Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• . Mechanistic investigation of the intramolecular cyclization The reaction mechanism of the intramolecular cyclization can only be speculative at this stage. We have already reported the generation of a rhodium hydride (Rh–H) complex from RhCl(PPh3)3 and Et2Zn, in which the reaction with tert-butyl acrylate

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

• 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

• reducing agent sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al®), which is a convenient alternative to LiAlH4 that exhibits high solubility in organic solvents and is also known to reduce amides [17]. When a solution of amide 5 in toluene was treated with an excess of Red-Al® at 0 °C, rapid gas

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

• secondary alcohols was prepared and subjected to DIBAL (diisobutylaluminum hydride)-promoted selective debenzylation. Debenzylation proceeded by first removing two dichlorobenzyl groups from the 6A,D positions and then removing one or two benzyl groups from the 3A,D positions. Keywords: aluminum hydrides

• temperature control during the acetolysis step. The silylation method requires careful drying of 1 before the silylation but is otherwise experimentally simple. Hexol 6 was then DCB-protected using 2,4-dichlorobenzyl chloride and sodium hydride in DMSO. As self-condensation of the alkylating agent is possible

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• reaction of o-alkoxythiobenzamides with iodine in the presence of sodium hydride as the base [11]. Sugita et al. reported an unstable iodoalkyne, pentafluoro(iodoethynyl)benzene, which catalyzed the cyclization of thioamides with 2-aminophenol [12]. These approaches have some drawbacks, such as low yields

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• ], MgMS [20], CotB2 [19], and CpCS [21] have been deciphered. All these enzymes undergo a common C1,11–C10,14-bicyclization to form a C15 carbocation, but differ a lot at the following C2,6 cyclization (Scheme 1B). CotB2 and CpCS trigger the C2,6 cyclization via a distant hydride shift, whereas PaFS

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

• under argon. Acetonitrile, dichloromethane, DMSO, DMF and toluene were distilled over calcium hydride under argon. All other reagents were used as received. Chromatographic purifications refer to flash chromatography on silica gel. 1H NMR spectra were measured at 250, 300, 360 or 400 MHz using CDCl3 as

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

• ]. Traditionally, the reduction of nitriles to primary amines relied on stoichiometric hydride reagents [4]. Current catalytic methods for nitrile reduction, hydrogenation [5][6] or hydroboration [7][8], generally rely on metal catalysts, designer ligands, forcing reaction conditions (such as elevated temperatures

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP), to produce mono-, sesqui-, and diterpenes, respectively. The formation of terpenes relies on an assortment of carbocation steps like cyclization, methyl migrations, rearrangements, proton or hydride transfers, hydroxylations, and epoxidations. TPS

• -phase calculations commenced with geranylgeranyl cation (A and A’) in a fully extended form. HP pathway The HP gas-phase pathway commences with a C1–C10 cyclization, which yields cation B, which is more stable than A by −11.4 kcal/mol. A subsequent 1,3-hydride transfer results in an allyl cation (C

• ), which is −18.5 kcal/mol more stable than A. The barrier for the 1,3-hydride transfer is 16.2 kcal/mol for B→C. Subsequently, the double bond on C14–C15 reacts with the cationic charge on C1 to form intermediate D, which is slightly less stable than C (−17.3 kcal/mol) In the enzyme environment

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• ], which was further oxidized to afford 2. On the other hand, the aristolane cyclization route is started from protonation on Δ4,5 of B and followed by 5,10-cyclization to give maaliane-type carbocation intermediate F. Then, a successive transformation involving the concerted 1,2-hydride and 1,2-methyl

• isomerized to nerolidyl diphosphate (NPP), followed by the 6,7-bond formation to generate carbocation intermediate I (Scheme 1, II) [31]. Sequential 1,3-hydride shift and 1,6-cyclization occurred to afford cadinyl cation (J). Further 1,3-hydride shift and deprotonation on J resulted in cadina-1(6),4-diene (L

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• )(phenyl)phosphinate (53) was reduced with lithium aluminum hydride to 2-aminobenzyl(phenyl)phosphine (57). It was oxidized with sulfur to give zwitterionic 2-aminobenzyl(phenyl)dithiophosphinic acid (58), which underwent thermal elimination of hydrogen sulfide to yield 2-phenyl-1,3-dihydrobenzo[d][1,2

• presence of sodium hydride in dioxane, affording tricyclic γ-phosphonolactams 74, 78, and 81 in low to moderate yields (Scheme 14) [34]. In 2005, Aladzheva and co-workers prepared γ-phosphonolactams 85 from the substitution of ethyl 2-(3-chloropropyl)aminoalkanoates 82 derived from glycine and ᴅʟ-alanine

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• moiety in 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), it was well established as a hydride transfer reagent in various organic reactions [14][15]. Generally, DDQ assists in dehydrogenation reactions in organic synthesis [16]. In this context, various carbon–heteroatom bond formation reactions such

• reaction. So, based on literature reports [53][54][55], we have proposed a reaction mechanism in Figure 5b. Initially, DDQ abstracts a hydride ion from substrate 1a to generate the intermediate A. Then intermediate A undergoes an electrophilic intramolecular cyclization to form the cationic intermediate B

• , followed by hydride abstraction to generate the desired product 2a. On the other hand, the formation of quinazolin-4(3H)-ones starts with the formation of an imine intermediate and then it will follow the similar mechanistic pathway. To explore the synthetic utility of the oxidative C–N cross-coupling

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• hydride species 49 that is well known for hydroformylation reactions [77]. Incorporation of the monoligated catalyst into the confined cavity of the capsule showed very good catalytic activity towards the hydroformylation of styrene (50, Figure 11) with a high stereoselectivity (65% ee) at 32% conversion

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• mechanism is shown in Scheme 4. At first, tosylhydrazine as hydride source [29] promotes reduction of 3-phenacylideneoxindole towards 3-phenacylindolinone A. Then, under basic conditions, the carbanion of 3-phenacylindolinone, which acts as Michael donor, is formed. After this the carbanion undergoes

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• ] without observing any product formation with 10 mol % of capsule after 24 h at 60 °C. Similarly, the carvone isomerization [54] involving protonation of the exocyclic double bond of the substrate followed by two hydride shifts and aromatization to carvacrol did not proceed at all with 10 mol % of capsule

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• epoxide guest formed a 2:1 complex, and the internal reactive site of the epoxide was protected by the cyclodextrin host. Therefore, only the terminal site was attacked by the incoming hydride leading to epoxide-ring opening and formation of 1-phenyl-2-propanol (17). Utilizing the similar molecular

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• nine-membered rings 27 via triflic acid (TfOH)-catalyzed reaction of indole-derived phenylenediamine 25 with aldehydes 26 (Scheme 9) [19]. Mechanistically, the initially formed iminium ion I undergoes isomerization to iminium ion II through a 1,3-hydride shift process. Iminium ion III could then be

• generated via 1,6-hydride shift in both I and II. Finally, an intramolecular Mannich-type cyclization then furnishes products 27. The cascade protocol enjoys several advantageous synthetic features, including high step- and atom-economy, transition-metal-free and room temperature conditions. In all cases

• cyclization leading to the formation of polycyclic azepino[5,4,3-cd]indoles. Synthesis of azepino[3,4,5-cd]indoles via iridium-catalyzed asymmetric [4 + 3] cycloaddition of racemic 4-indolyl allylic alcohols with azomethine ylides. Aldimine condensation/1,6-hydride transfer/Mannich-type cyclization cascade of

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• hydride, and C–C bond-forming reductive elimination. Computational results indicate the origin of regioselectivity is involved in the reductive elimination step. Keywords: C–H activation; density functional theory; hydroacylation; iridium catalysis; regioselectivity; Introduction Organic synthesis is

• hydroacylation reactions [74][75][76][77][78], we propose a catalytic cycle utilizing iridium that proceeds with three key steps: (1) iridium(I) oxidative addition into the aldehyde C–H bond, (2) insertion of the olefin into the iridium hydride, and (3) C–C bond-forming reductive elimination. The hydroacylation

• substrate, the active catalyst Ir(COD)OH will undergo oxidative addition into the aldehyde C–H bond. Next, the iridium hydride species will undergo exo-η2-coordination with the olefin of MeOBD to generate intermediates IN1a and IN1b (Figure 1). It is typically assumed exo-η2-coordination is preferential

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• steps as shown in Scheme 3. First, reduction of commercially available indole-2-carboxylate with lithium aluminum hydride in dry tetrahydrofuran gave (1H-indole-2-yl)methanol (10) in 89% yield. The obtained alcohol was exposed to benzoyl chloride and triethylamine to furnish benzoate 11, which was

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• cation (A), followed by direct cyclisation reactions to B and C, a 1,4-hydride shift to D and capture with water to yield 3 (Scheme 1A) [9]. This mechanism was supported by radioactive labelling experiments with [12,13-14C,1-3H]FPP and [12,13-14C,6-3H]FPP, whose enzymatic conversion with PTS into 3

• retainment of labelling was reported for all intermediates until 13, while a loss of tritium was observed for 14 with both substrates. From these experiments it was concluded that the hydrogen H6 must migrate into another position, as realised by the 1,4-hydride shift from C to D. The loss of 3H in the

• neutral intermediates 8 and 6 (Scheme 2C) [13]. In 2010, Faraldos et al. published a third mechanism that also starts with a cyclisation of FPP to A (Scheme 3A) [14]. Similar to Croteau’s mechanism, A is directly further cyclised to H, followed by a 1,3-hydride shift to J (equivalent to the 1,4-hydride

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• we used 2-fluoroaniline (14b), we obtained derivatives 15c and 15d in 60 and 56% yields, respectively, after heating for 40 min (Scheme 4). Then, the derivatives 15a–d were efficiently N-methylated with iodomethane in the presence of sodium hydride, to afford the corresponding methylated 4

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• [56][57][58]. The authors investigated the effect of alkenyl substitution on the reaction to better understand mechanistic details. On inspection of the results, it is clear the radical cyclization pathway precedes the cross-coupling pathway. Moreover, no dehalogenation or β-hydride elimination

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• at reflux temperature in toluene to synthesize the 1,3-oxathiolane lactone 6 via intermediate 5 after elimination of a water molecule. This was further reduced with diisobutylaluminum hydride (DIBAL) in toluene at −78 °C or by lithium tri-tert-butoxyaluminum hydride in THF at 0 °C to obtain lactol 7

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• necessary for this transformation. Recently, copper hydride (CuH) catalysis has been a wonderful procedure for olefin hydrofunctionalization via the formation of nucleophilic alkylcopper intermediate. In 2016, Buchwald and co-workers described a CuH-catalyzed asymmetric addition of olefin to ketones [65

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• attack of an olefinic double bond to the cationic centre Wagner–Meerwein rearrangements, and proton or hydride migrations [2]. These multistep cascade reactions ultimately result in terpene hydrocarbons that are often (poly)cyclic and contain several stereogenic centres [3][4]. In some cases, water is

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• , as a hydride ion source, was conducted to achieve the ionic hydrogenation of intermediate cationic species. However, no products of ionic hydrogenation were obtained, only the product of the hydrophenylation of the acetylene bond 5a was quantitatively isolated (compare with data shown in Scheme 5