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

• for the first time an enantioselective C-2 alkylation of pyridine using a chiral phosphine oxide-ligated Ni–Al bimetallic catalyst system and the protocol was found effective for a wide range of pyridines including unsubstituted pyridines, C2, C3 and C4-substituted pyridines and complex pyridines

• containing bioactive molecules (Scheme 10). To attain enantioselectivity a chiral phosphine oxide (43)-ligated Ni–Al bimetallic catalyst was used that was critical in improving the reactivity and controlling the selectivity of the reaction. Further, based on deuterium labelling experiments, KIE studies, and

Synthesis, structure, and properties of switchable cross-conjugated 1,4-diaryl-1,3-butadiynes based on 1,8-bis(dimethylamino)naphthalene

• Semyon V. Tsybulin,
• Ekaterina A. Filatova,
• Alexander F. Pozharskii,
• Valery A. Ozeryanskii and
• Anna V. Gulevskaya

Beilstein J. Org. Chem. 2023, 19, 674–686, doi:10.3762/bjoc.19.49

• compounds 7a–e in 42–62% yields, but also gave higher amounts of products 9a–e (10–30%). Thus, the Pd- and phosphine-free Castro–Stephens coupling was a good enough alternative to synthesize alkynes 7. The structure of the double alkynylation product 9e was confirmed by X-ray diffraction data (see

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

• (phosphite/phosphine-pyridine amide, phosphine-sulfoxide, phosphoramidite, MINBOL, see Figure 1) and they usually showed excellent diastereoselectivity (dr >20:1). The catalytic systems even with low catalyst loadings tolerated both electron-donating and withdrawing groups on the aromatic substituents

• (Scheme 16). Within the framework of these domino reactions, we have mainly employed ferrocenyl phosphane ligands such as Taniaphos or Josiphos. In collaboration with Prof. Schmalz from Cologne University, we have also tested phosphite-phosphine ligands (e.g., L15) from their lab. The advantage of these

• of α,β-unsaturated phosphine oxides 149 [79]. Their work also included an example of the consecutive trapping of the enolate by MeI (Scheme 38). Using the (R,Sp)-Josiphos ligand (L17), the product of the tandem reaction (150) was gained in 63% yield (dr 5.2:1). At the beginning of the new decade

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• . Unfortunately, with this catalyst, repeatability problems were detected (yield fluctuation of approximately 20%) which could be assigned to the low solubility of this catalyst in toluene. In order to overcome these problems, we synthesized triruthenium carbonyl complexes with phosphine ligand(s), namely

• (triethoxysilyl)ethyl)phosphine L1 or triphenylphosphine [40][41][42]. Their synthesis, well-described in the literature, is detailed in Supporting Information File 1 (pp. S3–S6). Moreover, a kinetic study carried out in batch in the presence of the [Ru3(CO)11(L1)] (comp1), [Ru3(CO)10(L1)2] (comp2) or [Ru3(CO)9

• °C in toluene for 1 h with 0.33 equiv of comp4 [Ru3(CO)11(PPh3)], a catalyst analogue to comp1 but bearing a less expensive phosphine ligand (Scheme 5A). The chosen ratio of imine to catalyst was consistent with the stoichiometric amounts needed to form the postulated intermediate. The temperature of

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

• used directly which showed comparable yields. The authors also reported preliminary results for an asymmetric variant of the reaction using (R,R)-Ph-BPE as a chiral ligand. Although the use of the chiral phosphine ligand resulted in slightly diminished yields, the authors were able to achieve ees up to

• catalytic cycle starts with a diaryl Fe(II)–(S,S)-chiraphos complex 80 being generated through the reduction of FeCl3 with excess diarylzinc in the presence of the phosphine ligand. Side-on coordination to the exo face of the azabicycle 77a generates 81 where subsequent migratory insertion affords the alkyl

• after dissociation. Alternatively, 205 can undergo a ring closure followed by a subsequent C–P-bond cleavage causing a ring opening resulting in 207. Intramolecular SN2’ and elimination of the phosphine oxide generates the final product 202e which the authors propose is stereoselective due to

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

• additional functionalization steps the key intermediate 128. This compound constituted the substrate for the Pd-promoted intramolecular cyclization. In this case, an enol triflate was used instead of an alkenyl halide which required the presence of an electron-rich phosphine, a lower temperature (50 °C

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• afforded various functionalized oxindoles featuring a C3 quaternary stereogenic center. Mechanistic experiments suggest a radical mechanism. Keywords: decarboxylative cascade cyclization; iodide catalysis; metal-free photocatalysis; oxindole; phosphine catalysis; Introduction Radical-initiated cascade

• advantage of circumventing the need for external redox additives and/or noble metals, using readily available and cost-effective NaI and PPh3 under mild reaction conditions. In a broader context, phosphine organocatalysis is probably still underappreciated in organic synthesis, and could lead to important

• run in a similar fashion to related well-documented previous reports [54][68][69][70][71][72][73][74][75][76][77], through a light-induced, phosphine-assisted, intermolecular electron transfer from sodium iodide to the redox-active ester. Conclusion In summary, we developed an effective photocatalytic

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• referenced to anti-30 rather than H3PO4, while here all the values were calculated with reference to H3PO4, before being scaled. As the final example, Katz reported in 1966 [87] the reaction of cyclooctatetraene dianion with PhPCl2 to give a single phosphine product 32 having an unusually high field 31P NMR

• the corresponding phosphine oxides 33[O] and 34[O] with chemical shifts of 38 and 26 ppm, respectively (Figure 7). Identification of the isomers by 31P NMR would represent a nice example of the utility of the calculations described here. Results for 33, 34, 33[O], and 34[O] all confirmed the 1966

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

• kind of reaction engaging the azido group in the CD chemistry is the phosphine imide reaction [30][31]. This transformation involves triphenylphosphine and carbon dioxide to convert azide into isocyanate [31], allowing coupling with amines or other nucleophile groups. It is interesting to note that the

• methylated primary rim based on the remarkable methylation ability of methyl tosylate with relatively mild bases at solvent-free conditions has been developed. It has been proved that using Lewis acid in the phosphine imide reactions with CDs can increase the reactivity of some low-reactive compounds, giving

Mechanochemical bottom-up synthesis of phosphorus-linked, heptazine-based carbon nitrides using sodium phosphide

• Blaine G. Fiss,
• Georgia Douglas,
• Michael Ferguson,
• Jorge Becerra,
• Jesus Valdez,
• Trong-On Do,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2022, 18, 1203–1209, doi:10.3762/bjoc.18.125

• . 31P MAS NMR of a) g-h-PCN and b) g-h-PCN300. Asterisks denote spinning sidebands. Calculated structures for a) corrugated (edge facing), b) corrugated (single layer), c) layered g-h-PCN and d) phosphine paddlewheel. a) Mechanochemical synthesis of g-PCN from sodium phosphide and trichlorotriazine

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

• examined a series of reactions of symmetric and asymmetric secondary phosphine oxides with 2-pyridinecarboxaldehyde (2a), which produced the corresponding O-phosphination products (Scheme 2). Diarylphosphine oxide substrates with either electron-withdrawing or electron-donating groups tethered to the

• phenyl ring were well tolerated, and the phosphinate products 3ab–ah were obtained in moderate to good yield. The steric hindrance effect had a significant influence on the outcome of the reaction. For the phosphine oxide substrate 1i bearing an ortho-methyl-substituted phenyl group, the desired product

• system was further demonstrated with various unsymmetrically substituted phosphine oxides under the standard conditions. When the aryl group in the diarylphosphine oxide substrate was replaced by one or two alkyl groups or an ethoxy group, the transformation could also be achieved in moderate to good

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

• )phosphine (57) with two atom-equivalents of sulfur in refluxing benzene, affording the zwitterionic 2-aminobenzyl(phenyl)dithiophosphinic acid 58 in 80% yield. It was converted to 2-phenyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfide (59) in 91% yield by heating at 100–120 °C under vacuum (Scheme 10) [30

• co-workers prepared quinoline-fused 1,2-azaphospholine 2-oxides 217 in approximate 80% yield from 2-azidoquinoline-3-carbaldehydes 216 and tris(dimethylamino)phosphine in THF with water as solvent. It was mentioned that 2-azidoquinoline-3-carbaldehyde 216 and tris(dimethylamino)phosphine first

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• various phosphine ligands [62] for this reaction (Table 1, entries 1–8). Interestingly, we found that tri-tert-butylphosphonium tetrafluoroborate (t-Bu3P·HBF4) provided the borylation product 3a in excellent yield (92%, Table 1, entry 1), with a small amount of the protonation product 4a (5%, entry 1

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• Hui Zheng Ying Han Jing Sun Chao-Guo Yan College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.18.68 Abstract The tri(n-butyl)phosphine-catalyzed reaction of isatylidene malononitriles and bis-chalcones in chloroform at 65 °C afforded

• functionalized spiro[cyclohexane-1,3'-indolines] in good yields and with good diastereoselectivity. On the other hand, the tri(n-butyl)phosphine-catalyzed reaction of 3-(ethoxycarbonylmethylene)oxindoles and bis-chalcones gave functionalized spiro[cyclohexane-1,3'-indolines] with different regioselectivity

• . Additionally, the tri(n-butyl)phosphine-promoted domino annulation reaction of isatins and ethyl isatylidene cyanoacetates produced spiro[indoline-3,2'-furan-3',3''-indolines] in satisfactory yields. Keywords: isatin; spiro[cyclohexane-1,3'-indoline]; spiro[indoline-3,2'-furan-3',3''-indoline]; spirooxindole

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

• molecular host to modulate the reactivity. Recently, Reek and co-workers have constructed an M12L24 nanosphere by treating the bispyridyl 120° ligand 30 with a Pd(II) precursor [72]. Here, the ligand 30 is optimally functionalized with a phosphine gold(I) chloride moiety so that the metal catalyst will

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• (Scheme 11). Lower yields were observed, when the reaction was carried out in the absence of either phosphine, CuI or Fe powder. Although the reaction proceeded in the absence of Fe powder, the yield of the alkyne product was lower than that by the addition of iron powder. Various substituted aryl iodides

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• variety of enantioenriched 1,5-dihydro-2H-pyrrol-2-ones [20]. The development of any area is critically dependent on the understanding of underlying features and relationships. Slugovc and co-workers provide such mechanistic investigation of phosphine-catalyzed Michael additions [21]. Chiral

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• polarity solvents, of a novel class of diametric phosphine gold(I) cavitands characterized by a 1,2,3-alternate geometry. Preliminary catalytic studies were performed on a model cycloisomerization of 1,6-enynes as a function of the relative orientation of the bonded gold(I) nuclei with respect to the

• dictate the position of the metal centers, we reasoned on the possibility to design a novel generation of diametric phosphine gold(I) cavitands exploiting a calix[6]arene scaffold characterized by a 1,2,3-alternate conformation. As working hypothesis, this geometry would segregate two catalytically active

• phosphine ligand implanted on the aromatic ring (entry 5, Table 1). Interestingly, this effect was substantially improved with the use of the calix[6]arene-based complex C(AuCl)2 (entry 6, Table 1). Overall, the ortho-substituted macrocycle C(AuCl)2 displayed an enhanced selectivity, with respect to the

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• oxidation could be minimised by improved cleavage conditions under argon. Replacing sSPhos by tri(o-tolyl)phosphine (P(o-Tol)3), that had successfully been applied for peptide cyclisation by on-resin SMC [78][80], led to incomplete conversion. The cyclisation of the same peptide with the regioisomer 6

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• scaffold for a variety of natural products, bioactive compounds and pharmacological agents [79] as well as for a variety of chiral phosphine ligands [80]. As a result, the preparation of axially chiral arylpyrroles has been one of the most important areas of investigation in synthetic chemistry. In the

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• cooperative steric hindrance based on bulky substituents at the 2,9-position of the phenanthroline moiety [32][33]. Alternatively, heteroleptic CuI complexes with phenanthroline and bulky chelating phosphine ligands were also synthesized [30][34][35]. The photophysical properties are dramatically modified by

• ] discovered the asymmetric cross-coupling of racemic tertiary alkyl halides 43 with carbazoles or indoles 44 in the CuI/chiral phosphine system. Under irradiation conditions, excitation of the copper–nucleophile complex A results in the excited state species B that engages in the electron transfer with the

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• precursors have also been widely explored in the past decades. These reactions typically proceed under the catalysis of a nucleophilic tertiary amine or phosphine, and no metal catalysts are needed, which makes this strategy more synthetically useful for the construction of allyl-substituted scaffolds

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• in 2020, an enantioselective C–H annulation of ferrocenylformamides with alkynes was achieved by the Ye group enabled by Ni-Al bimetallic catalysis and a chiral secondary phosphine oxide (SPO) ligand [35]. Hou et al. also reported the asymmetric C−H alkenylation of quinoline- and pyridine-substituted

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• the previous sections. For example, catalyst 25 bearing a nucleophilic aminoalcohol functionality interacts with the boronic acid reagent in the Reissert-type reaction with acylated quinolines (Scheme 5b) [36], while the phosphine moiety in the bifunctional phosphinothiourea catalyst 31 allows for

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• were taken as partners in a Buchwald coupling (Scheme 22a) [44]. On the other hand, in 2015, Organ’s group performed a phosphine-ligand free Buchwald amination of 5-chloroindole (164) with amine 165 to give the desired product 167, where the use of the Pd-PEPPSI-IPentCl precatalyst 166 in presence of