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

• of the Boc-protecting group with the Teoc group then gave phenol 136. Compound 136 was then subjected to a highly diastereoselective oxidative phenolic coupling giving fused tetracyclic architecture 137. Follow-up acid-mediated intramolecular aza-Michael addition and subsequent alkene reduction

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• diastereoselective reactions on acyclic systems is often difficult due to small energy differences between reacting conformers. In the case of our trapping reaction of chiral imidazolyl enolates, the lack of diastereoselectivity may be associated with the presence of an E/Z mixture of enolates. This would also

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

• imines or their synthetic equivalents. Furthermore, we wanted to develop an enantioselective and diastereoselective process without adding chirality elements within the reagents. For our initial studies, we have selected the well-studied cyclic enones as substrates and the Taniaphos ligand (L14) that has

• conjugate addition of trialkylaluminum or Grignard reagents was realized only in an achiral manner, this work merits discussion here. Aluminum and magnesium enolates were alkynylated with ethynylbenziodoxolone (EBX). This diastereoselective electrophilic alkynylation afforded the corresponding α

• enantioselective tandem borylation/intramolecular aldol cyclization procedure (Scheme 37) [78]. The desymmetrization process of cyclic diones 147 gave the densely functionalized bicyclic products 148 with four contiguous stereocenters usually in a highly diastereoselective fashion. Presumably, the difference in

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• . Recently, also regio- and diastereoselective carbometalation of easily accessible trifluoromethyl-substituted cyclopropenes to access trifluoromethylcyclopropanes has been reported (Scheme 1A) [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. In contrast

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

• ; however, the methodology was not applied to bicyclic alkenes. In 2019, the Yang lab examined the Cu-catalyzed diastereoselective 1,2-difunctionalization of oxabenzonorbornadienes 30 for the synthesis of β-thiocyanato thioethers 68 (Scheme 12) [46]. In contrast to the previous difunctionalization reactions

• catalysts, iron is bringing a renaissance to the idea of sustainable, green catalysis. In 2011, Ito et al. reported a diastereoselective Fe-catalyzed carbozincation of heterobicyclic alkenes 1 with diphenylzinc (74a) (Scheme 13) [47]. Using an ortho-phenylene diphosphine ligand L3, the authors were able to

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• -catalyzed trifluoromethylthiolation of α-arylacrylamides derived from 8-aminoquinolines 29 by C–H bond activation (Scheme 13) [104]. Using the Munavalli reagent V as an electrophilic SCF3 source, this diastereoselective method selectively led to the formation of Z-isomers and turned out to be robust (not

• was used as solvent. Cp*Co(III)-catalyzed ortho-trifluoromethylthiolation of 2-phenylpyridine and 6-phenylpurine derivatives described by Yoshino and Matsunaga [125]. aWithout AgSbF6. b2.0 equiv of VII, 10 mol % of AgOAc and 30 mol % of Gd(OTf)3 were used instead of AgSbF6. Diastereoselective

• on aliphatic amide derivatives derived from 8-aminoquinoline by palladium-catalyzed C–H bond activation described by Besset and co-workers [126]. Product 32d was contaminated with 10% of an inseparable impurity. Regio- and diastereoselective difluoromethylthiolation of acrylamides under palladium

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

• a 1,5-anti induction of the aldol reaction [18][19][20] based on chiral alkoxy partner 9. Furthermore, it could be envisaged to reduce the resulting β-hydroxyketone 7 in a diastereoselective manner to obtain a 1,3-diol. This synthetic strategy could thus bring new stereochemical opportunities to

• 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

• -citronellene (10). Synthesis of fragment 8 from ʟ-cysteine ethyl ester hydrochloride (16). Synthesis of fragment 21 through a stereoselective aldol reaction. 1,3-Anti-diastereoselective reduction of 21 with PNBz transposition, and final determination of the relative stereochemistry by NOESY experiment on 25

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

• proposed to occur by hydroboration of the carbonyl compound 53 with BH3, followed by B‒O/B‒H transborylation with HBpin (ΔG‡ = 24.5 kcal mol−1), to give the alkoxy boronic ester 56 (Scheme 13). Nicholson, Thomas and co-workers reported the H-B-9-BBN-catalysed diastereoselective reductive aldol-type

• carbonates and the proposed mechanism. H-B-9-BBN-catalysed reductive aldol-type reaction and the proposed mechanism. H-B-9-BBN-catalysed diastereoselective allylation of ketones and the Ph-BBD-catalysed enantioselective allylation of ketones and the proposed mechanism. H-B-9-BBN-catalysed C–F arylation of

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• synthesis by Taber that used dichromate as an oxidant [13] led to a less diastereoselective reaction furnishing the three ketones 9, 10, and 11 in a ratio of 36:2:5. The cis-conformation of the decalin backbone of 9 and 11 originates from the endo-selectivity of the Diels–Alder reaction and the boat

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• , protection of the secondary alcohol as a benzyl ether, oxidation of the sulfur and Pummerer rearrangement (Scheme 3). A Wittig reaction gave compounds 8, as a 10:1 separable diastereomeric mixture. A diastereoselective Diels–Alder cycloaddition followed by oxidation of the resulting epimeric mixture gave

• TBS deprotection giving the bicyclo[3.2.1]octane subunit with a good yield of 74%. A sequence involving diastereoselective reduction of ketone 24 with SmI2, Appel reaction to convert the primary alcohol to the corresponding primary alkyl iodide followed by a MOM protection of the secondary alcohol

• by diastereoselective cycloaddition followed by C15–C16 epoxidation with m-CPBA. Reductive cleavage of the O–O bond by Zn/AcOH treatment afforded epoxide 53 as a single diastereomer in two steps and 65% yield. The correct bicyclo[3.2.1]octane was obtained by Wagner–Meerwein epoxide rearrangement

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

• one-pot reactions with recyclable organocatalysts [69]. Notably, we conferred K10 acid to promote the C–H activation in the synthesis of spirooxindolepyrrolidines, and used Zeolite HY catalyst to synthesize diastereoselective dispiro[oxindolepyrrolidine]s with a butterfly shape (Scheme 1A and 1B) [70

• introduced in this study. Subsequently one equivalent of aldehyde and olefinic oxindole in situ were followed by decarboxylative 1,3-dipolar cycloaddition for diastereoselective synthesis of spirooxindolepyrrolothiazoles with generating 5 new bonds, 5 stereocenters and two heterocycles (Scheme 1C and Scheme

• diastereoselective spirooxindolepyrrolothiazoles by the formation of two new rings, 5 bonds, and 5 stereocenters without intermediate purification. To explore the reaction scope of 4-CR, different aldehydes 1 (Ar1) were used to react with ʟ-cysteine (2) and olefinic oxindole 4a in the synthesis of substituted

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• , Perm 614990, Russian Federation 10.3762/bjoc.18.162 Abstract There has been developed an easy synthetic approach to spiro[dihydrofuran-2,3'-oxindoles] via a highly diastereoselective formal [4 + 1] cycloaddition reaction of [e]-fused 1H-pyrrole-2,3-diones with diazooxindoles. The described novel

• ] (Scheme 1). Thus, in the present work, we report a simple, catalyst-free diastereoselective method for the synthesis of dihydrofurans spiro-annulated with an oxindole moiety for the first time. The essence of the method is the use of [e]-fused 1H-pyrrole-2,3-diones (FPDs) as the enone component in a

• the same diastereomer 3ia with a good 54% yield. Conclusion To conclude, we have developed a facile synthetic approach to spirofuranoxindoles 3 via the highly diastereoselective formal [4 + 1] cycloaddition reaction of FPDs 1 with diazooxindoles 2. The obtained compounds 3 were found to be stable

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

• the synthesis and properties of such BINOL-based chiral MIMs, together with their use in further diastereoselective modifications, their application in asymmetric catalysis, and stereoselective chemosensing. In their minireview, Prodip Howlader and Michael Schmittel [22] highlighted the recent results

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• derived from biomass pyrolysis, due to its reactive functionality, and the chirality which derives from glucose [4][5][6][7]. Reactions of 1 where the α,β-unsaturated ketone participates as an electrophile are usually completely diastereoselective, as the approach of the nucleophile is controlled by the

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• polycarbonyl compounds such as vic-diketoesters has been investigated in depth by Wasserman, Parr [2] and Gleiter, Rubin [3]. Important contributions for the use of α,β-diketoesters in stereoselective transformations came from Doyle’s group [4][5]. One remarkable example is the diastereoselective

• . Oxidation of the latter compound to the α-keto-β-hydroxy ester IV using DMDO and subsequent heating in PhCF3 triggered an α-ketol rearrangement which led to ketol V. Diastereoselective reduction gave α,β-dihydroxyester 35 which was converted to (−)-jiadifenoxolane A (36) in five further steps. Palau’amine

• reagents. The presented examples may encourage the use of vicinal ketoesters in future applications, in particular in the field of natural product synthesis. Structures of vicinal ketoesters and examples for their typical reactivity. Doyle’s diastereoselective intramolecular aldol addition of α,β

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• , Russian Federation 10.3762/bjoc.18.109 Abstract A practically convenient and streamlined protocol for the trans-diastereoselective introduction of an aryl substituent at position 4 of the 1,4-dihydroisoquinol-3-one (1,4-DHIQ) scaffold is presented. The protocol involves direct Regitz diazo transfer onto

• ) transformation resulted in the highly diastereoselective formation of C-arylation products 10 which in some cases was accompanied by a regioisomer formation (with respect to the entering arene moiety) and the formation of 3-isoquinolones 15 (isolated and characterized in several instances). Not unexpectedly

• summary, we have presented a practically convenient and streamlined protocol for the trans-diastereoselective introduction of an aryl substituent at position 4 of the 1,4-dihydroisoquinol-3-one (1,4-DHIQ) scaffold. The protocol relies on hitherto undescribed direct Regitz diazo transfer onto readily

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• ][29][30]. For example, Han and co-workers successfully developed a tetrabutylammonium fluoride-catalyzed cycloaddition of phenacylmalononitriles and nitroolefins for the diastereoselective synthesis of multifunctionalized cyclopent-2-ene-1-carboxamides [31] (reaction 1 in Scheme 1). Liu and Ban

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• from P-(chloromethyl)amide precursors 92a and 92b through intramolecular Friedel–Crafts alkylation. Synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N’-diallyl-vinylphosphonodiamides. Diastereoselective synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N

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

• highly chemo- and diastereoselective manner and brought about the formation of 3-azabicyclo[3.1.0]hexane cycloadducts 3d and 3e in 69% and 91% yields, correspondingly (Scheme 3). As shown by these experiments, the cyclopropene double bond demonstrates higher reactivity compared to exocyclic double or

• diastereoselective approach for the synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane through cycloaddition reactions of a stable azomethine ylide – protonated Ruhemann's purple to cyclopropenes. The cycloaddition reaction is compatible with a broad scope of cyclopropenes. DFT calculations

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

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

• '-binaphthyl-2,2'-diol (BINOL) unit as a stereogenic element in mechanically interlocked molecules (MIMs). We describe the synthesis and properties of such BINOL-based chiral MIMs, together with their use in further diastereoselective modifications, their application in asymmetric catalysis, and their use in

•  6a). Subsequently, Takata and co-workers presented a highly diastereoselective synthesis of [2]rotaxane amine N-oxides via intercomponent chirality transfer (see Figure 6b) [53]. For the synthesis of the rotaxanes, complexes of hydroxy-terminated ammonium salts 28a–d and BINOL-based macrocycle (R)-12

• (DMDO) was used to obtain the corresponding amine N-oxides (R,R/S)-30a–f in 80–99% yield. This oxidation takes place inside the chiral macrocycle, so that the resulting stereogenic nitrogen is formed in a diastereoselective fashion. Interestingly, for rotaxanes (R,R/S)-30a–c, which feature C3/C6/C12

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• under base-catalyzed conditions towards the formation of densely substituted dispirocyclopentanebisoxindole derivatives. The reaction proceeded in a diastereoselective manner to afford four chiral stereocenters. The method also has advantages of wide substrate scope, readily available starting materials

• operation without chiral catalyst is still an atom-economical and operationally simple procedure to demonstrate the construction of dispirooxindoles. In the recent years, the diastereoselective construction of dispirocyclopentanebisoxindoles consisting of two spirooxindole motifs has acquired attention from

• dimerization produces dispirocyclopentanebisoxindoles in a transition-metal-free protocol (Scheme 1). Results and Discussion There is extensive application of 3-phenacylideneoxindoles generating diverse reaction strategies following the regioselective and diastereoselective synthesis of carbocyclic and

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• oxindole-based α-aminoboronates. The asymmetric synthesis of diverse α-aminoboronic acids by diastereoselective Cu(I)-catalyzed borylation of N-tert-butanesulfinyl aldimines was described by Ellman and co-workers for the first time in 2008 [15] and next further developed with a more stable Cu(II) catalyst

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• reagent [9][10][11], and phenylsulfonyl group transfer reagent [12][13]. In the field of mechanochemistry, the usefulness of N-fluorobenzenesulfonimide has been exemplified in the asymmetric fluorination of β-keto esters (Scheme 1a) [14], and in diastereoselective fluorinations (Scheme 1b) [15], which

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• afforded the same major diastereoisomer but opposite enantiomers (Scheme 3, 3q). The diastereoselectivities were similar for the isomers. Since the diastereoselectivity of the reaction was low, we attempted to increase the ratio of diastereoisomers via enolisation followed by diastereoselective protonation