Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• deprotection of the cyclization precursor was essential, as the TES-protected analogue of 35 failed to deliver the desired spirocycle 38 under the Nazarov cyclization conditions. α-Oxidation of 38 with molecular oxygen afforded 39, which was then converted to 40 via formation of a chloromethyl silyl ether

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• congested benzofuranone-based 4,5-spirocycle [26]. Starting from Wieland–Miescher ketone (18, Scheme 4), the synthesis proceeded through a sequence of transformations: the nonconjugated carbonyl was chemoselectively protected as ketal 19; the unprotected ketone then underwent α-methylation to provide 20

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• obtained axial chirality is identical to the naturally occurring one. Almost at the same time, Soorukram and co-workers reported the same approach to access the dibenzocyclooctene member gymnothelignan V [41]. Next, we examined the bioinspired transformation of the linear skeleton to the spirocycle. By

• cyclization to forge the spirocycle in one step represents a comparably more powerful method to rapidly generate complexity, since the de novo synthesis approach by Cuny and co-workers [42] has inevitably met with a lot of problems on stereoselectivity although they started the synthesis from a tricyclic

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• condensation, cyclisation, and cycloaddition as an efficient strategy for the rapid formation of complex spirocyclic products that could have value for the formation of novel, bioactive oxindoles. Keywords: cascade; cycloaddition; oxindole; spirocycle; stereochemistry; Introduction The Alstonia alkaloids are

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• successful as the reaction was stopped at the spirocycle 4d formation stage (Table 1, entry 9). The removal of the N-Alloc group in unsaturated ester S-3d was performed using a Pd catalyst and pyrrolidine as a nucleophile. The use of Pd(PPh3)4 as the catalyst led to a fast consumption of the starting

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• moderate to good yields of the spirocycle. The reaction is assumed to proceed through a Michael addition followed by Williamson etherification of the resulting γ-hydroxyselenone 12. In 2022, Kleij et al. reported a domino synthesis of bicyclic 3,5-anhydrofuranoses 15 using easily accessible bis-epoxy

• acids under blue-light irradiation, and the Giese adducts were obtained in moderate to high yields. As demonstrated by the authors, this protocol is also suitable for synthesising oxetane-containing dipeptides, and opens the door for exploring a novel oxetane-spirocycle motif if the γ-aminoester product

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• illustrate that a spirocycle can alter the stability, physicochemical, and pharmacokinetic properties of the structure [9]. In this review, we summarize recent synthetic procedures reported between 2000 and 2023 for synthesizing steroidal spiro heterocycles. The review categorizes the procedures based on the

• (Scheme 16). Remarkably, the hydroxy group at 50a remained unprotected. Additionally, the isomers of 52b,c were cleanly separated on neutral alumina. In the case of the estrone derivative, the spirocycle was built at C-17 in only 30% yield, not being the main product, but a rearranged deoxygenated

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• presented in Scheme 5. As can be seen, the yields of the target compounds 4 vary from good to moderate per two steps of synthesis. The introduction of acceptor substituents in both the aniline and arylidene moieties of the DAS molecule leads to a decrease in the yield of the final spirocycle. The structure

• from each of the bromo-substituted alcohols used by us have two main pathways of transformation under the action of base: 1) exo-tet cyclization with substitution of the bromine atom and formation of the spirocycle, and 2) migration of the exocyclic double C=C bond into the imide cycle (the process is

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• aromatic ring, forming intermediate 41, which was then oxidized to cation 42, thereby completing the photocatalytic cycle. The reaction proceeded by regioselective nucleophilic addition of H2O, accompanied by the loss of MeOH to deliver spirocycle 43. Notably, the dearomative spirocyclization of biaryl

• quenching is not thermodynamically favorable, the single electron reduction of RAEs can proceed via an alternative mechanism. For example, in the transformation of NHPI ester 44 into spirocycle 45 catalyzed by [Ir(ppy)2(dtbbpy)][PF]6, Reiser and co-workers observed that the excited state of this Ir-catalyst

• , whereas the corresponding spirocycle in kadsulignan E was formed under Ir photocatalysis. In addition, photoinduced Pd catalysis was applied in the key macrocyclization

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

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• , followed by a favoured 6-endo-trig cyclisation driven by the 4-methoxy group to form the 6,6-spirocycle 11. The addition of water and subsequent ring-opening would then form the acid 12, which upon elimination of water would then provide the observed acid chloride 13. We wished to also determine whether

• form the 6,6-spirocycle 19. A 1,2-rearrangement would then produce the observed product 17. Presumably the analogous dichloroalkenone 6d does not undergo this cyclisation due to the deactivation of the ring by the ketone towards nucleophilic attack. Conclusion In conclusion, we have shown that 1,1,1

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• enyne substrates, the one-pot reaction manifold enabled the anchorage of non-steroidal spirocyclic moieties at C-17. The procedure proved efficient and stereoselective with mestranol and lynestrenol derivatives incorporating a 2-tetrahydrofuranyl spirocycle at C-17. It was more difficult with 2-oxepanyl

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• compounds gave 17 in 59% yield and the spirocycle 12 in 8% yield. In the case of the dimethyl allyl analogue 22, reversible protonation (HCO3−) of the enamine moiety in 27 (Scheme 7) and subsequent intramolecular cyclisation would realise the bridged heterocycle 22, with this latter reaction promoted by the

• gem-dimethyl effect. In the case of the spiro products, an exception is the spirocycle 23 derived from cinnamyl bromide reaction with the intermediate 29 (see Scheme 8). At the O-cinnamyl stage, the formation of two highly stabilised radicals could provide a driving force for a 1,3-shift leading to

Development of an additive-controlled, SmI₂-mediated stereoselective sequence: Telescoped spirocyclisation, lactone reduction and Peterson elimination

• Brice Sautier,
• Karl D. Collins and
• David J. Procter

Beilstein J. Org. Chem. 2013, 9, 1443–1447, doi:10.3762/bjoc.9.163

• side chain gave the expected spirocycle 2f, albeit with low conversion (unoptimized). As expected, no products arising from the reduction of the ester were observed [40][41][42]. Telescoped spirocyclisation/lactone reduction Although the reduction of the spirocycles 2 proceeds smoothly with SmI2−H2O

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• enol ether function, followed by 6-exo-trig cyclization, completes this sequence of events and provides the dioxane derivative 46. Interestingly, no reaction was observed when the spirocycle 41 and the dioxanes 35, 36 and 39 were reacted under acidic conditions, indicating that the final step is not

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• -component coupling reaction (Scheme 8). As described in our previous communication [61], the employment of bifunctional catalyst 9 [54][55] in a highly stereoselective two-stage one-pot cascade led to the formation of enantiomerically highly enriched spirocycle (+)-1a (Scheme 8). In a repeat of the process

A thermally-induced, tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition approach to carbocyclic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2010, 6, No. 33, doi:10.3762/bjoc.6.33

• ]. Spirotryprostatin B (2) is just one example of many natural products from this class exhibiting interesting biological activity [2]. Compounds possessing a carbocycle at the C3 position of the oxindole, such as 3, are less common and spirooxindoles containing a four carbon spirocycle are rare. One notable natural

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• example) [39]. Even greater reactivity towards intramolecular nucleophilic attack is exhibited by isonicotinamides when activated by N-sulfonation [40][41]. For example, the N-furylmethyl isonicotinamide 3 cyclises to the doubly dearomatised bis-spirocycle 4 on treatment with triflic anhydride in the

Allylsilanes in the synthesis of three to seven membered rings: the silylcuprate strategy

• Asunción Barbero,
• Francisco J. Pulido and
• M. Carmen Sañudo

Beilstein J. Org. Chem. 2007, 3, No. 16, doi:10.1186/1860-5397-3-16

• , react with CH2I2/Me3 Al at low temperature (-60°C to room temperature, then 48 h at r.t.) giving spiro-cyclopropanes 35–39 containing the spiro[2][4]heptanol moiety (Scheme 7). [20] High levels of stereoselectivity were found in all the examples studied. Formation of the spirocycle proceeds by a two