Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• ). Since this 1,2-shift reaction proceeds under mild conditions and in the absence of a radical initiator, it is thought to proceed by an ionic rather than a radical mechanism. Alkoxy and cyclopropyl radicals, which are more reactive than the usual alkyl radicals, are capable of abstracting hydrogen from

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

• of each strategy, as well as the challenges remaining to be tackled. Keywords: enantioselectivity; grayananes; oxidation; 1,2-shift; total synthesis; Introduction The Ericaceae are a large plant family, with over 4250 known species all around the world [1]. While Ericaceae’s toxicity has been known

• bromide coupling. While both Ding and Luo propose a 1,2-shift relying on epoxide ring-opening as key step, each group proposes a different disconnection. For Ding, the rearrangement forms bond C13–C16 through a Ti(III)-mediated reductive epoxide opening/Dowd–Beckwith rearrangement cascade. This allows to

• have a bicyclo[2.2.2]octane precursor, which can be obtained by a dearomatization/Diels–Alder cascade. For Luo, the 1,2-shift forms bond C12–C13 through a cationic Wagner–Meerwein-type rearrangement. The B ring is obtained by a key bridgehead carbocation trapping, while the skeleton arises from an A

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• features the 1,2-shift of an alkyl or aryl group. In the process, the hydroxy group is converted to a carbonyl and the aldehyde/ketone or imine is converted to an alcohol or amine. Such α-ketol/α-iminol rearrangements are used in a wide variety of synthetic applications including asymmetric synthesis

• ; Introduction When treated with base, acid, heat, or light, many α-hydroxyaldehydes, ketones, or imines 1 undergo a 1,2-shift of one of the α-substituents to the adjacent unsaturated carbon, with a concomitant proton transfer to form compounds of type 2 (Figure 1) [1]. Differing from the related Wagner–Meerwein

• and pinacol/semipinacol rearrangements, the 1,2-shift does not require a leaving group or carbocation intermediate, as the neighboring π system is capable of accepting the migrating group. While the reaction is generally reversible, the product can be favored through four common strategies: (1) the

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• (Figure 1) [28][29][30][31][32]. The calculations were performed using the 6-311G++(d,p) basis set at the B3LYP level of theory [33][34][35][36]. Bis(dimethyl ether)-solvated (1-chloro-2-phenylprop-1-enyl)magnesium chlorides (E)-3e and (Z)-3e were used as model compounds. The 1,2-shift of both the phenyl

• group and methyl group to the carbenoid carbon atom was examined for each geometric isomer to locate the transition state [37]. While appropriate transition state structures were not found for the 1,2-shift of the methyl group in (E)-3e and the 1,2-shift of substituents in magnesium alkylidene carbenoid

• (Z)-3e, transition state structure (E)-3e‡ was found for the 1,2-shift of phenyl group in magnesium alkylidene carbenoid (E)-3e. The geometry around the carbenoid carbon atom in magnesium alkylidene carbenoids (E)-3e (C–Cl: 1.86 Å, C=C–Cl: 115°, C=C–Mg: 135°) significantly deviated from that of the

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• tetrachloride produces an alkyoxy allylic carbocation (not shown). This carbocation is subjected to a regiospecific electrophilic substitution of allene 168 to generate a vinyl cation 172, which is stabilized by an adjacent carbon–silicon bond. The 1,2-shift of the silyl group in 172 produces an isomeric vinyl

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• has a strong proclivity for ring expansion to occur. Accordingly, the 6-membered piperidine ring was enlarged to the 7-membered diazepine ring giving the isolated benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepinium salts 10 via [1,2]-shift. It is noteworthy that the intermediate products 16 bear a

• diazenium function where the electron-deficient N(2) displayed the feature of a latent nitrenium ion. The subsequent [1,2]-shift after cationic Huisgen-type cycloaddition occurs with complete regioselectivity to N(2) not to N(4). Meanwhile, there are two possible migrating moieties: the aromatic side

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• ) via the well-known Trp degradation pathway, the corresponding amino group is found in the ortho-position. An unusual 1,2-shift via the oxirane intermediate 77 was proposed for the formation of the starter unit 78. Using fluorine as a non-reactive anchor on the benzene ring in feeding experiments with

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• diazo esters B involved an isoxazolium N-ylide intermediate C formed by an attack of the rhodium carbenoid onto the isoxazole nitrogen. Furthermore, ylide C could undergo either a 1,2-shift to directly generate oxazine E or a ring opening to 1-oxa-5-azahexa-1,3,5-triene D, followed by a 6π

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• give intermediate vinyl-allenecyclopropane 249, followed by a DVCPR to furnish cycloheptadiene 250. 1,2-Shift and vinyl-carbenoid formation sequences Two major pathways to generate divinylcyclopropanes using transition metal catalysis have been developed. Uemura and coworkers [204] were the first to

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• , anthranilate is converted to 3-aminosalicylate by a multicomponent oxygenase, AntHIJKL [33][34]. The anthraniloyl-S-AntG carboxylic acid-CoA thioester undergoes a never before seen 1,2-shift. Spiteller and colleagues suggested that AntHIJKL promotes this reaction via an epoxide intermediate similar to a

Zinc–gold cooperative catalysis for the direct alkynylation of benzofurans

• Yifan Li and
• Jérôme Waser

Beilstein J. Org. Chem. 2013, 9, 1763–1767, doi:10.3762/bjoc.9.204

• reaction could proceed either via π-activation of the triple bond by the gold catalyst followed by conjugate addition of the benzofuran, α-elimination and 1,2-shift, or oxidative addition of TIPS-EBX (8) onto the gold catalyst (either at the Au(I) or Au(0) oxidation level) followed by electrophilic

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione

• Nargis Sultana and
• Walter M. F. Fabian

Beilstein J. Org. Chem. 2013, 9, 594–601, doi:10.3762/bjoc.9.64

• (TS2), indicating nearly equal bond breaking and formation. The feasibility of the carbanion [1,2]-shift in the benzilic acid rearrangement has been attributed to the special shape [11] of the LUMO of 1,2-dicarbonyl compounds. Path B Product P2 should be even more stable than 2. However, despite

Synthesis of conformationally restricted glutamate and glutamine derivatives from carbonylation of orthopalladated phenylglycine derivatives

• Esteban P. Urriolabeitia,
• Eduardo Laga and
• Carlos Cativiela

Beilstein J. Org. Chem. 2012, 8, 1569–1575, doi:10.3762/bjoc.8.179

• further elimination of a methyl group by 1,2-shift of the Me unit from the N atom to the Pd centre, as previously reported by Heck et al. [20]. As we have shown previously in Scheme 3, in the presence of nucleophiles the process results in the formation of conformationally restricted glutamate derivatives

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• ][6][7][8] illustrate the wide range of applications. As far as sulfonium ylides are concerned, thermally induced isomerisation, that is the 1,2-shift of a substituent (Stevens rearrangement) and [2,3]-sigmatropic rearrangement of allylsulfonium ylides [9][10][11], and the use as C1 building blocks in

Access to pyrrolo-pyridines by gold-catalyzed hydroarylation of pyrroles tethered to terminal alkynes

• Elena Borsini,
• Gianluigi Broggini,
• Andrea Fasana,
• Chiara Baldassarri,
• Angelo M. Manzo and
• Alcide D. Perboni

Beilstein J. Org. Chem. 2011, 7, 1468–1474, doi:10.3762/bjoc.7.170

• intramolecular hydroarylation gave 6-exo-dig or 6-endo-dig processes, depending on the substitution of the alkyne. In both cases, products arising from a direct reaction as well as products involving a 1,2-shift of the amide group were obtained, their ratio being influenced by the polarity of the solvent. The

When gold can do what iodine cannot do: A critical comparison

• Sara Hummel and
• Stefan F. Kirsch

Beilstein J. Org. Chem. 2011, 7, 847–859, doi:10.3762/bjoc.7.97

• cationic intermediates. As outlined in Scheme 16 [90][113], classical cationic intermediates and subsequent loss of a proton do lead to iodine-containing 1,4-cyclohexadienes, the formation of which does not include a 1,2-shift. Additionally, the oxidative power of NIS is able to oxidize cyclohexadienes

Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines

• Paul W. Davies,
• Nicolas Martin and
• Neil Spencer

Beilstein J. Org. Chem. 2011, 7, 839–846, doi:10.3762/bjoc.7.96

• requires fission of three bonds: The propargylic C–N bond in ring expansion; the aryl–aziridinyl C–C bond in the 1,2 shift and the propargylic C–H bond for aromatisation (Scheme 3). The positioning of a deuterium atom at the benzylic carbon in 4 enables the carbons of the aziridine ring to be distinguished

• expansion of metal coordinated alkynyl aziridines to the 5-membered cyclic cation B, which leads to isotopomer G (Path II) and 2,5-disubstituted pyrroles D (Path I), a competing regioisomeric ring-expansion could afford 4-membered ring intermediate I. Evolution of I by a ring-expanding 1,2-shift of the

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• utility of the method can be easily recognized by an examination of the structure of natural products such as repraesentin F, whose core largely comprises the structural motifs generated in this gold-catalyzed cascade. 5 Ring expansions involving enynes The gold-catalyzed heteroatom-assisted 1,2-shift

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• the alkyne by the gold catalyst with subsequent intramolecular nucleophlic attack of the cyclopropene olefin. Ring-opening of the cyclopropyl cation E to generate the 1,3-cyclohexadiene F and a 1,2-shift of the R1 group would then lead to the substituted 4,5-diphenylphenol. In this mechanistic pathway

α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

• David. M. Hodgson and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2010, 6, 978–983, doi:10.3762/bjoc.6.110

• phosphonyl rearrangements (8→9, Scheme 2) were developed by Hammerschmidt and Hanbauer [21], and a stereoretentive N- to C-[1,2]-shift in an α-lithiated pyrrole involving a chiral tert-butyl(phenyl)phosphinyl group has been reported [22]. With regard to previous anion-induced N- to C-1,2-shifts in aziridines

• substrate decomposed under the lithiation conditions. A 2,2-disubstituted N-phosphonate aziridine 1g, available from isobutene and Br2NPO(OEt)2 without UV assistance followed by methanolic NaOMe-induced ring-closure [26][27][30], proved viable in the lithiation [1,2]-shift chemistry giving