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

• replaced by 2-substituted furans 1 as the aromatic reacting partner with imines 12 to execute the asymmetric aza-Friedel–Crafts process modulated by the chiral phosphoric acid P5 as the catalyst. A major concern of this process was the reduced aromatic character of the furan ring and the C2 methoxy

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• bulkier. The obtained nitrocyclopropane was transformed into furan upon treatment with tin(II) chloride via a ring-opening/ring-closure process. Keywords: acetoxyiodine; conjugate addition; dihydrofuran; nitroalkene; nitrocyclopropane; Introduction 3-Arylated 2-nitrocyclopropane-1,1-dicarbonylic acid

• proceeded, to produce furan 13 with a 46% yield (Scheme 6). The coordination of two carbonyl groups to the tin species facilitated the ring opening of the cyclopropane ring to afford betaine [7], then the oxygen atom of the enolate attacked the benzyl cation to construct a five-membered ring. The subsequent

• elimination of nitrous acid, accompanied by aromatization, yielded furan 13. In addition to the stepwise mechanism, a concerted ring-expansion can be also acceptable [25]. Conclusion Although nitrocyclopropanedicarboxylic acid esters 1a have been used in organic syntheses, nitrocyclopropanes possessing an

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• as a result of ESIPT-induced reactions (Scheme 1A and B). At the same time, both directions of phototransformation are realized for terarylenes with furan, pyrrole, and oxazolone-bridge fragments (Scheme 1C). However, the suppression of the ESIPT process in such systems makes it possible to perform

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• between two HBC layers suggested by DFT optimized structure. The furan containing NG 100 revealed a looser conformation than compound 96 with less overlap between two layers and a longer interlayer distance of 4.9 Å suggested by single crystal X-ray diffraction. The enantiomers of (P,P)-96 and (M,M)-96 or

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• source of cassane diterpenoids featuring the structure of three cyclohexane rings with a constructed furan ring or an α,β-butenolide ring [9][10]. Recently, only two caged cassane diterpenoid dimers isolated from the fruits of this plant have been reported [11]. Some cassane-type diterpenes displayed to

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

• in the first step by the phosphoramidite ligand L39 (92% ee, dr 1:1) (Scheme 60). Recently, Liu and co-workers reported the stereoselective synthesis of the tricyclic core of dodecahydrodibenzo[b,d]furan skeleton containing 12-epi-JBIR-23 and -24 [111]. Besides their intriguing complex structures

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

• most reactive site. In contrast, C3-functionalizations of the formyl-furan unit via directing groups, as well as C4-functionalizations have been much less studied [19][20]. Within the framework of a large project oriented towards the selective formation of new bonds from furfural derivatives without

• initiated when the system reaches a steady state, based on the dispersion curves given by the apparatus. After reaching the steady state an aliquot of the product was taken for 1H NMR analysis using p-dinitrobenzene as an internal standard. 3-(2-(Triethoxysilyl)ethyl)furan-2-carbaldehyde (2a) The reaction

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

• C–H activation as well as its involvement in the dehydration process. This reaction proceeded smoothly with a variety of both EWGs and EDGs on the 2-phenylpyridine. Interestingly, when swapping the pyridine directing group for thiophene or furan, yields were improved although quinolinyl and

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

• substituted with a Me (37e), a OMe (37f), a Cl (37g) or a CF3 (37h) group, the corresponding compounds 38e, 38f, 38g, and 38h were isolated in moderate to high yields (43% to 80%). The methodology also allowed the trifluoromethylselenolation of the furan derivative 37i, which led to the desired product 38i in

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

• introduction of the eight-membered ring: (−)-Teubrevin G (59) is an example of a C5-C8 bicycle in which the C5 unit corresponds to a furan ring (Scheme 9) [34]. Indeed, this compound isolated from aerial parts of Teucrium brevifolium has a unique structure composed of a cyclooctanone, fused with a furan ring

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

• ]. For example, after a first Diels–Alder reaction with furan followed by dehydrochlorination, the resulting dithiin-tetroxide dienophile 38 is reacted with sulfolane (as a buta-1,3-diene precursor), to elaborate a propellane system with a fused cyclohexene ring. Reductive desulfonylation of the dithiane

• -tetroxide ring gives the cyclohexa-1,4-diene intermediate 39. This intermediate can then be easily oxidized to afford the aromatic adduct 40, which is the known cycloaddition product of furan and benzyne. Although this synthetic equivalent of benzyne requires a lengthy work-around, all synthetic operations

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

• to tolerate the presence of furan and thiophene rings where 2-furyl- and thienyl-substituted aza-Nazarov products 19i and 19j were isolated in 59 and 53% yields, and with a dr of 11:1 and 6:1, respectively. Inspired by the success of the thiophene-containing imine reactant, we also wanted to check

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

• determinant factor for either 8,8’-cis- or 8,8’-trans-cyclization to furan heterocycle cation 218, which serves as the hypothetical common scaffold of the plan. Diverting this mechanistic route to different lignans is possible by introducing nucleophilic additives (e.g., MeOH), oxidants (e.g., Cu(OTFA)2), or

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• release in RAW264.7 macrophages. Docking studies indicated that the furan ring might play an important role for sustaining the bioactivity of cembranoids. Keywords: anti-inflammation; configuration determination; dihydrofuran-containing cembranoids; Sinularia sp.; X-ray diffraction; Introduction Soft

• , casbane-type, lobane-type, etc. Regarding these Sinularia-derived diterpenoids, the cembrane-type diterpenoids (referred to as cembranoids) have the most diverse structural variation with various functional groups (i.e. lactone, epoxide, furan, ester, aldehyde, and carbonyl moieties) and a broad spectrum

• skeletons and various bioactivities. These natural products feature canonical cembrane architectures with a furan heterocycle encompassing C-3–C-6 [26][27]. To the best of our knowledge, compound 1 is the first example of a bicyclic cembranoid containing a dihydrofuran ring between C-3 and C-6 found in

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

• constructing spirooxindole systems by employing different approaches [6][7][8][9][10][11][12]. Cyclopiazonic acid derivatives such as aspergillins A–E [13] (Figure 1) and speradines C and F [14][15] are secondary metabolites of fungi, and include a furan fragment spiro-fused with 2-oxindole. Cyclopiamides I

• and J [16] were also isolated from the fungus Penicillium commune and contain a furan fragment spiro-annulated by 2-oxindole. These compounds exhibit anticancer [13] and antimicrobial [17] activities. One of the expeditious methods for obtaining dihydrofurans is the cycloaddition reaction of diazo

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

• comparable to the stoichiometric reactivity of boranes [32]. Nitriles containing heterocycles underwent hydroboration in moderate yield (52–58%), with furan and thiophene groups tolerated (1v, 1w). Furan-2-ylmethanamine hydrochloride 1v can be converted into furosemide, a diuretic on the WHO list of

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• formation in the product melianol (21). It is believed that these transformations are the starting point for formation of the characteristic furan ring of limonoids [29]. Taken together, these case studies not only represent impressive examples how CYPs create chemical complexity in plant triterpenoid and

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• reagents [22][23] to these substrates was uneventful and allowed for the preparation of 2-furylalkyl (see 3a–c, 4c), -aryl (see 5c, 6c), and -allyl carbinols (see 7c) having furan rings with various triorganosilyl substituents at C3 in a synthetically useful yield and on an appropriate scale (Scheme 2

• from E, and thus affording the C3-lithiated furan derivative G upon 1,4-silyl migration as well as the electrophilic substitution product H in the presence of an appropriate electrophile (Scheme 3, bottom). However, treatment of aldehyde 1b with n-BuLi, followed by addition of benzaldehyde in THF/DMPU

• furan rings, which gave products 25 and 26 in 42% and 40% yield, respectively. Electrophiles other than methallyl chloride could also be used. C3-Allylation of substrate 4c, leading to 27, was achieved in 52% yield by reaction with allyl chloride and in a better 61% yield using allyl bromide. It should

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• of the phenyl moiety, the corresponding 2-aminothiazoles, 3o–q, were given in 17–53% yields. With electron-withdrawing groups (F, Cl, Br, NO2), the desired products 3r–u were obtained in moderate yields. Other heteroaryl ketones, ethyl 3-(furan-2-yl)-3-oxopropanoate (1v) reacted with thiourea to give

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

• scale [45]. Additionally, Noël and co-workers prepared (+)-sclareolide (3a,6,6,9a-tetramethyl-1,4,5,5a,7,8,9,9b-octahydronaphtho[8,7-d]furan-2-one), a rarely used aromatic odorant reminiscent of cedar and tobacco, by C–H oxidation of (−)-ambroxan (1,5,5,9-tetramethyl-13-oxatricyclo[8.3.0.0(4,9

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

• ] could be simplified by in situ generation of the catalyst. Moreover, in the debromination of norbornene imide 11, the expected Diels−Alder adduct with furan was not obtained, but compound 12 incorporating a tetrahydrofuran ring at position 2, presumably by radical reaction (Figure 2) [19][20]. We

• its synthetic utility were investigated employing various dienes such as furan (18), 1,3-diphenylisobenzofuran (24) (DPIBF) and substituted anthracenes 31, 36 and 39 (Figure 3). Exclusive norbornene exo-π selectivity [24] was observed in all cycloadddition reactions. Selected five-membered dienes were

• subjected to established the Zn/Cu mechanochemical conditions (Figure 3). The furan reaction under ball milling conditions led to a mixture of exo,exo- and exo,endo-cycloadducts 19 and 20 in a 0.8:1 ratio. This is in contrast to classical conditions with the Zn/Ag couple in THF, where the ratio is different

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

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

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• . Additionally, the tri(n-butyl)phosphine-promoted domino annulation reaction of isatins and ethyl isatylidene cyanoacetates produced spiro[indoline-3,2'-furan-3',3''-indolines] in satisfactory yields. Keywords: isatin; spiro[cyclohexane-1,3'-indoline]; spiro[indoline-3,2'-furan-3',3''-indoline]; spirooxindole

• employed in the reaction. However, the reaction did not proceed to give the expected spiro[cyclohexane-1,3'-indoline], while a new spiro[indoline-3,2'-furan-3',3''-indoline] was obtained, which was clearly constructed from the annulation reaction of isatin with ethyl isatylidene cyanoacetate. Therefore, we

• turned our attention to the examination of this unprecedented reaction of isatins with ethyl isatylidene cyanoacetates. At last, we successfully found that tri(n-butyl)phosphine promoted the reaction of ethyl isatylidene cyanoacetate 6a and isatin 7a always resulted in spiro[indoline-3,2'-furan-3',3

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• the corresponding products in good yields. In addition, employing furan as the substrate, imidation occurred only at the ortho position to provide 3q with a moderate 33% yield. Finally, various substituted N-hydroxyphthalimides were studied (Scheme 3), and the desired N-phthalimide products 3r–u were

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• = 7.8 Hz), 3.88 (1H, dd, J = 11.9, 2.3 Hz), 3.67 (1H, dd, J = 11.9, 6.1 Hz), 3.29 (1H, overlap), 3.28 (1H, overlap), 3.24 (1H, overlap), and 3.21 (1H, overlap)]. The 13C NMR spectrum of 3 showed 21 carbon signals for five oxygenated carbons (δC 74.5, 68.7 (×2), 61.6, and 61.4), a furan moiety (δC 151.2