Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• site providing a trans relationship between the hydroxy and the phosphine substituents. Keywords: isopinocamphone; monoterpenes; phosphines; [2,3]-sigmatropic rearrangement; verbanone; Introduction Chiral phosphorus compounds, despite many years of research, still enjoy unflagging interest of many

• ], conjugated additions to enones [7], and allylic alkylations [8][9]. Another direction of research is the use of phosphines in organocatalysis [10][11] and bifunctional catalysis [12]. Several methods were developed to introduce the phosphine functionality to organic molecules. The reaction of organometallics

• with chlorophosphines, the reaction of metal phosphides with haloalkanes, and transition-metal-catalyzed cross-coupling reactions to form C–P bonds are the most widely used methods for the synthesis of phosphines [13][14]. Since phosphines are easily oxidized to phosphine oxides, the addition of

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• the presence of commercially available inexpensive salts (AgOTf, AgNO3) and eventually a (chiral) ligand. Such silver(I) complexes were prepared by using (bi)pyridine [19][23][24][25][26], phosphine [22][27][28][29][30], ditopic N/P [22] ligands and a few S/P and S/N ones [31][32][33][34]. None of the

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• synthesis via an Heck-type palladium-catalysed reaction according to the method of Harayama [30] (Pd(II)acetate/tri(o-tolyl)phosphine/K2CO3) did not lead to the expected alkaloid 3. Also the radical procedure published by Markgraf et al. [31] using AIBN and Bu3SnH and a photochemical cyclization protocol we

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• excellent yields with easy to separate byproducts. A year later, the same catalyst was employed for the nucleophilic fluorination of aryl bromides and iodides with AgF and KF [54]. Meanwhile, with a slight modification of the phosphine ligand, Buchwald developed a similar Pd(0) precatalyst [L2Pd]2(cod

• trifluoromethylation of vinyl triflates and nonaflates (Scheme 65). A variety of trifluoromethylated cyclohexenes were obtained using a catalyst system, which was composed of Pd(dba)2 or [(allyl)PdCl]2 and the monodentate biaryl phosphine ligand t-BuXPhos. Also, TMSCF3 and KF were more suitable to the

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• a microwave reaction vessel 3a (1.01 g, 5.00 mmol, 1.00 equiv) was mixed with styrene (651 mg, 6.25 mmol, 1.25 equiv), tris(o-tolyl)phosphine (61 mg, 0.20 mmol, 0.04 equiv), Pd2(dba)3 (92 mg, 0.10 mmol, 0.02 equiv) and NEt3 (863 ΜL, 0.63 g, 6.25 mmol, 1.25 equiv) and suspended in anhydrous DMF (6 mL

• mmol, 1.00 equiv), 1-fluoro-4-vinylbenzene (550 mg, 4.50 mmol, 1.50 equiv), tris(o-tolyl)phosphine (183 mg, 0.60 mmol, 0.20 equiv), Pd2(dba)3 (67 mg, 0.30 mmol, 0.10 equiv) and NEt3 (1.25 mL, 9.00 mmol, 3.00 equiv) in anhydrous DMF (4 mL). The reaction was conducted at 140 °C for 1.5 h. The raw product

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• . The effect of the solvent was then assessed. While no reaction took place in CH3CN (Table 1, entry 3), DMF (Table 1, entry 4) and DMSO (Table 1, entry 5) allowed the formation of 4a in 66% and 75% yield, respectively. The use of another bidentate phosphine such as dppe gave no improvement (Table 1

Microwave-assisted synthesis of N,N-bis(phosphinoylmethyl)amines and N,N,N-tris(phosphinoylmethyl)amines bearing different substituents on the phosphorus atoms

• Erika Bálint,
• Anna Tripolszky,
• László Hegedűs and
• György Keglevich

Beilstein J. Org. Chem. 2019, 15, 469–473, doi:10.3762/bjoc.15.40

• phosphorus atoms was synthesized by the microwave-assisted and catalyst-free Kabachnik–Fields reaction of (aminomethyl)phosphine oxides with paraformaldehyde and diphenylphosphine oxide. The three-component condensation of N,N-bis(phosphinoylmethyl)amine, paraformaldehyde and a secondary phosphine oxide

• affording N,N,N-tris(phosphinoylmethyl)amine derivatives was also elaborated. This method is a novel approach for the synthesis of the target products. Keywords: (aminomethyl)phosphine oxides; Kabachnik–Fields reaction; ligand; microwave; N,N-bis(phosphinoylmethyl)amines; N,N,N-tris(phosphinoylmethyl

• ][3][4]. In addition, a few Pt, Ru and Au complexes incorporating phosphine ligands show significant anticancer activity [5][6]. One of the most common synthetic routes to α-aminophosphine oxides is the Kabachnik–Fields (phospha-Mannich) reaction, where an amine, an oxo compound (aldehyde or ketone

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• H2O (ca. 6%) severely affects the phosphine-based catalysts Caz-I and Ind-II, while it has a less pronounced detrimental effect on the isopropyloxy-benzylidene catalyst HG-II. “On water” vs “in water” metathesis Hydrophobic catalysts are able to perform metathesis in aqueous mixtures. Blechert and

• , the presence of a Brønsted acid led to the protonation of one phosphine ligand rather than reacting with the ruthenium alkylidene moiety. Scavenging of the trialkylphosphine moiety resulted in a more active complex capable of initiating the ROMP of 2,3-difunctionalized norbornadienes and 7-oxo

• phosphine-based catalysts bearing quaternary ammonium tags 1 and 2. Synthesis of water-soluble catalysts 3 and 4 bearing quaternary ammonium tags. In situ formation of catalyst 5 bearing a quaternary ammonium group. Catalyst recycling of an ammonium-bearing catalyst. Removal of the water-soluble catalyst 12

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• [2,3]-sigmatropic rearrangement of the in situ-generated phosphinites 2a–h. Primary or tertiary cyclopropenylcarbinols reacted equally well, as shown with the formation of phosphine oxides 3a (94%), 3b (93%) and 3c (87%). The [2,3]-sigmatropic rearrangement of phosphinites 2d–h derived from secondary

• cyclopropenylcarbinols led to the corresponding phosphine oxides 3d–h (85–93%) as a 80:20 mixture of E/Z geometric isomers, regardless of the substituent of the alcohol (at C4) and of the cyclopropene (at C2, Scheme 2) [33][34]. The [2,3]-sigmatropic rearrangement of an optically enriched phosphinite 2f, prepared from

• ’ were considered which would lead to five-membered ring transition states in which the aryl group occupies a preferential pseudo-equatorial or a less favorable pseudo-axial orientation, respectively (Scheme 3) [33][34]. The authors also showed that phosphine oxide (E)-3f could be reduced to the

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• concomitant decomposition. As for Hoveyda-type catalysts 3b, 4b and 5b, they all disclosed lower activity than the parent complex HGII-SIMes, with catalyst 5b being the least efficient of all in this series (>97% conversion in 100 min). Finally, 6a as well as the phosphine-free 6b showed to be very poor

• 24b showed activities similar to that of GII-SIMes. They also exhibited different E/Z selectivities in CM transformations (e.g., Table 1, entry 2), and gave improved selectivities in a diastereoselective RCM reaction (Table 1, entry 3). Ledoux, Verpoort et al. described a series of phosphine

• unsymmetrical pyridine-containing Ru benzylidenes (Figure 13) with N-alkyl (49, 50), N-phenyl (51) and N-benzyl (52) substituents in comparison to their parent phosphine-containing catalysts 24a, 25a, 1a and 53 [27]. Complexes 49 and 52 were obtained as monopyridine adducts, while complexes 50 and 51 were

The activity of indenylidene derivatives in olefin metathesis catalysts

• Maria Voccia,
• Steven P. Nolan,
• Luigi Cavallo and
• Albert Poater

Beilstein J. Org. Chem. 2018, 14, 2956–2963, doi:10.3762/bjoc.14.275

• with ortho-methyl and isopropyl groups at both ortho positions of their phenyl ring. DFT results highlight the more sterically demanding indenylidenes have to undergo a more exothermic first phosphine dissociation step. Overall, the study emphasises advantages of increased steric hindrance in promoting

• the phosphine release, and the relative stability of the corresponding metallacycle over classical ylidene ligands. Mayer bond orders and steric maps provide structural reasons for these effects, whereas NICS aromaticity and conceptual DFT confirm that the electronic parameters do not play a

• the saturated NHC backbone of the SIMes ligand facilitates the phosphine dissociation since the Ru–P bond distance is longer [24][38]. This is corroborated via the corresponding lower MBO values. More interestingly, the Ru–CNHC bond is much shorter for SIMes, with a corresponding MBOs at least 0.030

The influence of the cationic carbenes on the initiation kinetics of ruthenium-based metathesis catalysts; a DFT study

• Magdalena Jawiczuk,
• Angelika Janaszkiewicz and
• Bartosz Trzaskowski

Beilstein J. Org. Chem. 2018, 14, 2872–2880, doi:10.3762/bjoc.14.266

• generation Grubbs catalyst (GrI) and M1 indenylidene catalyst (Ind). New complexes were formed by replacing one PCy3 phosphine ligand with the cationic NHC 1–3 (Scheme 1). We considered only the dissociative mechanism of initiation, in agreement with the numerous reports on the initiation of Grubbs catalyst

• [57], but we also considered the possibility of cationic carbene dissociation as the first step of the metathesis catalytic cycle (Scheme 3). The results of the computational study are presented in Table 2 and show that in all cases the energy barriers for the dissociation of phosphine ligand (∆G2

• suggest faster activation than first generation Grubbs catalysts, for which the experimental value of ∆G2 was found at 19.88 kcal/mol [58]. Similarly, in the case of indenylidene complexes (1–3-Ind) the dissociation of phosphine is also preferred over the loss of the cationic carbene. For this series of

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow

• Clémentine Minozzi,
• Jean-Christophe Grenier-Petel,
• Shawn Parisien-Collette and
• Shawn K. Collins

Beilstein J. Org. Chem. 2018, 14, 2730–2736, doi:10.3762/bjoc.14.251

• promote the alcohol→halide conversion using low catalyst loadings of a ruthenium-based catalyst (Ru(bpy)3Cl2, 1 mol %) in the absence of PPh3 as a reductant (Figure 1) [8]. The method possesses numerous advantages (wide functional group tolerance, no formation of oxidized phosphine byproducts [9][10][11

• heteroleptic copper(I)-based complexes for photocatalysis. Evaluation of the library of copper-based complexes in photocatalytic alcohol→bromide conversion. Reactions irradiated with 394 nm light (pink) or 450 nm (blue). Front entries without an indicated phosphine ligand pertain to homoleptic Cu(diamine)2BF4

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• (OMe) in DMA at 70 °C. Employing [RhCl(coe)]2 (coe = cyclooctene) and P(Mes)3 ((P(Mes)3 = tris(2,4,6-trimethylphenyl)phosphine) as the catalyst, the carboxylated product 30a was obtained in 67% yield, along with the formation of a methylated byproduct 31a. Other phosphine ligands such as PPh3, P(t-Bu)3

• . reported that a Rh complex with a suitable bidentate ligand was an efficient catalyst for the [2 + 2 + 2] cycloaddition reaction (Scheme 39) [79]. The reaction of 43a was performed using 20 mol % [Rh(cod)2]BF4 and a bidentate phosphine in 1,2-dichloroethane at room temperature. Prior to the addition of 43a

• , the mixture of [Rh(cod)2]BF4 and phosphine was stirred for 30 min. Then, 43a was added dropwise to the mixture over 10 min, and the resulting reaction mixture was further stirred for 16 h. As ligands, SEGPHOS, BIPHEP, and DPPF were ineffective, but BINAP and H8-BINAP afforded the product 44a in

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• ; crystal structures; homeomorphic isomerization; hydrogenation; in/out isomers; metathesis; phosphine boranes; Introduction We have found that a variety of metal complexes with trans-phosphine ligands of the formula P((CH2)mCH=CH2)3 (1; m = 4–14) undergo threefold interligand ring closing alkene

• . Oxidations that lead to the corresponding dibridgehead diphosphine dioxides (O=)P((CH2)n)3P(=O) have exhibited promise, but purification has been problematic [24]. Indeed, phosphine oxides are everyday precursors to phosphines, so we have considered various non-metal-templated routes to 2·2(=O), 3·2(=O), and

• phosphine boranes of alkene containing phosphines. The first involves the monophosphorus precursor H3B·P((CH2)6CH=CH2)3 (1·BH3) [31], and the second a diphosphorus precursor in which one of the methylene chains linking the two phosphorus atoms has already been installed. The advantages and limitations of

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• (Scheme 18a,b) [61]. The addition of indoles to vinylsilanes also succeeded in a similar manner [62]. When styrenes were employed for the hydroarylation with imines 9, the reaction required 4.0 equiv of 2-methoxypyridine as the additive in the presence of CoBr2, [bis(2,4-dimethoxyphenyl)(phenyl)phosphine

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• ][12]. The standard Mitsunobu reaction involves coupling of an alcohol and a nucleophile in a dehydrative SN2 process activated by a reactive combination of a triaryl- or trialkylphosphine as reducing agent and a dialkyl azodicarboxylate as oxidant. In a redox process, the phosphine species is oxidized

• to the respective phosphine oxide and the azo reagent is reduced to the corresponding 1,2-hydrazinodicarboxylate (Scheme 1). As we have frequently utilized this valuable reaction in carbohydrate chemistry, in this account we have compiled literature, where the Mitsunobu reaction was used for the

• phosphine reagents are triphenyl- (Ph3P) or tributylphosphine (n-Bu3P). In recent years, advances have been made using solid supported reagents, thus facilitating work-up conditions [17][18]. The polarity of the commonly aprotic solvents used in the Mitsunobu reaction, including toluene, tetrahydrofuran or

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

• reductive elimination. Starting from the ortho-N-(acyl)diaryl-λ3-iodanes 57, a combination of copper and palladium catalysis, in the presence of a phosphine ligand, induces the internal O-arylation of the proximal amide moiety, followed by a subsequent metal-catalyzed coupling-reaction with the resulting Ar

• cyclic diaryl-λ3-iodanes (Scheme 26) [66]. The palladium phosphine ligand plays a crucial role as a bidentate ligand with a bite angle greater than 100° such as DPEphos (104°) or Xantphos (108°) significantly improves the yields. The reaction applies to a series of anilines and aliphatic amines, but

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• enantiomerically pure (S)-(2-diphenylthiophosphinoferrocenyl)methanol. Deprotection of the thiophosphine unit(s) by tris(dimethylamino)phosphine gave chiral calixarene phosphines 27–29 bearing ferrocenyl substituents on the lower rim in high yields. Calixarene-derived mono(ferrocenylphosphine) ligands 27 and 28

• reactions were compared to that of the model diphenylphosphino ferrocenes. When the allylpalladium chloride dimer was used as palladium precursor, good yields were obtained after 24 h. However, enantiomeric excesses for (S)-27 and (S)-28 (<5%) were lower than those obtained by using other phosphine-ether

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• a carbon–carbon bond-forming reaction occurring between the α-position of an activated alkene and a carbon electrophile such as an aldehyde. Employing a nucleophilic organocatalyst [26], such as a tertiary amine or a phosphine, this simple reaction provides densely functionalized products, such as α

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• via the oxaphosphetane 92 intermediate by treating 4,5-benzotropone (11) with (diphenylmethylene)(phenyl)phosphine oxide (91) generated thermally or photochemically from 90 [82]. Furthermore, dimeric byproduct 93 is also formed under photochemical conditions. 2.2.2. Ring expansion reactions via a

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• derivative of iodosodilactone 6-(3,5-bis(trifluoromethyl)phenyl)-1H,4H-2aλ3-ioda-2,3-dioxacyclopenta[hi]indene-1,4-dione (abbreviated as FPID, Figure 1) [29]. In combination with tris(4-methoxyphenyl)phosphine [(4-MeOC6H4)3P], FPID can efficiently mediate peptide coupling reactions within 30 minutes to

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• , the 3'-amine was protected with an azidomethyloxycarbonyl (Azoc) protecting group. This protecting group can be rapidly removed under non-denaturing conditions after incorporation by the complementary nucleotide using the Staudinger reaction with a water-soluble phosphine (Figure 11). This protocol

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• fluoroalkylated pyruvates is shown with dimethylzinc as a methylating reagent in the presence of a copper catalyst bearing a chiral phosphine ligand. This is the first catalytic asymmetric methylation to synthesize various α-fluoroalkylated tertiary alcohols with CF3, CF2H, CF2Br, and n-CnF2n+1 (n = 2, 3, 8

• ) groups in good-to-high yields and enantioselectivities. Axial backbones and substituents on phosphorus atoms of chiral phosphine ligands critically influence the enantioselectivity. Moreover, the methylation of simple perfluoroalkylated ketones is found to be facilitated by only chiral phosphines without

• copper. Keywords: asymmetric methylation; chiral phosphine ligand; copper catalyst; dimethylzinc; trifluoropyruvate; Introduction The introduction of fluorine atoms into organic compounds plays an important role in the discovery of lead candidates with unique biological and physicochemical properties