Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• the nitrogen atoms adjacent to the carbene center result in kinetic stabilization of the NHC suppressing its dimerization to the corresponding olefin (the Wanzlick equilibrium). On the other hand, thermodynamic stabilization results due to donation of lone pair(s) electrons of the adjacent nitrogen

Organic thermally activated delayed fluorescence material with strained benzoguanidine donor

• Alexander C. Brannan,
• Elvie F. P. Beaumont,
• Nguyen Le Phuoc,
• George F. S. Whitehead,
• Mikko Linnolahti and
• Alexander S. Romanov

Beilstein J. Org. Chem. 2023, 19, 1289–1298, doi:10.3762/bjoc.19.95

• providing ZEONEX® 480 Cyclo Olefin Polymer (COP) used in our studies. We are grateful to Dr. Louise Natrajan at the University of Manchester for providing access to FLS-1000 fluorometer. Funding This work was supported by the Royal Society and the Academy of Finland. A.S.R. acknowledges support from the

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• previously proposed for hypervalent iodine compounds [9][117][118][119], Moriarty proposed a carbene-free mechanism for the formation of 11 [113]. In this, the nucleophilic olefin first attacked the electrophilic iodine center to form zwitterion 15, which closed to produce iodocycle 16 and then underwent

• , they believed that the reaction was likely initiated by either single electron transfer between the reagents (not shown), or by electrophilic addition of the olefin onto the ylide, forming intermediate adduct 17. This was followed by formation of iodocycle 18, from which reductive elimination of

• was also viable with a selection of other mono- and bicyclic olefin motifs, undergoing intramolecular cyclopropanations in moderate to high yields (Scheme 3). They also conducted a mechanistic investigation to better understand this metal-free pathway, again on the premise that a free carbene

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• olefin partners were generally well-tolerated, the protocol was limited to perfluoroalkyl iodides. The reductive power of *PDI•− (*E1/2 = −1.87 V vs SCE) was well-matched to the redox potentials of perfluoroalkyl iodides, but was insufficient for perfluorobromides (e.g., Epred = −1.52 V vs SCE for CF3I

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• radical is stabilized by both the indole ring and the Δ2-olefin. Next, the resonance-stabilized radical intermediate III was trapped by the active α-aminoalkyl radical, generated by reductive decarboxylation by Ir(II) produced in the photocatalytic cycle (which undergoes oxidation to afford the Ir(III

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• the construction of a range of δ-olefin-containing aliphatic nitriles with (E)-configuration selectivity. This new method features wide substrate scope, mild conditions, and direct N–O activation. Keywords: direct N–O activation; E-selectivity; nitrile synthesis; ring-opening cross-coupling; sulfuryl

• ][26][27][28][29], a synthesis method for δ-olefin-containing aliphatic nitriles by the radical C–C bond cleavage of cycloketone oxime ester derivatives was developed by Shi’s group (Scheme 2a) [30], which emerged as an efficient strategy to construct C(sp2)–C(sp3) bonds [31][32][33]. Later, Xiao [34

• translated into experimental reality, developing a new SO2F2-mediated C–C single bond cleavage method for constructing δ-olefin-containing aliphatic nitriles. Results and Discussion We started our investigation by selecting cyclobutanone oxime (1a) and 1,1-diphenylethylene (2a) as model starting materials to

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

• formed after oxidative addition via C–H-bond cleavage followed by olefin insertion to form intermediate 218, which on subsequent reductive elimination results in the formation of monoalkylated bipyridine 219. This intermediate reenters into another cycle of hydroarylation by starting as bidentate complex

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• moderate to good yield (35–82%). 3.5 Ring-closing metathesis Olefin metathesis is a metal-catalysed reaction wherein carbon–carbon double bonds are cleaved and formed through an intermediate cyclometallacarbene 114, thus allowing for transalkylidenation and the formation of mixed alkenes 115 (Scheme 24

• coupling in dibenzo[b,f]oxepine synthesis. Wittig reaction and Ullmann coupling as key steps in dihydrobenz[b,f]oxepine synthesis. Pd-catalysed dibenzo[b,f]azepine synthesis via norbornene azepine intermediate 109. A simple representation of olefin metathesis resulting in transalkylidenation. Ring-closing

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• with good productivity. Alkenes without silicon in the vinyl position seemed much less reactive, such as a vinylacetal, a hindered olefin (3,3-dimethyl-1-butene), or styrene. In these cases, functionalized furfurals were not isolated. In contrast, norbornene, which has a more reactive double bond due

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

• involving these strained bicyclic alkenes are thermodynamically driven forward with the release of ring-strain energy (Figure 1) [7][8]. Intuitively, increasing the number of olefin moieties in the bicyclic system from zero, one, and two, increases the ring-strain energy. Moreover, the introduction of a

• -defined and rigid nature of these bicyclic alkenes creates two diastereotopic faces, namely the endo and exo face (Figure 2). The exo face is sterically less congested than the endo face; therefore, the exo face will typically interact with metal catalysts through side-on coordination of the olefin, and

• into the S–C bond of the thiocyanate 70 to afford intermediate 71 which can side-on coordinate to the exo face of 30b. Subsequently, the thiocyanate attacks the olefin from the endo face via 72 to give complex 73. Reductive elimination furnishes the final difunctionalized product and regenerates the

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

• -olefin 119 which was reduced using DIBAL to lead to the allylic alcohol 120. Subsequent Mitsunobu reaction between the alcohol 120 and carboxylic acid 26 gave the corresponding ester 121 in a 64% yield. However, the intramolecular cyclization step did not lead to the desired compound 122, even when

• to be inactive indicating that the olefin was necessary for cancer cell growth inhibition. For salts 184–187, the authors attributed the decrease in the activity to the lack of phosphatases necessary for the cleavage of the prodrug ester bond and needed to regenerate the drug in the isolated cancer

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

• ][9]. Metathesis reactions take place by the means of a metallic catalyst. Firstly, olefin metathesis was achieved with an air-sensitive tungsten complex [8]. An important focus on air-stable catalyst design was undertaken and contributed to the popularization of the reaction. Thus, Grubbs catalysts

• diastereoselectivity. In a first attempt, the RCM reaction was envisioned prior to the epoxide formation. Unfortunately, no reaction occurred probably due to the presence of the tetrasubstituted olefin. Therefore, this olefin was converted into epoxide 91 and further RCM in the presence of G-II catalyst delivered the

• that a less-hindered olefin facilitated the second enyne metathesis of this tandem reaction. The same strategy was applied for the synthesis of the variecolin [5-8-6-5] skeleton (Scheme 20). Dienynes 112 and 113 were first prepared from methyl ketone 111 and subsecuently submitted to the metathesis

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• room temperature, we obtained the dimeric product (±)-4 in 41% yield. The formation of dihydroxy dimerized RC product (±)-4 was confirmed by NMR spectra. In the 1H NMR spectrum, the olefin proton was observed at δ 6.75 ppm as a singlet, and the two hydroxy protons were observed at δ 5.60 (s, 1H) and

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• this multistep process is initiated by the abstraction of diphosphate to produce an allyl cation that subsequently undergoes typical cation reactions such as cyclisations by intramolecular attack of an olefin to the cationic centre, Wagner–Meerwein rearrangements, hydride or proton shifts. The process

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

• mild conditions, as the acetylene moiety in substrates 25 only reacted to the (E)-olefin while the internal double bond stayed unaffected. Compared to the reaction with benzoyl chloride (26a), which led to the desired dienone 27aa in 55% yield, aliphatic or conjugated acyl chlorides did not affect the

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

• alkylations. Herein, the lithiated sulfur-heterocycles act as a cis-vinyl anion equivalent, a strategy that was developed by Palumbo and co-workers. The method shows some complementarity to the more classical acetylene alkylations, followed by partial hydrogenation to the cis-olefin (see Scheme 10 and Scheme

• reported far less commonly than their use in (4 + 3) cycloadditions [94]. Simple hydrocarbon allyl cations can also undergo (3 + 2) cycloadditions through a purely stepwise cation olefin cyclization-type pathway, but these generally give complex mixtures and low yields and show unpredictable substrate

• suppress homodimerization, via a stepwise (3 + 2) cycloaddition of the initially generated cumyl cation across the olefin in amylene. Our group became intrigued by the potential of dihydrodithiins to act as carbocation-stabilizing groups, as these would represent a synthetic equivalent of ‘naked’ allyl

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

• differences between acyl chlorides 23 and 6 in the examined aza-Nazarov cyclizations can be understood when the electron densities on the two olefin moieties are considered. Indeed, while both of the proposed intermediates 29 and 9 (Scheme 1) can benefit from the β-silicon stabilization effect, the olefinic

• -Nazarov product 7b, albeit in a lower yield (24%). The fact that the other diastereomer of the aza-Nazarov product 7b, which would be formed via the reaction of acyl chloride 6bb with (Z)-olefin configuration, was not observed in this transformation points to a potential E–Z isomerization during the

• reaction. This type of olefin E–Z isomerization is likely to take place after the N-acyliminium formation, possibly via a Michael/retro-Michael addition sequence between the chloride (Cl−) anion and the electron-deficient olefin of the N-acyliminium intermediate at 80 °C (Scheme 9c). In conclusion, these

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

• , olefin, ketone or epoxide functionalities. From a biosynthetic point of view, grayananes arise from an oxidative rearrangement of the ent-kaurane skeleton (Scheme 1). The diversity is generated by cytochromes P450 (CYP) enzymatic oxidation of the grayanane skeleton [17]. The biological activities and low

• -disubstituted olefin and reductive epoxide ring-opening giving triol 18. After oxidation of the primary and the secondary alcohols with Dess–Martin periodinane, the remaining tertiary alcohol was protected as a MOM ether and the silyl ether protecting group was removed. The obtained intermediate 19 was then a

• 2019, Newhouse’s group published a total synthesis of principinol D [26], a compound isolated from Rhododendron principis in 2014 [27][28]. Compared to grayanotoxin III, principinol D displays an inverse configuration at C1 as well as an exo-olefin at C10–C20. The strategy developed by the group relied

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• )-protected ᴅ-serine 12 (Scheme 2). Treatment of the olefin 15 with trifluoroacetic acid (TFA) cleaved the Boc protecting group and the acetonide to deliver unsaturated amino alcohol 16. The amino group in 16 was protected by the fluorenylmethyloxycarbonyl (Fmoc) protecting group for solid-phase peptide

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

• elimination of methanol rather than exocyclic elimination of water, and regioisomeric Rauhut–Currier reaction. Compound 7 was found to be unstable after isolation, possibly due to intermolecular reactions of the electron-poor olefin and furan ring. When a slight excess of 1 was used, only 6n was isolated

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• strategies [27]. Both of these used non-commercially available catalysts prepared over multiple steps, the first an N-heterocyclic olefin [22], and the second a bicyclic (alkyl)(amino)carbine [23]. Both displayed limited tolerance to reducible functionalities. NaHBEt3 is the only known boron-based catalyst

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• alcohols [24], methoxides [23][25][26], carboxylic acids [27], amides [28], ketones [29][30], an exo-olefin [31], and lactones [32]. Elucidating the mechanisms of structural diversification is essential when considering the synthesis of unnatural azoxides by a synthetic biology-based approach. However

• , their enzymatic basis has remained elusive except for the exo-olefin formation in valanimycin biosynthesis, which is mediated by the phosphorylation of a serine moiety by VlmJ and the subsequent dehydration by VlmK [33]. To obtain insights into the late-stage diversification mechanisms, we focused on

• installation of a cis-olefin on the 1,2-positions of the alkyl side chain would afford azodyrecins A–C (1–3), in a reaction likely to be mediated by Ady9, a putative fatty acid desaturase. Nevertheless, the possibility that the desaturation occurs prior to the methyl esterification could not be excluded. The

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• performed at room temperature. As expected, product 3 was formed in moderate yield of 67% as shown in Scheme 7. It is known that difluorocarbene has generally low reactivity towards olefins; however, it can be trapped with electron-rich olefins [32]. In order to trap difluorocarbene with an olefin, we tried

• 1,1-diphenylethylene as a more electron-rich olefin compared to α-methylstyrene was carried out similarly. As expected, the adduct 6 was formed in a high yield of 90% as shown in Scheme 10. Isopropanol can serve as both a proton and a hydrogen radical source while cumene serves only as a hydrogen

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

• ]. Therefore, Roberge, Fogg, and co-workers investigated the advantages of continuously stirred tank reactors (CSTR) and tube reactors in comparison to the corresponding batch reaction for the ring-closing metathesis of diene 58, producing macrocyclic olefin 60 (Scheme 14) [52]. Although, macrocycle 60 is not

• conditions. In contrast, when a continuously stirred tank reactor was used, its head space was continuously flushed with argon to keep the concentration of ethylene in solution as low as possible. In this case, full conversion to macrocyclic olefin 60 (99% yield, detected be GC-FID) could be achieved after

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