Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• organoboron reagents were realized [12]. Also, in terms of suitable Michael acceptors as substrates, unsaturated ketones, aldehydes, esters, thioesters, amides, alkenyl heterocycles and enoyl heterocycles became viable for conjugate additions. The maturity and robustness of this methodology is documented by

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• significantly affect the C–H alkylation reaction and the reaction also proceeded well with hydrazones 13 obtained from aliphatic aldehydes or ketones. Based on mechanistic experiments and DFT calculations, the reaction presumably proceeds via a Cu–carbene migratory insertion (Scheme 4b). In the presence of CuI

• hydrolyzed to get the corresponding ketones. In 2018, Albéniz and group [99] reported the direct C3-arylation of pyridines with the help of bipy-6-OH as coordinating ligand under palladium catalysis (Scheme 29). In most of the cases the arylated pyridines 152 were obtained as mixtures of ortho-/meta-/para

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

• stereoselective methodologies have been published that demonstrate the Cu- or Ni-catalyzed conjugate addition of organozincs to α,β-unsaturated ketones 14 followed by the reaction of the metal enolate with a nitroolefin (20) (Table 1) [30][31][32][33]. These reactions were facilitated by different ligand families

• nucleophile (R3Zn−) to the ketone with moderate yields but still good stereoselectivities (Scheme 9B). In 2018, Wang and co-workers extended the group of applicable electrophiles for the zinc enolate-based tandem reactions. Following the conjugate addition of Et2Zn to acyclic α,β-unsaturated ketones 41, they

• properties. In several cases the α-SCF3-substituted ketones 44 were isolated in good yields and enantioselectivities but with low diastereoselectivities. Even though no asymmetric catalyst was involved, Kawano et al. recently demonstrated an attractive one-pot procedure for preparing complex bicyclic and

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• ]. Based on its structure, many other inhibitors have been developed, such as vinyl sulfones, fluoromethyl ketones, and semicarbazides [8][9]. These inhibitors covalently bind to the nucleophilic thiol group of Cys234 in the active site of cathepsin C via a thioether bond. Phosphonates have been identified

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• a B‒O/B‒H transborylation in catalysis was the catalytic Midland reduction of propargylic ketones developed by Thomas to give enantioenriched propargylic alcohols (Scheme 10) [74]. The reaction was proposed to occur by enantioselective reduction of the propargylic ketone 42 by myrtanyl borane 43 to

• to give aldol-type products 61. Thomas reported the borane-catalysed diastereo- and enantioselective allylation of ketones with allenes and HBpin to give diastereo- and enantioenriched allylic alcohols, after workup (Scheme 15) [78]. The mechanism was investigated by single-turnover experiments and

• first example of Al‒O/B‒H exchange in catalysis was reported by Woodward, in the enantioselective catalytic hydroboration of ketones with HBcat as the terminal reductant (Scheme 23) [103]. A mixture of 1,1′-bi-2-naphthol (BINOL), 1,1'-binaphthalene-2,2'-dithiol (DTBH2), or 2-hydroxy-2'-mercapto-1,1

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• ]. Dihydrolimonene 25 was converted in 9 steps into compound 60 before subsequent RCM. As the authors knew G-I catalyst isomerizes β,γ-unsaturated ketones, G-II catalyst was chosen to produce bicyclic compound 61. Several additional steps were necessary to forge the last ring and obtain the core structure 63 of this

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• ; hydrozirconation; palladium catalysis; Schwartz's reagent; terpenes; Introduction Conjugated dienones are recurring structural motifs in natural products. Several biologically relevant compounds carry (2Ε,4E)-unsaturated ketones or the corresponding esters or amides. Selected examples are clifednamide H (1) which

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• synthesis by Taber that used dichromate as an oxidant [13] led to a less diastereoselective reaction furnishing the three ketones 9, 10, and 11 in a ratio of 36:2:5. The cis-conformation of the decalin backbone of 9 and 11 originates from the endo-selectivity of the Diels–Alder reaction and the boat

• the ratio of the minor diastereomers, the ketone mixture was treated with NaOMe, resulting in epimerization of 9, arriving at a 3:3:1 mixture of 9, 10, and 11. Unfortunately, a moderate amount of material was lost due to competing aldol reactions of the ketones. While compound 9 was epimerized to a

• concept proved to be difficult to achieve, but by optimization of different parameters of this Domino reaction, the required enantiomerically almost pure ketones 9–11 were obtained (Table 1). The Mannich reaction worked best using diisopropylammonium trifluoroacetate as the catalyst [22]. The isolation 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

• ) into cis-stilbene (62), via the dihydrodithiin intermediate 61 [58]. The addition of lithiated dihydrodithiins with aldehydes, epoxides or ketones are also all feasible, but sometimes require some more attention (Scheme 11). Palumbo and co-workers have found that substituted dithiins such as 50 can

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• reactions constitutes one of the main pillars of organic synthesis [1]. In this respect, the all-carbon Nazarov cyclization of divinyl ketones represents a direct method for the synthesis of five-membered carbocycles [2][3][4][5][6][7][8][9]. Variants of the Nazarov cyclization with substrates bearing one

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

• organocatalyst forms hydrogen bonds with both H2O2 and cyclic ketones [66]. A chiral Brønsted acid was used as chirality source and activator of H2O2 for an asymmetric sulfoxidation reaction [67] (Scheme 4B). It is generally accepted that in asymmetric Brønsted acid catalysis the activation of both the

• the side process of their overoxidation to aldehydes or ketones. In another work, 3-acetoxyquinuclidine showed improved yields compared to unsubstituted quinuclidine in the α-functionalization of N-Boc-substituted secondary amines [108], showcasing an amine cation radical activity tuning by the

• –H2O2 system the adducts of H2O2 and ketones (perhydrates) can also be active oxidative species [51]. Dioxiranes formed from ketones and hydroperoxides are electrophilic oxygen transferring agents used in epoxidation (including asymmetric variants) [131][132], CH-hydroxylation, and other oxidation

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• cyclohexanone (as well as other cyclic ketones) which delivered spiro-annulated 2-benzoxepines (such as 2a) along with a minor byproduct 3a identified by 1H NMR as the product of formal insertion of the rhodium(II) carbene species into the O–H bond of cyclohexanone enol form. This minor byproduct, on heating at

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

• aldol-type reactions, and reductive Mannich-type reactions using RhCl(PPh3)3 with Et2Zn [41][42][43][44][45][46][47]. The rhodium-catalyzed reductive aldol reaction of α,β-unsaturated esters with aldehydes or ketones gives aldol-type products in good to excellent yields (Scheme 1) [43][44]. In addition

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• , United Kingdom 10.3762/bjoc.18.151 Abstract The reactions of aromatic aldehydes and levoglucosenone promoted by methoxide gives bridged α,β-unsaturated ketones, formed by a series of oxa-Michael-initiated cascade reactions in yields of up to 91% (14 examples). A complex series of equilibria operate

• unreported mode of reaction between α,β-unsaturated ketones and aromatic aldehydes promoted by base. Results and Discussion The reactions of 1 with aromatic aldehydes and sodium methoxide in methanol were investigated at ambient and elevated temperatures (Table 1). In the reaction of benzaldehyde and 1 at 60

• bridged α,β-unsaturated ketones; however, these reactions do not involve initiation by an oxa-Michael addition [23][24]. The reaction between 1 and aromatic ketones under basic conditions is analogous to the well-known aldol/Michael cascade reaction observed between aldehydes and enolates giving di- and

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

• advantages over the related enol silyl ethers [24][25]: they are more stable towards acidic conditions, their electronic character contributes to high regioselectivity in cycloaddition reactions, and they can be converted to many other functions, including their hydrolysis to ketones [26]. In the other hand

• obtained when using equimolar amounts of both 19 and 11b (Table 1, entries 1 and 2). These disappointing results with alkyne 19 prompted us to investigate the coupling with an organometallic reagent derived from vinyl iodide 20. This reagent was already synthesized and coupled with acyclic ketones in

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• cycle can also lead to different reaction outcomes, e.g., rearrangements, desaturations or epoxidations. Multiple oxidation rounds, leading to aldehydes/ketones or carboxylic acids, are also commonly observed. Together, this versatile oxidative chemistry makes CYPs key enzymes in specialised metabolism

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• and Life, Beijing University of Technology, Beijing 100124, China 10.3762/bjoc.18.130 Abstract The electrochemical preparation of 2-aminothiazoles has been achieved by the reaction of active methylene ketones with thioureas assisted by ᴅʟ-alanine using NH4I as a redox mediator. The electrochemical

• protocol proceeds in an undivided cell equipped with graphite plate electrodes under constant current conditions. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diketones, can be converted to the corresponding 2-aminothiazoles. Mechanistically

• ], dyes [13], etc. These important features of thiazoles have driven intense interests in their facile synthesis [14][15][16][17]. Among various synthetic routes to the thiazole unit, the Hantzsch condensation of α-halo ketones (dielectrophiles) with various thioureas (dinucleophiles) should be the most

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• intramolecular aldol addition of ketones such as 7 (Scheme 2) [5]. Brønsted-acid catalysis leads via a transition state 8 to the aldol 9, while the use of chelating Lewis acids results via 10 in the epimeric aldol 11. This review is a collection of total syntheses of natural products where vicinal keto esters

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• accomplished the synthesis of phosphoric esters through a 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence [43]. A decade later, Chakravarty and colleagues reported the efficient synthesis of organic phosphates from ketones and aldehydes using n-BuLi as

• , all of the above transformations were carried out under basic conditions, and thus impose barriers for substrates that bear base-sensitive functional groups. More importantly, heteroatom-containing ketones and aldehydes have been proven to be challenging substrates for all of these existing systems

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• recently, two publications from the Werz group appeared concerning anodic activation of donor–acceptor cyclopropanes followed by their functionalization with arenes [43] or yielding oxy-ketones or 1,2-dioxanes [44]; the latter process was inspired by a previous report of Buriez [45]. The anodic

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• o-chloroarylketones are the starting material [27][28]. The preference for the use of o-bromo analogues is due to to the better yield obtained compared to using o-chloroarylhydrazones. However, the availability of commercial o-chloroarylaldehydes and o-chloroaryl ketones is greater than that of

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• proton-exchange membrane reactor is described. The reduction of enones proceeded smoothly under mild conditions to afford ketones or alcohols. The reaction occurred chemoselectively with the use of different cathode catalysts (Pd/C or Ir/C). Keywords: enone; hydrogenation; iridium; palladium; PEM

• reactor; Introduction Catalytic hydrogenation of α,β-enones is a significant transformation in organic synthesis [1]. Hydrogenation of enones can give ketones, allyl alcohols, and saturated alcohols, and the control of the chemoselectivity is important. Therefore, there have been numerous studies on the

• cathodic chamber and are reduced by the catalyst of the MEA to monoatomic hydrogen species (adsorbed hydrogen, Had) [22]. Thus generated Had reduces enones 1 to give the corresponding hydrogenated products (ketones 2 and alcohols 3). The expected advantage of PEM reactors is that the reactivity of Had

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• vinyl acetates has been developed to afford the corresponding α-fluorinated [26], -arylated [27], and -sulfenylated [28] ketones (Scheme 1B). In addition, electrochemical azidation [29][30][31][32][33] has also become a robust and reliable synthetic tool to incorporate azido functionality [34][35] into

• ketones, such as cyclohexanone (see Supporting Information File 1 for details). As illustrated in Scheme 3, the synthetic utility of α-azidoketone was further evaluated [37][38]. Click reaction between 2-azido-1-phenylethan-1-one (2) and ethisterone (28) [39][40][41] readily afforded the target triazole

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• alcohols [24], methoxides [23][25][26], carboxylic acids [27], amides [28], ketones [29][30], an exo-olefin [31], and lactones [32]. Elucidating the mechanisms of structural diversification is essential when considering the synthesis of unnatural azoxides by a synthetic biology-based approach. However

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• flowers of orchids among with the structurally related and better known Ambrettolide [(Z)-7-hexadecen-16-olide], having a sweet odor with “great tenacity and fixative power” [9][48]. Notably, and already in 1970, Story and co-workers described that cyclic ketones can be reacted with hydrogen peroxide