Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• prepared the (−)-adaline (1) and the non-natural isomer (−)-euphococcinine (2) through a four-step intramolecular Mannich cyclization cascade reaction [57]. In this methodology, the alkaloids were prepared by treating the convenient N-sulfinylamino ketone ketal precursor on heating with NH4OAc:HOAc. Oxo

• %, respectively. The conversion of precursors N-sulfinylamino ketone ketals directly to the desired homotropanes represents a four-step intramolecular Mannich cyclization cascade reaction, being the most efficient method to date for the (−)-adaline (1) and (−)-euphococcinine (2) syntheses. Specific rotation was

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• radical precursors in this system, allowing for both alkyl [44] and acyl [45] RCA reactions. In the case of acyl DHPs, they propose that direct excitation of the DHP leads to radical generation rather than the iminium intermediate (Scheme 9c). The same system was used for the radical cascade reaction

• separately developed a Minisci-type reaction using phthalimide esters 123; however, their system did not extend past isoquinoline substrates 124 (Scheme 17b) [62]. Zheng and Studer expanded the scope of this type of reactivity to a three-component cascade reaction with alkyl bromides 125 and enamides 126

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• : phosphonium salt-catalysed triazolation of MBH adducts. Scope of the one-pot cascade reaction of the unprotected Morita–Baylis–Hillman adducts 3a–q. Comparative analysis of the sequential one-pot reaction. Optimization of the triazolation of the MBH adduct 1a. Optimization of the reaction conditions for 3

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• pleased to report here that this cascade reaction takes place efficiently, resulting in the regio- and stereoselective formation of the poly-substituted isoquinolinones 4 in good to high yield. Applications of this reaction can be relevant for improvements of structure diversity and fine tuning of the

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• Pd-catalyzed cascade reaction (C–C bond formation/C–H cyclization process) of N-arylpropynamide 4 for the preparation of indolinone derivatives 5 was previously reported by Li’s group [34][35]. In another report on C–H cyclization by Lei’s group, Ni-catalyzed aromatic C–H alkylation occurs via a

Terpenes

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 2966–2967, doi:10.3762/bjoc.15.292

• generate a highly reactive cationic intermediate that can be subject to a cascade reaction through typical carbocation chemistry, including cyclisation reactions, hydride migrations and Wagner–Meerwein rearrangements [1][2]. The cascade is usually terminated by deprotonation or attack of water. The

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• together with 1.5 equivalents of 3a led to a higher conversion (ca. 90%), affording acceptable yield and selectivity (Table 1, entry 5). With optimized reaction conditions in hand (Table 1, entry 5), we then examined the generality of this four-component radical cascade reaction using xanthates 1, olefins

• functionalized keto-aldehydes [22], aminoalcohols [30], triazoles [31], just to name a few. A reaction mechanism is finally proposed for the four-component cascade reaction, which is depicted in Figure 2 [22][23][24][32][33][34]. Initially, α-carbonyl radical A [8] was generated by the reaction of the

• radical which sustains the radical chain. Since radical B can also add to sulfonyl oxime ether 3a, we used high CO pressure conditions to encourage the radical carbonylation to form acyl radical C. Conclusion In summary, we demonstrated that a four-component radical cascade reaction, between xanthogenates

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• -enynes through lithiation, borylation and rearrangement of cis or trans-alkynyloxiranes. This cascade reaction is stereospecific, probably due to the stereocontrolled group transfer from boron to the adjacent oxiranyl carbon in an oxiranylborate complex intermediate, followed by an internal bora-Wittig

SO₂F₂-mediated transformation of 2'-hydroxyacetophenones to benzo-oxetes

• Revathi Lekkala,
• Ravindar Lekkala,
• Balakrishna Moku,
• K. P. Rakesh and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 976–980, doi:10.3762/bjoc.15.95

• protocol for the transformation of 2'-hydroxyacetophenones to benzo-oxetes. This SO2F2-mediated cascade reaction showed exceptional functional group tolerance and a broad substrate scope which, to the best of our knowledge, is the first example of employing cheap and abundant 2'-hydroxyacetophenones as

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• products, showing that both enantiomers of NPP were converted with similar efficiency. These results clearly rule out (S)-NPP, but rationalise (R)-NPP as an intermediate in the cyclisation mechanism of BbS, and are in favour of the (S)-bisabolyl cation (A) to be deprotonated to 5 within the cascade

• reaction (Scheme 1, path A) [24][25][26], although the stereochemical link between NPP and A could not be demonstrated experimentally in this study. The formation of (R)-NPP from FPP as a 1,3-syn-allylic rearrangement can be rationalised in a binding mode of FPP, in which OPP is located on a defined face

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• step reaction arrangement starting from pyranose 4 was set up. Scheme 4 shows this setup of a suitable cascade reaction in which DBU, trichloroacetonitrile and pyranose 4 were pumped through the first flow reactor (R1) followed by the addition of the alcohol and TMSOTf through the second reactor. Table

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• photoredox catalysis oxidative radical ring-opening and cyclization of cyclopropyl olefins 83 with bromides 84 for the synthesis of partially saturated naphthalenes 85 in moderate to excellent yields (Scheme 19) [97]. It was the first example for alkylation, ring-opening and cyclization cascade reaction of

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• ways and 20c is a precursor to an API. Another method for benzothiopene construction is seen in Kumar and co-workers’ report describing a dehydrogenative oxytrifluoromethylation cascade reaction of 1,6-enynes, catalysed by phenanthrene-9,10-dione (PQ) (Ered*(cat/cat•−) +1.6 V vs SCE) using visible

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• -catalysed cascade reaction involving rearrangement via N–O bond cleavage [14]. While divalent copper acetate and copper chloride did not show any catalytic activities (Table 1, entries 1 and 2), more Lewis acidic copper complexes, such as [Cu(MeCN)4](PF6)2 and [Cu(OTf)]2·toluene, afforded the corresponding

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• catalyzed cascade reaction to afford alkylidenefluorenes 49 (Scheme 17) [57]. In terms of mechanism, a Pd(0)/Cu(I)-catalyzed Sonogashira coupling reaction from the iodonium salt 48 delivers a 2-alkynyl-2’-iodoarene 50 that, then, cyclizes to 51 via insertion of the Pd(0) species into the iodoarene moiety

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• easy to recycle [3][4][16][17]. On the other hand, the additional incorporation of the former iodoarene waste into the reaction product via a cascade reaction does not only improve the overall AE of a chemical reaction but also directly leads to highly functionalized target molecules. A rough estimate

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• , namely: (polymer) vesicles, micelles, dendrimers and nanogels. The ability and efficiency of catalytic nanoreactors to carry out organic reactions in water, to perform cascade reaction and their ability to be recycled will be discussed. Keywords: catalysis; dendrimers; green chemistry; nanogels

• reference [67]. Suzuki−Miyaura couplings with, or without, ppm Pd. Conditions: ArI 0.5 mmol 3a, Ar’B(OH)2 (0.75–1.00 mmol, 1.5–2.0 equiv) 3b, *with 200 ppm of Pd(OAc)2. Adapted from reference [70]. Copyright 2016 American Chemical Society. Cascade reaction with GOx and Myo. Adapted from reference [82

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• dehydratase. The dehydrated product is then reduced through a 3-step-cascade reaction (catalysed by 3 different enzymes) giving the final dehydroxylated product. 7-OH epimerization: shift the equilibrium Chemical epimerization of CDCA into UDCA The second step of UDCA synthesis from CA, is the epimerization

• formate is cheap and, because of the gaseous nature of CO2 as product, the equilibrium of the reaction is entropically favoured. Pedrini et al. in 2006 [33] reported the successful epimerization of CDCA to UDCA using a redox-neutral cascade reaction, with two NAD+-dependent dehydrogenases. In this way the

• Fusarium merismoides VKM F-2310. The possibility to access that kind of chemical and chemo-enzymatic reactions pave the way for the design of other unexplored routes for the production of UDCA (example in Figure 8). In addition, other reported enzymes can eventually play a role in the cascade reaction

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• double labeling of the mRNA cap with alkyne moieties could also be achieved based on a recently reported enzymatic cascade reaction [99]. In this system a Se-propargyl-modified AdoMet analogue (SeAdoYn [100]) was prepared enzymatically from the respective methionine analogue and ATP by a methionine

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• was obtained predominantly: the α-aryl-β-trifluoromethyl amide 6. This compound was determined to be issued from a trifluoromethylation/1,4-aryl shift/desulfonylation cascade reaction (Scheme 7). This reaction could be performed on various N-aryl,N-tosylacrylamides with moderate to good yields. The

• species 7 then underwent an aryl migration/desulfonylation cascade reaction to furnish intermediate 8. In the case of an aryl substituted substrate, this nitrogen radical being stabilised, it directly performed an hydrogen abstraction on acetonitrile to lead to the corresponding α-aryl-β-trifluoromethyl

• compound, albeit in low yield and with poor regio- and diastereoselectivity (Scheme 19). Interestingly, the authors proposed a mechanism involving a chain propagation pathway, in contrast to the work of Jung and Han. A similar cascade reaction was also performed on diethyl 2-allyl-2-(3-methylbut-2-en-1-yl

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• (Scheme 11) [30]. Amino- and azotrifluoromethylation of alkenes: Alkene trifluoromethylation was applied to the construction of indole, pyrazole and pyridazinone moieties via a multicomponent cascade reaction developed by Antonchick and Matcha in 2014 [31]. The method was based on the reaction between

• and co-workers reported the use of CF3SO2Na in combination with iodide pentoxide in a similar way to their iodotrifluoromethylation of alkenes (see earlier in the text) [42] (Scheme 29a) [51]. Interestingly, this cascade reaction was also applied to enynes for the synthesis of pyrrolidines 52 (Scheme

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• -addition by the activated C=C double bond and subsequent intramolecular recyclization of the intermediate with the amino group involved. Keywords: cascade reaction; diaminoimidazoles; HPLC–HRESIMS; imidazo[1,5-b]pyridazines; itaconimides; Introduction Among the numerous bicyclic fused imidazole

• the HPLC–HRESIMS monitoring of the reaction confirm its selectivity. Conclusion In summary, a new regioselective and chemoselective cascade reaction of N-arylitaconimides with 1,2-diamino-4-phenylimidazole as 1,3-C,N-dinucleophile was developed to synthesize tetrahydroimidazo[1,5-b]pyridazines. The

Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• phthalides in good to excellent yields. Conclusion: A concise and efficient synthesis strategy of 3-substituted phthalides from 2-formylbenzoic acid and β-keto acids via a catalytic one-pot cascade reaction in glycerol has been accomplished. Keywords: β-keto acid; decarboxylation; glycerol; one-pot cascade

• functional group compatibility and ingenious construction of molecular architectures [11][12][13][14]. Consequently, an efficient synthesis of 3-substituted phthalides via a one-pot cascade reaction is still in high demand. An analogous approach was described involving a catalytic sequence of the aldol

• reaction; phthalide; Introduction The phthalides, also known as isobenzofuran-1(3H)-ones, are an important class of heterocycles which are of continued interest for chemists [1][2]. 3-Substituted phthalides, which are recognized as versatile building blocks found in a large number of bioactive compounds