find out if the experimentally observed diastereomer is more kinetically favorable than the opposite one. The reaction between 3-methyl-3-phenylcyclopropene

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• catalysts has been successfully developed employing dynamic metal–ligand coordination bonds. While only a small fraction of these 3D architectures was useful for chiral catalysis, an even smaller fraction was able to provide a high stereoselectivity during asymmetric catalysis [5]. For instance, an

• sites and an appropriate asymmetric cavity is the key for the enhancement of catalytic activity and stereoselectivity [75]. Strictly speaking, the above example does not contain fully dynamic heteroleptic metal fragments, as the aryl–Pt bond is not kinetically labile. Nevertheless, the example

• hydride species 49 that is well known for hydroformylation reactions [77]. Incorporation of the monoligated catalyst into the confined cavity of the capsule showed very good catalytic activity towards the hydroformylation of styrene (50, Figure 11) with a high stereoselectivity (65% ee) at 32% conversion

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• thiol. This generates a new stereocenter in the α-position, which takes place under the chiral environment of the BINOL-based macrocycle. However, the hydrogen abstraction takes place with little stereoselectivity, so that both diastereoisomers are formed in almost equal amounts (er = 53:47, see Figure

• , rotaxane (R)-38 was obtained in 35% overall yield (see Figure 8b). These rotaxanes where then used as catalysts for the asymmetric benzoin condensation of benzaldehyde (39). The best yield (90%) could be generated at 0 °C in methanol with 10 mol % of catalyst (R)-35a, albeit with a low stereoselectivity

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• on the reaction stereoselectivity. The cyclohexanediamine-linking macrocycles M1–M4 afforded the product with overall higher enantiomeric excess (ee) (Table 1, entries 1–4). Among which the isopropyl-substituted macrocycle M3 gave the best selectivity, i.e., 42% ee. This suggested a suitable crowding

• out to be better. A suitable reaction concentration (0.1–0.2 M) was found to be important. A very high or low reaction concentration led to decreased stereoselectivity probably due to the existence of catalyst aggregation or background reactions (Table 3, entries 8–10). Substrate scope Having

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• /mol to form IN1f via 1fTS2f. Although the calculated barriers are not prohibitively high, they are much greater than the exo-hydrometalation pathway. These results suggest the reaction’s stereoselectivity originates from the imposed steric constraints of the more-hindered endo-face. Based on the

• determined the stereoselectivity of the reaction arises from the unattractive interactions imposed from the sterically hindered endo-face of the bicyclic alkene. The mechanistic insights gained from this combined experimental and theoretical study will facilitate further future methodology development in

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• room temperature. The results are summarized in Table 1. We were pleased to find that the domino Michael addition/cyclization reaction could complete in the presence of 5 mol % C1 at room temperature in 12 h providing the desired product 3aa in 55% yield with excellent stereoselectivity (>20:1 dr, 97

• % ee) (Table 1, entry 1). Due to the excellent stereoselectivity of the target product 3aa, the reaction conditions were further optimized to increase its yield. Subsequently, a number of organocatalysts (Figure 3) were evaluated for this domino process (Table 1, entries 2–8). From the experimental

• thiourea catalysts (C4–C7) can catalyze the reaction to obtain higher yields while keeping the stereoselectivity basically unchanged. Then we chose the C4 catalyst with the best reaction effect as the optimal catalyst to explore the influence of other reaction conditions such as solvent type and catalyst

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• -dienylmagnesium reagents 33 with high regio- and stereoselectivity (Scheme 6) [68]. A major problem with the carbomagnesiation of internal alkynes bearing no heteroatoms is the relatively harsh conditions required producing poor selectivity in some cases [69][70]. The strong σ-donating nature of the IEt2Me2NHC

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• desired epoxide 5 in an acceptable 70% yield with excellent stereoselectivity as the sole syn isomer (dr > 95:5). It is worth noting that a small quantity of pyridine was added to prevent unwanted acid-catalyzed epoxide hydrolysis [31]. The stereochemistry of 5 was assigned later after pyrrolidine ring

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• of a wide range of axially chiral biaryls, heterobiaryls, vinylarenes, N-arylamines, spiranes, and allenes with high efficiency and excellent stereoselectivity. Keywords: allenes; atropisomerism; axial chirality; chiral phosphoric acid; heterobiaryls; spiranes; Introduction Axial chirality is one

• poor chemoselectivity [40]. However, the realization of this redox-neutral aryl–aryl cross-coupling is a formidable challenge. Therefore, the discovery of efficient catalysts and ligands to achieve high stereoselectivity is a fundamental issue in catalytic asymmetric synthesis [14]. In this section, we

• functional calculations showed that the chiral phosphoric acid proton forms an H-bond with nitrogen atoms of 1 and the phosphate acts as a chiral counterion, resulting in a [3,3]-sigmatropic rearrangement with controlled stereoselectivity [14][41]. In 2017, Tan and co-workers developed an organocatalytic

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• ; separation of racemic nucleosides; stereoselectivity; Introduction Among all the biomolecules in an organism, nucleic acids, namely DNA and RNA, have the unique role of storing the genetic code – the nucleotide sequence that specifies the amino acid sequence of proteins that is essential for life on Earth

• to treat HIV infection [58] as well as human chronic hepatitis B [59]. Using asymmetric synthesis or resolution with appropriate enzymes to prepare these enantiopure 1,3-oxathiolanes has gained extensive attention due to the good stereoselectivity, high efficiency, mild reaction conditions, and eco

• stereoselectivity during β-selective glycosidic bond formation. The general pathway for glycosidic bond formation (Figure 4) shows that the glycoside donor moiety has to be activated using an appropriate activator to form an oxonium ion. The attack of a nucleobase (glycosyl acceptor) may occur on either side of the

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• of the reaction was studied (Table 1). The use of Pd(PPh3)4 resulted in the formation of isomeric products 2aa and 3aa in a 93:7 ratio (Table 1, entry 1). Other catalysts led to significant loss of stereoselectivity on the double bond (Table 1, entries 2–9). When Pd(dppf)Cl2 was employed, isomeric

• study. Substituted phenylboronic acids and vinyl triflates led to the formation of enamides 2 with high stereoselectivity and in good to high NMR yields (Scheme 2). However, isolated yields were found to be lower due to the decomposition of the formed enamides 2 during column chromatography on silica

• catalyst dependent. The use of Pd(PPh3)4 led to the selective formation of enamides 2 with retention of configuration of the double bond. Reactions with other catalysts provided significant losses of stereoselectivity on the double bond. When Pd(dppf)Cl2 was used, enamides 3 with inversion of the

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• , including enantioselective H-bonding-catalyzed additions to aliphatic N-Boc-imines with high stereoselectivity [22]. A broad range of β-aminonitroolefins were reduced to chiral β-aminonitroalkanes in high yields and excellent enantioselectivities using trichlorosilane as a reducing agent and an N

• . Sulfinylurea catalysts were more active than the corresponding thioureas. The additional stereogenic center on the sulfur plays only a minor role on the stereoselectivity of the reaction, which is governed mainly by the configuration of the proline moiety. DFT calculations elucidated the stereochemical action

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• good yields (24 to >99%) with poor to moderate ee (9 to 55%). A complete reversal of stereoselectivity was observed on introducing a benzoyl group in cinchonine and cinchonidine. It was demonstrated that racemization occurred in suitable solvents under mild conditions due to retro-MR of the initially

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• the previously arranged MOMCl, as the MEM functionality was found to have a better impact on the stereoselectivity of the later cyclopropanation reaction. Thus, the MEM ether 52 was obtained in 95% yield and subjected to in situ prepared dimethyl sulfoxonium methylide at low temperature to affect the

• vinylmagnesium bromide. The allylic alcohol products 71 and 72 were obtained as a diastereomeric mixture in 86% yield with poor stereoselectivity. To gain more of the desired diastereomer 71, the mixture of 71 and 72 was subjected to a two-step procedure involving a Dess–Martin oxidation followed by

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• stereoselectivity. However, neither isopropyl or neopentyl benzylic ethers 26 and 27 [23][24] led to a significant change in the E/Z ratio for cinnamylamine 23 (Scheme 11). Conclusion In summary, we report a new, convergent access to allylic alcohols and amines. The process proceeds by selective cross-coupling of α

• -lithio terminal epoxides or N-Bus-aziridines with α-lithio ethers. Where 1,2-disubstituted alkenes are generated the E/Z stereoselectivity is modest, and preliminary results suggest the size of the leaving group does not play a significant role. However, the geometry of alkene formation might be

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• carbohydrate alkene precursor 7 and Hg(OAc)2 proceeds with high stereoselectivity to give the α-ᴅ-C-glycopyranosyl derivative (1,5-trans-isomer) 8 as a single isomer [41]. Treatment of compound 8 with sodium borohydride (NaBH4) under phase transfer conditions (PTC) yields compound 9 as the only product. The

• manner as reductive elimination forms during the mercury removal process (Scheme 6). Mercury(II) salts had been effectively used to synthesize five-membered furanose derivatives with high stereoselectivity. Nicotra et al. developed Hg(OAc)2-mediated cyclization of hydroxy-alkene derivative 15 to form α-ᴅ

• 1.4 equiv of Hg(OAc)2 and sodium bromide (NaBr) at room temperature, then β-ᴅ-arabinose derivative 18 was formed as the major product (Scheme 8) [45]. The high stereoselectivity of β-derivative 18 at the anomeric position was predominantly due to the presence of the benzyl groups at the C-2 and C-3