Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• stereoselectivity is also explained. Keywords: asymmetric; aza-Friedel–Crafts reaction; H-bonding; organocatalysis; stereoselectivity; Introduction The ease of a chemical transformation depends on the thermodynamic instability of a chemical bond owing to its fast cleavage under mild reaction conditions. A C–H

• nitrogen and the catalyst which selectively blocks one face of the imine’s plane. This forces the nucleophile to approach from the opposite face thus imparting stereoselectivity into the products. The first organocatalyzed asymmetric aza-Friedel–Crafts protocol was published by Terada and co-workers in

• . Stereoselectivity in the products 10/11 was achieved by using the chiral spirocyclic phosphoric acid catalyst P3 which, through H-bonding interactions with the nucleophile and the electrophile, forces the nucleophile to approach the C=N plane from the Re face. In general, enantiocontrol with pyrroles was better

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• to furnish the transient complex 81 which undergoes σ-bond metathesis to give the product 77 and regenerating 78 (Scheme 16b). While speaking regarding the alkenylation, the geometrical isomerism, i.e., the stereoselectivity between the cis- and trans-alkenylation, has not been considered so far

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• investigate the influence of various fluoride scavengers as additives in the three-component process [25][26]. An extensive study (not shown), revealed that most common scavengers either led to a decreased yield, a decreased stereoselectivity or a combination of both. Yet a combination of CaCO3, tartaric acid

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• -methoxyphenyl (PMP)-protected imines 21 (Scheme 6A). By varying the reaction conditions, the syn-anti and the syn-syn diastereomers can be prepared with good yields and excellent stereoselectivity. Using nitroacrylate 23, the authors have also demonstrated a tandem conjugate addition/nitro-Mannich/lactamization

• secondary amine 157 generated in the cyclization step (Scheme 40B). Consequently, the complex tetracyclic compound 158 was produced in 47% yield and with good stereoselectivity (84% ee, dr 7.5:1). At about the same time, comparable results were reported by the group of Zhang [82]. Their Cu-catalyzed cascade

• enolate with various aldehydes provided the aldol adducts with good yields. Compared to general aldol reactions, the boron enolates showed lower reactivity and required overnight reflux to achieve good conversions. Nevertheless, the stereoselectivity of the reaction was still excellent (up to >95% ee, dr

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• thermodynamically controlled stereoselectivity as compared to the parent Belokon complex. Additionally, functionalization with the tert-butyl group significantly enhances the reactivity of the deprotonated glycine complex towards electrophiles as compared to the anionic species formed from the original Belokon

• ]. Functionalization of the phenyl ring in the benzophenone gives rise to an additional axial chirality (L3), thus improving stereoselectivity observed at the removed stereocenter [24][25]. Replacing N-benzylproline for 2,7-dihydro-1H-azepine (L5) allowed obtaining a new tridentate ligand with chemically stable axial

• Michael acceptor. A number of thiols was taken as the model compounds. The reaction was performed under thermodynamic conditions reported in [41], to compare the thermodynamically controlled stereoselectivity of L7 and L1. The use of a 2 molar excess of K2CO3 induces the equilibrium between the isomers

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• ; Introduction Transannular cycloaddition reactions (TCRs) are useful for the synthesis of complex natural products and other biologically active compounds with high efficiency and stereoselectivity [1][2][3][4]. There are several different ways in which TCRs can occur, depending on the nature of the starting

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• ball mill synthesized bifunctional catalyst 5bm, again with slightly diminished yields and conversions. Application of the ball mill-synthesized complex 5bm in the alkyne semihydrogenation of tolane (12) gave (Z)-stilbene (13) with full stereoselectivity in good yield (86%, Scheme 3b). Noteworthy, the

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• thiazolidinone ring, possibly leading to a strong conformational distortion of Mosher's model. The question of the resulting stereoselectivity was thus left open for later resolution. To complete this study, the 1,3-anti-diastereoselective reduction of β-hydroxyketone 21 was undertaken through the Evans

• stereopentade, in view of designing molecular tools for biological purpose. The reduction took place in 76% yield with complete stereoselectivity. However, a mixture of two inseparable products was obtained, containing the expected but minor alcohol 22 (10%), and more surprisingly the major isomer 23 (66

• stereoselectivity. Starting from the chiral pool bringing the 8-methyl substituent, the secondary alcohol on C-11 was stereoselectively introduced by the Krische allylation of alcohol 11. The next key step consisted in an aldol reaction of ketone 15 onto aldehyde 8, which proceeded with a high stereocontrol

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• transformations using group 13 exchange from alkene functionalisation to carbonyl reduction. The subtle differences in reactivity of the group 13 catalysts were used to enable unique catalytic reactivity and/or reaction chemo- or stereoselectivity, including cases where the stoichiometric reaction was rendered

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

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