Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• alkylpalladium radical with the release of dinitrogen. The radical intermediate selectively adds to the double bond of a 1,3-diene or allene, followed by the allylpalladium radical-polar crossover path and selective allylic substitution with the amine substrate, thereby leading to a single unsaturated γ- or ε

• next turned to evaluate the scope of 1,3-dienes. Although the regioselectivity control of allylic substitution can be attributed to many factors, it is agreed that steric hindrance generally is the primary factor affecting the regioselectivity of nucleophilic attack [54][55][56][57]. Monoalkyl

• allenes that were never used as substrates in interrupted radical Heck/allylic substitution reactions. As summarized in Scheme 3, unsaturated γ-AA derivatives were observed in this reaction albeit with poor stereoselectivity. Linear amines containing alkyl, hydroxy, and terminal alkenyl groups were

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• Toulouse, France University of Tunis El Manar, Laboratory of Organic Chemistry, Faculty of Sciences, Campus, 2092 Tunis, Tunisia 10.3762/bjoc.19.93 Abstract A highly α-regioselective N-nucleophilic allylic substitution of cyclic MBH alcohols and acetates with imidazole or benzimidazole, in toluene at

• performed using DABCO as an additive, leading to the corresponding 1,4-adducts in 70–84% yields. Keywords: allylic substitution; aza-Michael addition; imidazole; Morita–Baylis–Hillman; Introduction Morita–Baylis–Hillman (MBH) adducts are multifunctionalized compounds having both a hydroxy moiety and a

• Michael acceptor unit. They have found application as valuable synthons and useful precursors for the synthesis of various biologically active molecules [1][2][3]. Recently, MBH adducts, as electrophilic substrates, have been employed to achieve fruitful results in allylic substitution reactions with

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• stereochemistry in the Ir-catalyzed allylic substitution reactions. In 2016, Billingsley and co-workers disclosed the total synthesis of (−)-indolactam V (6), a nanomolar agonist of protein kinase C (Scheme 3) [12]. The authors applied an intramolecular SEAr reaction of 4-substituted indole derivative to

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

• would be significant in many fields [4][5][6][7]. Although transition-mental-catalyzed allylic substitution reactions employing various nucleophilic or electrophilic allylic precursors have been extensively studied [8][9][10], limited strategies were reported for their application in the C(sp3)–H

• pyridylic C(sp3)–H bond (Scheme 1b). For examples, Tunge et al. developed a Pd-catalyzed intramolecular decarboxylative coupling of heterocyclic ally esters via a tandem allylation/Cope rearrangement strategy [18]; Hartwig and co-workers reported a stereo-divergent allylic substitution with azaarene

• acetamides and acetates catalyzed synergistically by a metal acyclic iridium complex and a chiral Cu(I) complex [19]. Besides transition-metal-catalyzed allylic substitution reactions, Lewis-base-catalyzed allylic functionalizations using Morita−Baylis−Hillman (MBH) adducts as electrophilic allylic

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• -workers exploited the copper-catalysed asymmetric ring opening of polycyclic meso hydrazines with organoaluminium reagents (Scheme 13) [43]. This reaction followed a classical allylic substitution pathway. Interestingly, the organoaluminium reagents in this reaction did not only act as alkyl donors but

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• -catalyzed allylic substitution. Keywords: aldehyde; copper; copper catalysis; cross-coupling; palladium; synthetic method; Introduction α-Alkoxy-substituted carbanions (α-alkoxyalkyl anions) are useful C(sp3) nucleophiles for the construction of alcohol units found in a majority of pharmaceuticals

• alcohol derivatives. This process involves the catalytic formation of a nucleophilic α-silyloxybenzylcopper(I) species and the subsequent palladium-catalyzed allylic substitution. Experimental SIPrCuCl (14.7 mg, 0.03 mmol), and KOt-Bu (4.5 mg, 0.04 mmol) were placed in a vial containing a magnetic

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• trifluoromethylated benzaldehyde was accomplished as described for compound 2 and furnished product 6 in 91% yield. The Alloc-protecting group was then cleaved (95% yield of product 8) in a palladium-catalyzed allylic substitution reaction with morpholine as a scavenger of the allylic cation [45][46]. Finally, the

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• efficient catalysts in various asymmetric reactions, for instance allylic substitution and enantioselective hydrogenation [9]. They were also applied in the stereoselective synthesis of complex natural products [10][11][12]. PHOX ligands are nonsymmetrical ligands which can coordinate to a metal center

• through their N- and P-moieties. They are usually prepared from amino acids or from the corresponding amino alcohols [9][13]. Some examples of literature-known PHOX ligands are shown in Figure 1 (1a–d). These ligands gave up to 96% ee by their application in allylic substitution with dimethyl malonate as

• -glucosamine and the sugar was linked to the aromatic system via an annulated oxazoline. Palladium complexes of 2 were used in allylic substitution of allyl acetates with dimethyl malonate as nucleophile and ee values from 69% to 98% were obtained [19]. Recently, we presented the synthesis of carbohydrate

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

• reaction in the following order: phase-transfer catalysis, Henry reaction, Suzuki–Miyaura cross-coupling and Tsuji–Trost allylic substitution, hydrogenation, Michael addition, aldol and multicomponent Biginelli reactions, epoxidation, Meerwein−Ponndorf−Verley reduction, aza-Diels−Alder and epoxide ring

• . The low enantioselectivities obtained were mainly attributed to the high flexibility of catalytic amino groups of N,O-type enantiomers. Suzuki–Miyaura cross–coupling and Tsuji–Trost allylic substitution reaction Manoury et al. described the synthesis of ferrocene-bearing enantiomerically pure

• important transformations: phase-transfer catalysis, Henry reaction, Suzuki–Miyaura cross-coupling and Tsuji–Trost allylic substitution, hydrogenation, Michael addition, aldol and multicomponent Biginelli reactions, epoxidation, Meerwein–Ponndorf–Verley reduction, aza-Diels–Alder and epoxide ring-opening

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• corresponding SN2-type products 6a–d in 63 to 70% isolated yields. Alternatively, the alcohol 5 produced the corresponding acetate 7 which, mediated by Ce(III), was successfully converted into the corresponding γ-aminoallylphosphonates 8a–d. Keywords: allylic substitution; γ-aminoallylphosphonate; Arbuzov

• , without any additive, provided, after thermal Arbuzov rearrangement, a variety of diethyl allylphosphonates (Scheme 1, reaction 3) [18]. Moreover, the asymmetric allylic substitution of MBH carbonates with diphenyl phosphonate using chiral thiourea phosphite as catalyst, afforded the related

• allylphosphonates (Scheme 1, reaction 4) [19]. We have previously reported a direct nucleophilic allylic substitution of cyclic MBH alcohols by β-dicarbonyl compounds [20]. In addition, in our recent work [21], we have described an efficient protocol for the synthesis of a new series of allylphosphonates in high

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• -dicarbonyl compounds with both cyclic and acyclic Morita–Baylis–Hillman (MBH) alcohols, using Et3B as a Lewis acid promoter, is described herein. A wide range of the corresponding functionalized allylated derivatives have been obtained in good yields and with high selectivity. Keywords: allylic substitution

• Tsuji–Trost reaction involving, as substrates, allyl carboxylates [2], carbonates [3], and phosphates [4]. Obviously, the direct nucleophilic allylic substitution of allyl alcohols is a more attractive process especially from an economical and environmental point of view [5], as water, generated by this

• ], which further gives, in the presence of Pd(0), the π-allylpalladium complex I2. This intermediate reacts then with the diethyl malonate carbanion I3, in situ formed, to generate the promoter Et3B of this nucleophilic allylic substitution and the desired allylated product 3a. Next, under the previously

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• ligands were tested in the iridium-catalyzed asymmetric hydrogenation and palladium-catalyzed allylic substitution. In both reactions high enantioselectivities were achieved, that were comparable to the enantioselectivities obtained with the up to now best NeoPHOX ligand derived from expensive tert

• -leucine. Keywords: allylic substitution; asymmetric hydrogenation; iridium; N,P ligand; palladium; Introduction Since their introduction and first successful application in enantioselective palladium-catalyzed allylic substitution in 1993 [1][2][3], chiral phosphinooxazolines (PHOX ligands) have emerged

• coordination to the iridium center. Palladium-catalyzed allylic substitution As phosphinooxazoline ligands were originally designed for asymmetric palladium-catalyzed allylic substitutions, we tested the new NeoPHOX ligands in this reaction as well. For comparison with state-of-the-art ligands, we chose the

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• ] cycloaddition to form a ruthenacyclobutane, and reductively eliminates to generate the bicyclic product. Intrigued by the possibility of rendering this reaction asymmetric, we wondered if an appropriate choice of catalyst, namely the chiral CpRu-sulfoxide catalysts 1 our group developed for asymmetric allylic

• substitution reactions [42] (Figure 1b), would be able to impart sufficiently useful enantioselectivities on these complex, drug-like molecules. While the idea certainly was appealing at first glance, this reaction is complicated by the fact that the 1,6- and 1,7-enyne substrates contain a stereogenic center

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• , Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany 10.3762/bjoc.12.107 Abstract The design, development and application of an efficient procedure for the concise synthesis of the 1,3-syn- and anti-tetrahydropyrimidine cores of manzacidins are reported. The intramolecular allylic substitution reaction of a

• allylic substitution reaction of a joint precursor 5. Subsequently this strategy is successfully applied to the synthesis of the authentic pyrimidine cores 3 and 4 of manzacidin A (1) and ent-manzacidin C (2). Results and Discussion General synthetic concept As part of our ongoing efforts to the design of

• groups [38][39][40][41][42][43], is based on a sequential nucleophilic addition and an intramolecular allylic substitution reaction. It relies on the coupling of different homoallylic nucleophiles of general type 6 to diverse electrophiles 7 such as Michael acceptors, or heteroolefins as for example

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• of thiazol-4(5H)-ones as pronucleophiles in asymmetric catalytic reactions has been investigated in the Michael addition reaction to nitroalkenes and α-silyloxyenones, phosphine-catalyzed γ-addition to allenoates and alkynoates, α-amination reactions and iridium-catalyzed allylic substitution

• bearing the quinoyl moiety provided once again better stereochemical results than 2-naphthylthiazolones. 2.2.3 Iridium-catalyzed allylic substitution reactions. Allylic substitution reactions catalyzed by cyclometalated iridium phosphoramidite complexes constitute a powerful tool for the construction of C

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• ligands were active precatalysts for the allylic substitution, as can be seen in Table 1. The asymmetric allylic alkylation was carried out in the presence of 5 mol % [PdCl(C3H5)]2 and 11 mol % chiral ligands 9 and 10, respectively. The D-fructo-configurated ligands 9a and 9b showed preparative yields for

• )-14 of 9% (Table 1, entry 11). The stereoselectivity of the Pd-catalyzed allylic substitution can be explained via a model for the proposed transition state (Scheme 4). As a consequence of the spiro-fused carbohydrate moiety at the oxazoline ring, exo (15x and 17x) and endo (15n and 17n) diastereomers

• ]. Therefore, four reaction pathways are possible, but only two lead to the observed stereoselectivties. We assume, that the nucleophilic attack occurs at the allyl terminus trans to the oxazoline ring, which is in accordance with previously reported findings in allylic substitution using PyOx ligands [32][33

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• for the formation of carbon–carbon and carbon–heteroatom bonds as well as the asymmetric allylic substitution with a wide range of nucleophiles for the formation of C–C and carbon–heteroatom bonds. Review Copper-catalyzed coupling of aryl halides with nucleophiles Chiral auxiliary-induced aryl C–C

• ). Copper-catalyzed couplings of allylic halides with nucleophiles Transition metal-catalyzed allylic substitutions are the most important process for carbon–carbon and carbon–heteroatom bond formation in organic synthesis [56][57][58]. Allylic substitution of the substrate with nucleophiles can afford two

• other metals (Pd, Mo, and Ir), copper-catalyzed allylic substitution reactions allow the use of nonstabilized nucleophiles including organomagnesium, organoaluminum, organozinc and organoborane reagents. Moreover, copper-catalyzed allylic substitution reactions usually proceed with high SN2

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• developments in nucleophilic chiral phosphine-catalyzed asymmetric reactions, including annulations of allenes, ketenes, alkynes, and Morita–Baylis–Hillman (MBH) carbonates with activated alkenes and imines, allylic substitution of MBH acetates and carbonates, Michael additions, γ-umpolung additions, and

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• ][38][39][40] or Pd0-allylic substitution [42][43] of alkenols having an allylic OR group and additional halocyclisation. Conclusion In summary, we have developed the syntheses of several unsaturated alcohols. The chiral alkenols 20–28, 34–37 and 43 represent useful C5–C12 chain building blocks. The

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• range of substrates. Keywords: allylic substitution; enantioselectivity; ferrocene; organophosphorus; palladium; regioselectivity; Introduction The palladium-catalyzed asymmetric allylic alkylation (AAA) reaction is now becoming an efficient method for the construction of carbon–carbon bonds [1][2][3

• ][4][5]. Despite extensive investigation and noteworthy advances in this field, several challenges remain to be solved. For instance, with monosubstituted allyl substrates, the palladium-catalyzed allylic substitution reaction prefers to give linear products rather than the branched ones [6][7][8][9

• ] (Scheme 1). Accordingly, the regio- and enantioselective allylic substitution reaction of monosubstituted allylic substrates to preferably obtain the branched products is one of the continuing challenges. To our knowledge, there are several cases in which high levels of both regio- and enantioselectivity

Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed annulation with diarylethynes

• Yan-Chao Shi,
• Rong-Fei Yang,
• De-Wei Gao and
• Shu-Li You

Beilstein J. Org. Chem. 2013, 9, 1891–1896, doi:10.3762/bjoc.9.222

• ). The allylic substitution reactions of (rac)-4 had been carried out. The allylic alkylation reaction proceeded in 95% yield and 44% ee (Scheme 3, reaction 1) and the allylic amination reaction proceeded in 32% yield and 43% ee (Scheme 3, reaction 2) [69][70][71]. Although only moderate

• could be transformed readily into a P,N-ligand, which was found to be suitable for Pd-catalyzed allylic substitution reactions. Experimental General procedure for the enantioselective synthesis of planar chiral ferrocenes To a solution of alkyne 2 (0.46 mmol) in DMA (1.5 mL) was added Boc-L-Val-OH (8.7

Chiral multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman carbonates with maleimides

• Hong-Ping Deng,
• De Wang,
• Yin Wei and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 1098–1104, doi:10.3762/bjoc.8.121

• was shown that chiral multifunctional thiourea-phosphines were excellent catalysts for the asymmetric aza-MBH reaction, asymmetric allylic substitution of MBH adducts, and asymmetric [3 + 2] annulation of MBH carbonates with electron-deficient olefins [52][53][54][55][56]. Hence, we initially used

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• and enones, as well as in palladium-catalyzed allylic substitution reactions [14][15][16][17][18][19][20]. Thus, the synthesis of specifically functionalized pyridines is of considerable interest, and many approaches toward this heterocyclic structure have been disclosed in the literature [21]. In

Palladium-catalyzed formation of oxazolidinones from biscarbamates: a mechanistic study

• Benan Kilbas and
• Metin Balci

Beilstein J. Org. Chem. 2011, 7, 246–253, doi:10.3762/bjoc.7.33

• -withdrawing groups will enhance the stability of the complex [25][26]. The next step is the ionization step followed by allylic substitution. The final step is the decomplexation. Trost et al. [3] and Fiaud et al. [6] have proposed that only metal–olefin complexation anti to the leaving group will lead to the

Ene–yne cross-metathesis with ruthenium carbene catalysts

• Cédric Fischmeister and
• Christian Bruneau

Beilstein J. Org. Chem. 2011, 7, 156–166, doi:10.3762/bjoc.7.22

• transformations in the presence of ruthenium catalysts, which are able to perform regioselective allylic substitution by O-, N- and C-nucleophiles (Scheme 8a) [55] and elimination to provide a new access to dendralenes (Scheme 8b) [56]. Higher olefin–alkyne cross-metathesis This cross-metathesis reaction was