Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• reaction times. Notably, 6-endo N-cyclization to form 2-piperidinones was not observed (Scheme 5). Using this protocol, a series of spiro-β-lactams were synthesized, with only the structure of the aryl moiety being varied. It is noteworthy to consider that the formation of two vicinal quaternary chiral

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• . Keywords: azidation; nitration; organocatalysis; oxidation; quaternary ammonium iodides; Introduction Organic compounds containing an azide functionality are highly valuable synthesis targets that offer considerable potential for various applications and further manipulations [1][2][3][4][5][6][7][8][9

• ][25][26][27][28][29][30][31]. Such oxidative coupling strategies of two inherently nucleophilic species allow for the direct utilization of simple starting materials in an efficient manner and especially the use of quaternary ammonium iodides as redox active catalysts has emerged as a powerful

• accessible starting materials. Our group has a longstanding research interest in α-heterofunctionalization reactions under oxidative conditions [37][38][39] and we [30], as well as others [28][29][31], have recently also explored the use of simple quaternary ammonium iodides for oxidative α-azidations of

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• , Iran 10.3762/bjoc.20.134 Abstract We herein report the asymmetric organocatalytic addition of azlactones to allenoates. Upon using chiral quaternary ammonium salt catalysts, i.e., Maruoka’s binaphthyl-based spirocyclic ammonium salts, the addition of various azlactones to allenoates proceeds in a β

• ; quaternary ammonium salt catalysis; Introduction The development of asymmetric synthesis routes to access non-natural amino acids has for decades been one of the most heavily investigated tasks in organic synthesis and catalysis-oriented research [1][2][3][4][5][6][7][8][9][10][11][12][13]. As a consequence

• transformation under asymmetric ammonium salt catalysis [35][36][37][38] and the results of these investigations are outlined in this contribution (Scheme 1C). Results and Discussion We started our investigations by testing the quaternary ammonium salt-catalyzed addition of azlactone 1a to allenoate 3a (Table 1

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• intermediates in organic synthesis for the construction of all-carbon-substituted quaternary centers (Figure 1A). However, conventional methods for the synthesis of tertiary alkylnitriles such as direct functionalization of alkylnitriles [10] and hydrocyanation of alkenes [11][12][13][14] are typically hindered

• functional handles for further elaboration. Notably, tertiary arylacetic acids can also be well tolerated to yield nitriles with quaternary carbon centers in good yields (17 and 18). Simple carboxylic acids without functional groups at the alpha position to stabilize the corresponding carbon centered

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• -(−)-tryptophan via the common intermediate, (+)-vellosimine (74). The protocol reflected the stereocontrolled formation of the C-16 quaternary center in 76 created via an intermolecular crossed-Cannizzaro reaction of 75, generated from 74, using 37% aqueous formaldehyde. The quaternization proceeded in excellent

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• minor products as well (7–20% yields). The formation of biphenyls 44 can be explained by 1,4-addition and ring-cleavage to give intermediate AH, aldol reaction (intermediate AI), migration of the ester group from the quaternary carbon to the phenolic oxygen atom (intermediate AJ) and aromatization. The

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• oxygenases. Notably, AlpJ-family oxygenases stand as a pioneering example of enzymes capable of catalyzing oxidative reactions in either an FADH2/FMNH2-dependent or -independent manner. Up to date, many oxygenases from diverse evolutionary families, featuring varied protein folds and quaternary arrangements

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• C60 and quaternary carbons of the Dip groups are indicated by grey circles. ORTEP drawing of 3 showing thermal ellipsoids at the 50% probability level at 100 K. Hydrogen atoms are omitted for clarity. (a) Partial structures of isomers of Dip2SiC60. (b) Optimized structures of 2a and 2c. Hydrogen atoms

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• methyl groups at δH (0.83, 0.87, 0.98 and 1.77). Its 13C and DEPT NMR spectra showed 15 carbon resonances, including four methyl groups, four methylenes, four methines, and three quaternary carbon atoms. This information suggests that it may be a drimenol congener and the structure was further supported

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• esters for the construction of quaternary carbons via conjugate addition of 3° radicals [39][40]. In general, this transformation operates under a reductive quenching photocatalytic cycle, requiring a stoichiometric reductant (Scheme 4A). Both TM complexes, and organic dyes such as eosin Y [41][42][43

• [119] (Scheme 37A). Recently, Lumb and co-workers showcased the use of NHPI esters in key radical cyclizations, allowing the synthesis of diverse dibenzocyclooctadiene lignans [55] (Scheme 37B). A Ru-catalyzed cyclization was employed to construct the quaternary stereocenter in taiwankadsurin A

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• the orange plates of compound 4c belonged to the monoclinic P21/c group. Due to the asymmetry of the quaternary carbon atom adjacent to the carbene center, the latter compound crystallized as a racemic mixture. Solutions of MIC·CS2 zwitterions 6a–f in CD2Cl2 or CDCl3 employed for NMR analyses were

• contrast with the most common cyclization processes leading to imidazol(in)ium derivatives, which afford symmetrical products with identical substituents on both nitrogen atoms [82]. Although cyclic aldiminium salts are less readily available, they feature a quaternary carbon atom next to the carbenoid

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• ]. Importantly, these methodologies could also be smoothly extended to the synthesis of isoquinolinediones, which borne a quaternary carbon center. Furthermore, Yatham and his colleagues unveiled the first NaI/PPh3-mediated photocatalytic decarboxylative cascade cyclization of 2-isocyanobiaryls 44 with alkyl N

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• 21.0 and one at δC 25.2 attached to the alternariol basis skeleton (Figure 2, Table 1); four methines (δC 117.0, 101.1, 109.6, 108.6), and eleven quaternary carbons including the signal of the lactone carbon at δC 158.5 (C-6) and those of the three sp2 oxygenated carbons at δC 156.9, 154.2, and 153.2

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• thus the sense of chiral induction for the 1,4-addition reactions reported in Table 2. Tandem 1,4-addition–aldol condensation reactions We then went on to consider tandem 1,4-addition–aldol condensation reactions (Scheme 6), which offer the interesting prospect of generating an all-carbon quaternary

• view, the reported protocols are relevant as they offer a new, direct and modular route to enantioenriched α-mono- and α,α-disubstituted β-amino acids (β2-amino acids and β2,2-amino acids), with, for the latter, the noteworthy stereocontrolled construction of an all-carbon quaternary stereocenter

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• -workers [61] extended the application of NHC–copper catalysts to the conjugate addition of boronates to acyclic α,β-unsaturated carboxylic esters, ketones, and thioesters leading to the enantioselective formation of boron-substituted quaternary carbon stereogenic centers (Scheme 43). All transformations

• transformations of sterically congested substrates, including those carrying a quaternary center not only proceeded efficiently but also were more selective. The NHCs with larger aryl units deliver higher selectivity ((Z/E: >98:2). Cazin and co-workers [83] instead used [IMes–CuCl] as catalyst for the borylation

• and co-workers (Scheme 72) [94]. Some of the characteristic features of this methodology are: enantioselective formation of the quaternary stereocenters, broad substrate scope, high enantioselectivity, and branched:linear selectivity. Furthermore, the NHC–Cu complex incorporating the chelating N-2

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• synthesis of compounds with quaternary centers and natural products with high structural complexity. In 2014, Li et al. reported a CuCl2-catalyzed cross-dehydrogenation coupling reaction of C(sp3)–H bonds adjacent to an ether oxygen and the C(sp3)–H bonds at the α-position of a carbonyl functionality in the

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• methylene groups at δH 2.65/2.69 (H2-2') and δH 2.69/2.72 (H2-4') to an ester carbonyl (δC 172.4, C-1') and a carboxyl (δC 175.0, C-5'), respectively. In addition, both methylene groups together with a methyl singlet at δH 1.38 (s, H3-6') disclosed key HMBC correlations to a quaternary oxygenated carbon at

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• process was achieved through the C3–H functionalization of indole derivatives 4. The nucleophile favors the attack at the imine carbon included in the seven-membered ring of compound 8 to generate an aza-quaternary stereocenter containing trifluoromethyl, pyrrole/indole, and benzoazepinoindole moieties

• than with indoles (Scheme 3) [26]. In 2018, Kim and co-workers developed an aza-Friedel–Crafts protocol involving pyrroles 9 as the π-nucleophile in combination with cyclic N-sulfimines 12. The chiral phosphoric acid P4 was used to catalyze the introduction of a pyrrole-substituted aza-quaternary

• for the functionalization of the C3–H bond in indoles 9 in the presence of BINOL-derived chiral phosphoric acid P6 as the catalytic agent. They utilized trifluoromethyl ester-substituted N-unprotected imine 15 as the potential electrophile to install an aza-quaternary stereocenter in the C3 position

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• amines 52 with 2,5-DMTHF (2) under a L-(+)-tartaric acid-choline chloride based deep eutectic solvent as green medium (Scheme 25a). Deep eutectic solvents (DESs) are mainly synthesized by mixing quaternary ammonium salts and hydrogen-bond donors. In this study, various combinations of salts and hydrogen

• bond donating groups were investigated. Among these, the DES prepared by mixing quaternary ammonium salts choline chloride (ChCl) and the hydrogen-bond donor L-(+)-tartaric acid gives the best result. Moreover, L-(+)-tartaric acid–ChCl acts as both solvent and catalyst for pyrrole synthesis. This

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• compound 8b revealed only a single signal of a carbonyl carbon at 193.2 ppm, and a signal of a quaternary carbon at 167.0 ppm, which could not be assigned. These spectral data prompted us to reconsider the structure of compound 8b. The reaction of chlorinated nitrostyrene 2b with acetylacetone (3b) was in

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• lactam 2 structure involving the replacement of a quaternary carbon carrying two electron-donating methyl groups with an electron-withdrawing carbonyl group (2b → 3). The starting isoquinoline-1,3(2H,4H)-dione was prepared [31] from homophthalic acid and then brominated with NBS to give 4

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• sp2), one carbonyl carbon, and two sp2 quaternary carbons. The 1H–1H COSY spectrum (Figure 2 and Figure S29 in Supporting Information File 1) of compound 7 disclosed the existence of correlations of H2-2 (δ 2.29, 2.08)/H-3 (δH 1.91, 1.93)/H2-4 (δH 1.38, 1.24)/H2-5 (δH 2.03, 2H)/H-6 (δH 5.12), H-3 (δH

• carbon, and two sp2 quaternary carbons. A comparison of the NMR data of compound 8 (Table 4) with that of compound 7, indicated that both compounds possess the same general skeleton structure, with the only difference being an additional methine group in compound 8. The 1H–1H COSY correlations (Figure 2

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

• either on harsh reaction conditions or require the preactivation of substrates, which limits their synthetic efficiency. A photocatalytic quaternary C-3 alkylation has also been reported recently (Scheme 1A) [21][22]. During the course of our study, the Wu group reported a solvent-controlled

• aerobic oxygenation approach to imidazo heterocycles II to install the hydroxymalonate unit onto I through sequential photoredox C–H functionalization. Till date, there is no report of the direct incorporation of a quaternary hydroxyalkyl, specifically a hydroxymalonyl group at the C-3 position of IPs

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• . The 13C NMR and DEPT spectra, combined with HMQC correlations (Table 1) showed 20 resonances for carbon signals accounting for four methyls, five sp3 methylenes, five methines (two olefinics at δC 111.6, 109.6), and six quaternary carbons (one carbonyl at δC 169.8, two olefinics at δC 163.8, 149.3

• -lactone functionality. The 13C NMR and DEPT spectra in combination with HMQC data (Table 1) showed resonances of 44 carbons which were classified as nine methyls, 11 methylenes, 11 methines (three oxygenated sp3 at δC 73.7, 69.4, 68.8), and 13 quaternary carbons (four carbonyls at δC 197.9, 170.7, 170.4

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

• . presented their work on the asymmetric desymmetrization of cyclopentene-1,3-diones 5 (Scheme 3) [23]. Following the Cu(OTf)2-catalyzed conjugate addition of R2Zn, the enolate 6 was trapped by several aromatic aldehydes 7. These complex chiral cyclopentane derivatives 8 bearing all-carbon quaternary

• contains six contiguous stereogenic centers out of which four are all-carbon quaternary stereocenters. The authors have achieved the stereoselective synthesis of waihoensene for the first time with a 3.8% overall yield (15 steps) (Scheme 59). The construction of the triquinane core included a Cu-catalyzed

• of a synthetic chemist, the most remarkable feature of this structure is the highly substituted cyclopropane ring incorporating two all-carbon quaternary centers, while the whole structure contains 7 stereocenters. Xu et al. recently demonstrated their 13-step total synthesis of (−)-peyssonnoside A