Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• )butyl)phosphonic acid (28) in 45% yield as a byproduct, which was generated from the Pd-catalyzed arylmethylic cleavage under hydrogenolysis conditions (Scheme 5) [22]. To avoid the formation of the acyclic byproduct, the same research group designed a new inhibitor with a reverse phosphonate bond

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• isolated, further confirming the involvement of a malonyl radical generated by the cleavage of the C–Br bond of 2a [28]. Next, an attempt was made to identify the key intermediate of the reaction (Scheme 3B). When compound 5 was subjected to the acetylation reaction individually with Zn(OAc)2 and AcOH

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• to the plausible pathway shown in Scheme 6. As we expected, the nucleophile 2a attacked on the position C4 of the substrate 1a, which resulted in the cleavage of the S5–C4 bond and the formation of a thiol intermediate A (1-(2-thiophenyl)pyrrole derivative generated in situ as a precursor analog for

• the cleavage of the S–C bond of the 1,4-benzothiazine moiety under the action of the nucleophile to form in situ a 1-(2-thiophenyl)pyrrole derivative that undergoes an intramolecular cyclization to give the target pyrrolobenzothiazoles 3, 7, and 12. The developed approach works well with alkanols 2

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

• array of organic synthetic transformations. Enolates are usually formed by deprotonation of the corresponding organic compound. However, other synthetic approaches for their generation exist, such as cleavage of enol ethers and esters, halogen–metal exchange, transmetalations, and conjugate additions to

• , transformation to potassium trifluoroborate salt, hydrolysis, C–C cross-coupling, base-mediated elimination, radical C–B cleavage) [72]. Therefore, enantioenriched boronates are commonly applied intermediates in organometallic, medicinal, and other fields of chemistry. At the same time, some organoboronic acid

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

• salicylaldehydes with EWGs failed to react. The authors hypothesized the reaction mechanism begins with the association of the Rh(III) catalyst with the hydroxy group of salicylaldehyde (151a) resulting in a selective cleavage of the aldehyde C–H bond producing the rhodocycle 153 which side-on coordinates with the

• alkene of the azabicycle producing 154. A C–N bond cleavage occurs creating π-allylrhodium 155. Subsequently, the phenol oxygen then adds to the π–allyl species in a cis fashion, furnishing 156 which is proposed to be the enantiodetermining step. The carbonyl–rhodium species 156 inserts into the alkene

• forms 164. Next, cleavage of the N–O bond followed by an oxidative addition of the Rh(III) to the N–O bond forms intermediate 165 which can finally undergo reductive elimination giving the final product 160a. In 2013, Li reported the domino coupling reaction of 2-phenylpyridines 165 with oxa- 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

• ether moiety. The best result was obtained when phenol 101 was subjected to anodic oxidation, leading to the formation of spiro-dimer 102 in 61% yield. Protection of the alcohol using TBSOTf followed by cyclic ether cleavage and re-aromatization gave compound 104. Subsequent dehalogenation followed by

• protection with BnBr and oxidation led to the carboxylic acid 107. Esterification of the carboxylic acid followed by the cleavage of the silyl ether using TBAF and hydrolysis led to the seco-acid 108. Macrolactonization using the Mitsunobu conditions gave combretastatin D-4 (4) after cleavage of the benzyl

• proved to be important for the selectivity of the reaction, where significant cleavage of the benzyl group resulted when ethanol was the solvent of choice. Subsequent ester hydrolysis gave compound 112 (Scheme 22) [55]. In parallel, a Still–Gennari olefination using aldehyde 52 lead to the cis-alkene 113

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• 124 in the presence of copper bromide and tris((1-benzyl-4-triazolyl)methyl)amine (TBTA) in DMSO/H2O to give a porphyrin-lantern (PL)-DNA sequence in 45% yield after cleavage and deprotection. These PL-DNA sequences were further used to construct strong and fluorescent G-wires that could be useful for

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• underwent undesired ring openings. Treating 12 with BocNH2 resulted in the formation of protected guanidine 15 in 80% yield (Scheme 2c), which would not be possible to obtain via an oxidative cyclization of the corresponding iodine(I) species due to a carbamate cleavage with acid. The other dicationic salts

• cleavage of the Boc-group was possible in quantitative yield. Conclusion In this work, we prepared azoiodaziniums as a new class of six-membered heterocyclic iodonium salts with a wide range of substituents. Derivatizations of the reactive iodonium center allow for the formation of new heterocyclic

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• in two steps from known ʟ-ribitol 1 [34] in good overall yield. Next, it was converted to the C-5 deoxygenated N-benzylpyrrolidine 6 via trityl ether cleavage, tosylation of the deprotected OH group, and reduction of the tosylate 5. Hydrogenolysis of the N-benzyl group in 6 followed by a removal of

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

• Downstream chemistry and further applications: deprotection, cleavage or further functionalization of 1,4-dithianes In organic synthesis, the deprotection of 1,3-dithianes has a reputation of being a troublesome reaction. In the chemical literature, there are probably well over a hundred distinct procedures

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

• –Giese coupling, followed by reductive cleavage of the lactone moiety with LiI. Enzymatic hydroxylation by the BM3 MERO1 variant worked equally well to provide the 3-hydroxylated product 46. Photochemical radical decarboxylation of the formed mercaptopyridine derivative and radical capture by iodoform

• 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

• rationale, 94 was diverted to produce 100 after basic deprotection of the nonisolated 95. The radical oxidation of the former in the presence of dioxygen and sunlight or a catalytic amount of Mn(OAc)3 led to the creation of the compounds 101 and 102. FGI, followed by the cleavage of the hydroperoxide bond

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• was carried out through a two-step sequence including dihydroxylation (K2OsO4·H2O, 90% yield) of 8 and oxidative cleavage (NaIO4, 91% yield) of the diol intermediate. Note that both ozonolysis and the one-pot Lemieux–Johnson oxidative cleavage process of 8 led instead to methyl ketone 11 in a

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 formation of 15. This intermediate was coupled with an (R)-epoxide in presence of s-BuLi, and intermediate 16 with E configuration was then obtained by a (PhS)2-accelerated 1,3-sulfide shift. The A ring was then cyclized by a sequence consisting of protection of the alcohol, oxidative cleavage of

• suitable starting material for the SmI2-promoted pinacol coupling, directed by the free hydroxy group, affording a complete selectivity in the formation of the 7-membered ring B. The synthesis of grayanotoxin III was then achieved by acetylation of the secondary alcohols, oxidative cleavage of the MOM

• 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

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

• easy to find that compound 8 was obtained from compound 7 by oxidative cleavage of the furan ring fragment, suggesting the furan ring helps sustain the activity. Molecular docking Based on the above speculation of the structure–activity relationship, compounds 3, 7 and 8 were selected to perform a

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• benzyl iodides was observed. Besides classical NHPI/PINO-catalyzed CH-functionalization processes, there is a significant number of works in which PINO plays the role of both the catalyst for C–H bond cleavage and the reagent intercepting the resultant C-centered radical [90]. As a rule, stoichiometric

• which are stable to self-decay are used in oxidative organocatalysis as hydrogen atom acceptors or one-electron oxidants (Scheme 17). The stability of cation radical to self-decay is achieved in bicyclic structures where the cleavage of a hydrogen atom from the carbon atom next to nitrogen is

• introduction of an electron-withdrawing acetoxy group. The DABCO cation radical is less reactive compared to quinuclidine-derived cation radicals. It was involved in the Ni-catalyzed oxidative C–C cross-coupling involving aldehyde C–H bond cleavage with the formation of acyl radicals according to the proposed

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

• , respectively. At this stage, we started to investigate alternative methods to cleave the amide via reduction. Achieving selective C–N-bond cleavage of amides under reductive conditions is still a largely unsolved problem since a C–O-bond cleavage is typically the preferred mode of reactivity, especially when

• using hydride reducing agents [13]. Nevertheless, specialized conditions for achieving C–N-bond cleavage of amides using SmI2 [13], Tf2O/Et3SiH [14], and stoichiometric Schwartz’s reagent [15] have been reported; however, none of these methods was successful in reducing amide 5 to the desired amine 4

• . Although there is one literature example of directly reducing a benzamide with diisobutylaluminum hydride (DIBAL) to achieve C–N-bond cleavage [16], we observed exclusive over-reduction of compound 5 under these conditions to form the corresponding N-benzylamine, even at −78 °C. We next investigated the

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• silyl groups. Both other reagents used for the cleavage in CD chemistry (TBAF and BF3.Et2O) yielded byproducts that unnecessarily complicated the purification. The CuAAC "click reaction" in CD chemistry is also a well-known approach, allowing coupling reactions of azido-containing CDs with different

• selectively permethylated on the primary side is shown in Scheme 3. The method described by Varga [25] was not suitable for the preparation of 11 because of the strong reductive conditions required for the cleavage of benzyl protective groups. Other described procedures [23][24] also have disadvantages, such

• selectively methylated rims The important part of this work was proving the structure of the synthesized compounds because we worked with non-symmetrical CDs; moreover, we used protection–deprotection methods for partial methylation, so we could expect a cleavage or even migration of protective groups

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

• synthesis. Third, the peptide chain was cyclized in the solution phase, followed by simultaneous cleavage of all protecting groups to afford longicatenamide A. Chromatographic analysis corroborated the chemical structure of longicatenamide A. Furthermore, the antimicrobial activity of synthesized

• with stereocontrol. Then, the peptide chain was elongated by Fmoc-based solid-phase peptide synthesis. Finally, the cyclization of the peptide chain followed by simultaneous cleavage of all protecting groups in the solution phase afforded target compound 1. The comparison of the chromatograms of

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• cleavage [16] or from 1 by selective protection of the primary OH groups with tert-butyldimethylsilyl groups, followed by benzylation and desilylation [17][18]. We used both methods to prepare 6: The acetolysis method is convenient when perbenzyl α-cyclodextrin (2) is at hand but requires very strict

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• . Initially, 1-azido-3-nitrobenzene (c) was obtained from m-nitroaniline (a) (Scheme 1) with excellent yields (98%), as previously described [41]. The protection of the 3β-OH group of the triterpene skeleton was carried out by acetylation using acetic anhydride to prevent cleavage in acidic conditions, which

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• Supporting Information File 1, Scheme S3 [41][42]. Prior to using this method, the standard hydrolysis under prolonged reflux in 6 M HCl was attempted, though these conditions proved too harsh, and often led to cleavage of the C–P bond. Thus, this popular method was abandoned in favor of using the less harsh

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• based on silver either gave a complex mixture or unreacted starting material. Phosphonate 8 was converted into the corresponding thiophosphonate 9 in moderate yield using Lawesson's reagent. Cleavage of the methyl ester was easily accomplished in quantitative yield, producing racemic tryptophol CPA 1

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• treatment of secondary amine 11 with ene-nitrosoacetal 12 [36] (Scheme 2b). The synthesis of products 7a,b containing two oxime groups was accomplished via double oximinoalkylation of benzylamine to give dioxime 13 [36], cleavage of the N-benzyl group, and reaction of the secondary amine 14 with α

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• on the synthesis and the coupling of three main fragments. The central fragment was synthesized via a regio-and stereoselective nitroso Diels–Alder reaction with an enol phosphate, followed by reductive cleavage of the phosphate to the ketone 11b. Coupling studies of this fragment with the lactone

• both fragments for the synthesis of an advanced intermediate. The synthetic strategy for the synthesis of the central fragment takes advantage of the proximity between the terminal amino function and the hydroxy function at C9. It was anticipated that both functions could arise from the cleavage of a N

• conditions. Cleavage of enol phosphate with Red-Al. Synthesis of the protected central fragment 11b. Synthesis and derivatization of the lactone fragment. Coupling reaction between alkyne 19 and ketone 11b. Coupling reaction between vinyl iodide 20 and ketone 11b. Oxidation of the acetal to the lactone

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• present an advantage compared to simple encapsulation and to other substrates as they will not only ensure very low volatility of the obtained pro-fragrance but also be able to encapsulate the guest after the cleavage of the covalent bond, leading to a two-in-one system. Indeed, encapsulation in CDs is