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

• rigid bicyclic framework. Secondly, through ring opening of the bicyclic framework; the C–X bond of a heterobicyclic alkene is much weaker than the corresponding C–C bond of a homobicyclic alkene, which allows the C–X bond to be readily cleaved over the course of a reaction. The stereochemically well

• elimination (Figure 2b, Hb); however, their elimination would generate a highly unstable alkene at the bridgehead, violating Bredt’s rule [9]. For these reasons, carbobicyclic alkenes have been exploited as propagation mediators, as seen in Catellani-type reactions [10][11][12]. In this review, we will focus

• initiates with the in situ reduction of Ni(II) to Ni(0) followed by the side-on coordination of the alkene and alkyne substrates to the metal center with subsequent oxidative cyclometallation to form a nickel metallacycle, similar to several reported Ni-catalyzed [2 + 2] cycloadditions [29][30]. Rather than

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

• a negative charge. While both reacting C–N–N systems fulfil the requirements to give a cycloaddition with an alkene; which are (i) electron density default on the carbon atom and (ii) an electron density excess on the nitrogen atom; the overall positive charge of the hydrazone moiety forces a role

• inversion of the reagents and whereas in the classical cycloadditions with azomethine imines, they act as a nucleophile (involving their HOMO, interacting with the LUMO of the alkene), in our case, the protonated hydrazone acts as an electrophile (involving their LUMO, interacting now with the HOMO of the

• alkene) (Figure 2). Thus, we can consider the reaction of hydrazones with alkenes an inverse-demand cycloaddition with respect to that of azomethine imines (Figure 2). In fact, we monitored the global electron density transfer (GEDT) [34] between the reagents along the reaction coordinate (Figure 3) and

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• necessary to give compound 17 in 85% yield after the two steps. Subsequent reaction of the aldehyde 17 following a modified Still–Gennari protocol [29] employing the phosphonate 18 gave the alkene 19 in 90% yield and high selectivity (cis/trans = 25:1). Removal of the silane group with TBAF furnished the

• -unsaturated ester 42. Conversion of the installed alkene to the corresponding thioether followed by the reduction of the ester moiety using DIBAL gave the compound 43, which was subjected to a Stille coupling reaction [38] to yield compound 45. Hydrogenation reaction in the presence of metallic Mg [39

• Wittig reaction led to the α,β-unsaturated ester 87, which was subjected to a hydrogenation reaction in the presence of metallic magnesium, leading to the formation of alkyne 88. The cis-alkene was selectively obtained using the Lindlar catalyst. Finally, hydrolysis of the ester led to the formation of

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

• tris[3,5-bis(trifluoromethyl)phenyl]borane [59], tris(3,4,5-trifluorophenyl)borane [54], and BH3 [55][56] found to be competent catalysts of this transformation (Scheme 3a). The mechanism was proposed to be analogous to that of borane-catalysed alkyne hydroboration; alkene 4 hydroboration, followed by

• , the mechanism was proposed to occur by dehydrocoupling between the aluminium dihydride and the alkyne 1 to give an alkynylaluminium species 78. Direct hydroboration of the alkynyl aluminium species by HBpin gave a gem-aluminyl-boryl-alkene 80 which underwent selective protodemetallation with another

• aluminium-catalysed alkyne hydroboration; hydroalumination of the alkene 4 by the alane catalyst 80, Al‒C/B‒H exchange with HBpin, to give the alkylboronic ester 6 and regenerate the alane catalyst 80. A hydride-mediated decomposition of HBpin and hidden catalysis were not ruled out, as the use of LiH or

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

• single hydroxy group on the central eight-membered ring and 3(11)-epoxyhypoestenone (55) shows a surprising oxa-bridge between the A and C rings, an α,β-unsaturated ketone on ring C, and an endo-alkene into the cyclooctene ring. Recently, Chen et al. reported the synthesis of the tricyclic core structure

• methylene in compound 74 and the formation of a trisubstituted alkene in 75 were assumed to cause an important steric hindrance unfavorable for the cyclization process. As a solution, the RCM was envisaged on 76 which possesses two terminal double bonds and successfully produced cyclooctene 77 in 65–80

• % yield with G-I catalyst in dichloromethane at room temperature. Diene 78 was also designed, with the two alkene side chains closer in length, and the cyclization produced tricyclic 79 in higher yields (80–86%). Finally, diene 80 bearing a functionalized lateral chain was submitted to RCM conditions and

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• benzoyl chloride (26a). The best results were obtained in the reaction of aliphatic enyne 25e with benzoyl chloride (26a) and acetyl chloride (22) in yields of 34% and 65%, respectively. Methyl substitution on the alkene functionality of enyne 25 did not affect the yield, however, methyl substitution at

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• chemoselective and stereospecific mild hydrodesulfurization with Raney nickel in acetic acid affords the target compound 59 as a single Z-diastereomer. Interestingly, glacial acetic acid proved to be the only solvent that could avoid both undesired overreduction and cis–trans isomerization of the alkene bond. It

• during our (formal) total synthesis of (±)-cephalotaxine (130, Scheme 20b) [112]. Here, the desired desulfurization of a 1,4-dithiane could not be achieved without concomitant migration of an alkene double bond (viz 127 → 128), making the final steps to complete the synthesis quite cumbersome, as at best

• mixtures of the desired and undesired positional alkene isomer could be obtained. We believe an outstanding challenge in the field of chemical synthesis is to find mild and catalytic deprotection chemistries for dithiane-type systems, be they reductive, hydrolytic or oxidative. In particular, a more

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• analysis of lactam 19l. In order to shed light on the details of the reaction mechanism, we have performed carefully designed mechanistic studies which consist of experiments on the effect of β-silicon stabilization, the alkene geometry of the α,β-unsaturated acyl chloride reactants, and adventitious water

• group of intermediate 8 is expected to be more nucleophilic than that of intermediate 28 given the fact that allylsilanes possess a significantly higher nucleophilicity than vinylsilanes [69]. Therefore, the electron richness of the nucleophilic alkene appears to be an important parameter in addition to

• and control experiments provided valuable insights on the reaction mechanism including the importance of the β-silicon effect and the alkene geometry of the α,β-unsaturated acyl chloride reactants on reactivity, different potential modes of cyclization, and the effect of adventitious water on the aza

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• -active ester derived from methionine could be converted effectively to α-aminoalkylation product 3al in overall 70% yield, which thus provides a mild method for the functionalization and derivation of abundant natural or unnatural amino acids. Some functional groups such as a terminal alkene in 3am, a

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• ) [30]. HAT reductions of the C9–C11 alkene followed to deliver arisugacin F (35), phenylpyropene C (36), pyripyropene E (38), and phenylpyropene F (41). The steric bulk of the manganese catalyst employed suppressed the undesired reaction with tetrasubstituted alkenes and led to the exclusive reaction

• of the desired trisubstituted alkene due to stabilization of the incipient radical at C9. Furthermore, HAT reduction served to only deliver the thermodynamic product of the trans-decalin. Similarly, the C9–C11 alkene can serve as an ideal handle to C11-hydroxylated products, such as 42, through a

• cyclization (using Bu3SnH and AIBN) [46], led to the construction of the key bicyclo[3.2.1]octene carbocyclic core of jungermatrobrunin, which was further elaborated to 87 in up to 61% yield, after alkene cleavage by OsO4 and NaIO4. The described reductive radical cyclization can be scaled up to 2 g without

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

• the PMB protecting group, Dess–Martin oxidation, and SmI2-induced cyclization. This last step was highly selective, giving solely the intermediate 17. The synthesis was then pursued by the hydroboration–oxidation of the monosubstituted alkene, followed by stereoselective epoxidation of the 1,1

• with a yield of 26%. The secondary alcohol was protected as a MOM ether and the allylic silyl ether was converted to an enone. A selective oxidative cleavage, only affecting the monosubstituted alkene, led to the formation of 31, which underwent a key SmI2-promoted seven-membered ring closure, giving a

• corresponding ketone was achieved using Dess–Martin periodinane with a pyridine buffer. Addition of Me3SiCH2Li efficiently afforded the Peterson adduct 33. The 1,1-disubtituted alkene was then submitted to Mukaiyma hydration to form the tertiary alcohol, in presence of Mn(dpm)3, PhSiH3 and O2. Then, the ketone

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• -stereogenic center, which bears a methyl group, the electrophilic site (the iminium ion), and two possible nucleophilic sites (a prenyl group and a trisubstituted alkene within a cyclohexene ring). In conformer 12a, the prenyl group occupies a pseudo-axial position, the methyl group occupies a pseudo

• -equatorial position, and the trisubstituted alkene within the six-membered ring serves as the nucleophile. It is important to note that in this chair-like conformer, the ethyl ester group at C2 assumes a pseudo-equatorial position. Although an alternative boat-like conformer is also possible (which would

• envisioned for this carbocation (e.g., a nucleophilic attack of formic acid to give a formate ester), only alkene formation was observed in this system. Interestingly, the deprotonation step is completely regioselective, giving the more highly substituted endocyclic trisubstituted alkene found in 8 as

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• involved a highly reactive difluoroethylene intermediate, which was produced by the reaction between halothane and KOH. Keywords: aryl 1-monofluorovinyl ether; electrophilic 1,1-difluoroethene; halothane; multi-halogenated alkene; phenol; Introduction 2-Bromo-2-chloro-1,1,1-trifluoroethane (halothane

• experiments were carried out under argon atmosphere in flame-dried glassware using standard inert techniques for introducing reagents and solvents unless otherwise noted. Typical procedures for synthesis of multi-halogenated alkene Ground KOH (5.0 mmol) was added to a solution of phenol (1.0 mmol) in DME (5.0

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

• -substitution. Subsequent transesterification gave the α-ketoester 75, which was used in a Wittig reaction. The undesired Z-configured double bond was isomerized to the E-alkene and final hydrogenation delivered corynoxine (76). (+)-Gracilamine The Mannich reaction was also used by Nagasawa et al. as a key step

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

• using the UV–vis method (see Supporting Information File 1 for the details) is 5.1, indicating high stability of the anion. Synthesis of dehydroalanine derivatives 6 The reaction products were isolated by column chromatography and analyzed using spectral methods. Both alkene and hydrogenated complexes

• bioactivity [54][55]. To increase the yield of the alkene complexes, the addition of an external “H-abstractor” may be helpful, to suppress disproportionation. A possible candidate may be a reduced radical form of azobenzene. Indeed, the preparative electrolysis performed in the presence of the equimolar

• Ph2N2 additive changed the relative ratio of alkene to hydrogenated derivatives in favor of the former one (see Table 1). As follows from Table 1, the azobenzene additive allows increasing the yield of the alkene complexes up to 85% suppressing formation of the hydrogenated complexes. Spectral NMR

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• for further modification of the triazoloquinoxalines. For example, the alkyne-bearing compound 14f can be used for further CuAAC reactions and compounds including leaving groups, such as in 14j, can be easily converted by nucleophilic substitutions. In addition, compounds with alkene- (14m) or hydroxy

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• . Compound 3a was obtained as a major product (26% yield) and 2a was obtained in 6% yield (Scheme 4a). Hydrogenation of the alkene moiety of 4a would proceed selectively, and 2a would be generated via a transfer hydrogenation reaction from 3a as a hydrogen donor [32][33][34][35]. These results suggest that

• . The reduction of benzophenone also did not proceed smoothly, and only 13% of benzophenone was converted. These results suggest that a Pd/C cathode significantly targets an alkene moiety over a carbonyl group, predominantly leading to the reduction of the C=C moiety. Finally, the electroreduction of 1a

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• medicinal importance is the reason that the synthesis of β-carboline-containing derivatives has been an exciting area for researchers [34][35][36][37][38][39][40]. The Morita–Baylis–Hillman (MBH) reaction is an astonishing C–C bond forming reaction between a carbonyl electrophile and an activated alkene

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

• with the generated styrene in the reaction mixture (Scheme 18) [42]. One year later, the same group investigated the influence of the double bond geometry and the substitution pattern on the alkene. The results indicated that the double bond geometry plays a moderate role, while the bulkiness of the R

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

• model substrate since this alkene had worked well in cycloaddition reactions with various stabilized azomethine ylides [19][20][21][22][23][24]. Initially, we considered the reaction conditions suggested by Grigg and co-workers in the study [27]. An equimolar mixture of 1 and 2a was dissolved in

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• of hydrogen with a pressure of 1 bar, a good selectivity for the hydrogenation of the external alkene is achieved providing enone 27. The reaction mixture containing enone 27 is then mixed with tosylhydrazone and passed through a column with sulfonic acidic resin Amberlyst-15 to catalyze the

• -nonadien-1-al are nearly ubiquitous in modern perfumery for both women and men, even appearing in dark or woody fragrances such as Hugo Boss: Soul. In 2012, Barbaro and co-workers developed a synthesis for alkene 32 by selective hydrogenation of the corresponding alkyne (Scheme 7) [37]. Instead of using a

• . Optimization of process parameters revealed that at a conversion of 75% a good selectivity of 89% for hydrogenation of alkyne 31 to alkene 32 is achieved affording a mixture of (Z)- and (E)-isomers in a ratio of 80:20 [37]. Floral odorants Floral notes, such as rose, jasmine, orange blossom, or lavender, are

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• was replaced by the Zn/Cu couple which was prepared without any metal activation by in situ ball milling of zinc and copper dusts. The advantage of the ball milling process is that the whole procedure is operationally very simplified. The reactive alkene generated was trapped in situ by several dienes

• and was supported by a CH3OD trapping experiment [13]. Thus, DPIBF in this reaction acts both as Diels−Alder trap reagent for reactive alkene [28] as well as radical anion quencher [29][30]. The N,N-Boc-protected N-amidinylpyrrole 28 [31] and 1-guanidinoanthracene (29) [10][32] have functional groups

• (conditions a), imide 44 was the major product accompanied by a small amount of janusene imide derivative 45 (7:1 ratio). The formation of the intermediate alkene 43 was observed spectroscopically only in the milling reaction of 42 alone (an indicative 1H NMR signal of bicyclo[2.2.1] moiety at 5.28 ppm

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• reactions involving the formation of cationic intermediate species [41] like water elimination from an alcohol to provide the corresponding alkene, the isomerization of β-pinene and α-pinene and the cyclization of (S)-citronellal to secondary alcohols. The key point to interpret the action of the capsule in

• subsequent water elimination leading to a stable tertiary, bis-benzyl carbocation that evolves forming the corresponding alkene by proton elimination (Scheme 3). The reaction was carried out at 60 °C with 10 mol % of 16 (Table 2, entry 1), monitoring the formation of the products by 1H NMR and GC–MS (see

• ), with quantitative yield after 20 h at 60 °C in the presence of 10 mol % of the capsule. The same reaction carried out with the capsule 16 and in the presence of 3 as competitive guest led to complete inhibition of the formation of the corresponding alkene (Figure 2D, Table 2, entry 2). This provides

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• achieved with just the rhodium catalyst, by which in contrast, the fully hydrogenated product was obtained. Other series of intermolecular comparative experiments also showed the selectivity of the hydrogenation for the sterically accessible alkene over other sites and even in the presence of inherently

• diterpenoid substrates have four C–C double bonds with a trisubstituted terminal one. Functionalization of these structures would result in mixtures of products derived from each potential alkene group without site-selectivity. The cage host A was proved to recognize organic molecules in water and pre