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

• ,b from the reaction of chiral NHC precursors based on a phenoxyimine-imidazolium motif with Cu2O in THF in >90% yield. The reaction solvent was found to be important; in dichloromethane, interactable products were formed in contrast to the excellent yields obtained in THF. Furthermore, the NHC–CuBr

• enantioselectivity, using NHC–Cu(I) complexes generated in situ from chiral imidazolium salts containing possible chelating functional group(s). For example, the conjugate addition of Grignard reagents to 3-methyl- and 3-ethylcyclohexenones in the presence of the C2-symmetric chiral NHC–copper complex catalyst

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

• 10.3762/bjoc.19.65 Abstract We present here a stereoselective tandem reaction based on the asymmetric conjugate addition of dialkylzinc reagents to unsaturated acylimidazoles followed by trapping of the intermediate zinc enolate with carbocations. The use of a chiral NHC ligand provides chiral zinc

• . Results and Discussion For initial experiments, we have selected the conjugate addition of Me2Zn to acylimidazole 1a catalyzed by a chiral NHC ligand derived from imidazolium salt L1. This NHC precursor has been described previously by Gérard, Mauduit, Campagne and co-workers [19]. The ligand L1 is

• chiral NHC ligand L1 (3.36 mg, 0.0075 mmol, 3 mol %) were dissolved in freshly distilled anhydrous THF (1.0 mL) and the mixture was stirred for 10 min at rt. The reaction mixture was cooled to 0 °C, and then 1.6 M n-BuLi (12.5 µL, 0.02 mmol, 8 mol %) was added dropwise and the mixture was stirred for 10

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

• pyridine 195 and C4 pyridine 197 can undergo endo-cyclization reactions in the presence of Ni(cod)2, a chiral NHC ligand, and MAD as Lewis acid to afford optically active 5,6,7,8-tetrahydroquinolines 194 and 5,6,7,8-tetrahydroisoquinolines 196 and 198. The endo-selective annulation approach was compatible

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• reported in a work Shi and co-workers in 2008 who studied the addition of arylboronic acids to 2-cyclohexenone catalysed by Pd complexes of axially chiral NHC carbenes with two other weakly coordinating ligands [44][45]. The complexes with acetates (PdL7a), trifluoroacetates (PdL7b), and diaquo complex

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• . Another example was reported by Rovis in 2013 using enal 108 in the presence of chiral NHC 109 to form extended Breslow intermediate 110 (Scheme 14) [52]. Photoisomerisation of 110 is then required for the following spirocyclisation reaction to intermediate 111 to proceed, which then releases the NHC

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• that α-amino esters could be obtained in excellent chemical yields with little erosion in enantiopurity. Similar work was described by Zhao et al. using a C1-symmetric chiral NHC ligand L6 together with catalytic amounts of CuCl. Here again, reactions could be performed on numerous albeit activated

• products (e.g., 316) yielded nonracemic secondary (e.g., 317) and tertiary alcohols (e.g., 319). The presence of Cu(OTf)2, an imidazolium salt, and NaOMe leads to a chiral NHC–Cu complex, which, in the presence of B2pin2, generates the corresponding B–Cu species followed by its addition to allylic

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• , Sapporo, Hokkaido 001-0021, Japan 10.3762/bjoc.16.50 Abstract A chiral phenol–NHC ligand enabled the copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters. The phenol moiety of the chiral NHC ligand played a critical role in producing the enantiomerically enriched products. The

• catalyst worked well for various (Z)-isomer substrates. Opposite enantiomers were obtained from (Z)- and (E)-isomers, with a higher enantiomeric excess from the (Z)-isomer. Keywords: catalyst; chiral NHC; conjugate reduction; copper catalysis; enantioselective reaction; Introduction Since the leading

• Optimization The initial investigation of the reaction conditions was carried out with ethyl (Z)-3-phenylbut-2-enoate (1a) as a substrate (Table 1). When chiral NHC precursor L1·HBF4 (10 mol %) was used in combination with CuCl (10 mol %) and LiOt-Bu (20 mol %) for the conjugate reduction of 1a with

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• -catalyzed conjugate addition of alkyl boranes to α,β-unsaturated 2-acyl-1-methylbenzimidazoles 33 [36]. Based on a previous study dealing with the CuCl/IMes-catalyzed addition of various alkylated 9BBN derivatives [37], the authors screened a set of various chiral NHC precursors. The imidazolium compound

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

• rearrangement and then successfully trapped with aryl bromides under palladium catalysis (Scheme 1). This system was extended to an asymmetric version using the chiral α-silyloxybenzylcopper(I) species having a chiral NHC ligand. In the asymmetric system, one example of allylic carbonate was used as the carbon

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

• loading of 0.125 mol %. In 2008, Blechert and Buchmeiser et al. introduced a ruthenium complex featuring an unsymmetrical, chiral NHC ligand 44 and its pyridine derivative 45 (Figure 12) [26]. Both complexes revealed as efficient systems to promote the alternating copolymerization of norbornene (NBE, 46

• ) [62]. These complexes were tested in model ARCM of trienes 166 and 199 showing moderate enantioselectivities (14–44% ee). Ruthenium catalysts coordinated with backbone monosubstituted N-aryl, N’-aryl NHCs In 2010, Blechert and co-workers synthesized a new type of chiral NHC ruthenium catalysts

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• ][7]. Some additional recent examples are discussed below. A selected list of chiral NHC catalysts that have been explored for mediating asymmetric benzoin reactions is presented in Scheme 5. The bis-triazolium catalyst 9 developed by You promoted asymmetric benzoin reactions in 95% ee [13]. Enders

• yields (Scheme 14). Interestingly, preliminary experiments to develop an enantioselective version of this reaction using a chiral NHC returned promising levels of enantioselectivity (76% ee). Subsequently, Gravel and co-workers reported a high yielding chemoselective and enantioselective intermolecular

• chiral NHC-catalysts used for asymmetric homobenzoin condensation. A rigid bicyclic triazole precatalyst 15 in an efficient enantioselective benzoin reaction. Inoue’s report of cross-benzoin reactions. Cross-benzoin reactions catalysed by thiazolium salt 17. Catalyst-controlled divergence in cross

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• variety of unsymmetrical NHC precursors [25]. With this new methodology in hand, Mauduit and co-workers synthesized several bidentate chiral NHC precursors, using amino acids and amino alcohols as starting materials, and tested them in copper-catalyzed ACA [26]. Leucine-based L5 displayed the best

• [32]. When the catalytic system was formed in situ from chiral NHC-based L11 and (CuOTf)2·C6H6, a large library of substrates was tested, and good yields and ees were consistently observed. Among the Michael acceptors that were submitted to the reaction conditions, cyclic enynone 46 selectively led to

• . Copper-catalyzed conjugate addition of trimethylaluminium onto nitro dienoates. Copper-catalyzed selective 1,4-ACA in total synthesis of erogorgiaene. 1,4-selective addition of diethylzinc onto a cyclic enynone catalyzed by a chiral NHC-based system. Cu-NHC-catalyzed 1,6-ACA of dimethylzinc onto an α,β,γ

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• retained the properties of stability and recyclability. In 2002, Hoveyda et al. reported the Hoveyda–Grubbs’ 2nd generation type catalyst 36 (Figure 3) [56]: Complex 36, bearing an unsymmetrical and chiral NHC, was active in the asymmetric ring-opening cross-metathesis (RO/CM) in air using undistilled

Synthesis of axially chiral gold complexes and their applications in asymmetric catalyses

• Yin-wei Sun,
• Qin Xu and
• Min Shi

Beilstein J. Org. Chem. 2013, 9, 2224–2232, doi:10.3762/bjoc.9.261

• . However, chiral gold complexes [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45], especially chiral NHC–gold complex-catalyzed asymmetric reactions [46][47][48][49][50][51][52][53] are still uncommon. Very few efficient chiral NHC–gold catalysts have been known up to the year of 2013. So

• far, several axially chiral NHC–gold catalysts based on binaphthyl skeleton such as 1 and 2 [46][49] have been reported with good to excellent chiral inductions in asymmetric gold catalysis (Figure 1). Encouraged by these results, we attempted to develop novel types of axially chiral NHC–gold

• , 128.42, 127.1, 126.6, 126.42, 126.39, 126.2, 58.3, 55.4, 52.2, 45.9, 22.1, 21.4; [α]D20 20.1 (c 1.2, CH2Cl2), for 29% ee; Chiralcel PA-2, hexane/iPrOH = 60/40, 0.5 mL/min, 214 nm, tmajor = 45.07 min, tminor = 27.49 min. Monodentate chiral NHC gold catalysts in recent years. The crystal data of gold

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• stability of their metal complexes, and the convenient introduction of chiral elements, have also emerged as effective ligands for a number of homogeneous gold catalyzes [1][2][3][4][5][6][7][8]. However, during our ongoing survey of chiral NHC–Au(I) complexes in the literature, we only found a few unique

• papers of relevance. Tomioka and co-workers disclosed the first chiral NHC–Au(I) complex 1 (Figure 1), which was applied to catalyze the asymmetric cyclization of 1,6-enynes giving the corresponding cyclopentane derivatives with moderate enantioselectivity up to 59% [9][10]. Iglesias and co-workers

• chiral NHC–Au(I) complexes (4–6) with a binaphthyl or biphenyl framework [13][14]. These Au(I) complexes were applied to catalyze the asymmetric cyclization of 1,6-enynes or allene in up to 70% ee, and the asymmetric intramolecular hydroamination of allene in up to 44% ee. We previously reported a novel

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

Synthesis of chiral mono(N-heterocyclic carbene) palladium and gold complexes with a 1,1'-biphenyl scaffold and their applications in catalysis

• Lian-jun Liu,
• Feijun Wang,
• Wenfeng Wang,
• Mei-xin Zhao and
• Min Shi

Beilstein J. Org. Chem. 2011, 7, 555–564, doi:10.3762/bjoc.7.64

• complex 2 with a biaryl framework, in which one of biaryl groups bearing a substituent might provide steric hindrance to limit the rotation of the N–Ar bond. Herein we wish to report the synthesis of novel chiral [(NHC)Pd(allyl)I] and mono(NHC)–Au complexes bearing an axially chiral biphenyl framework

• (Me) 2 on heating in THF for 8 h in the presence of KI and t-BuOK to give the expected chiral NHC–Au(I) complex (S)-6a in 65% yield (Scheme 3). Its structure was also confirmed by X-ray diffraction (Figure 4) [56]. It was found that the Au–carbene distance is 2.036 Å which is consistent with other

• salt (S)-5b in quantitative yield. Benzimidazolium salt (S)-5b was then complexed with Au (I) as described above for (S)-6a (AuCl·S(Me)2 in the presence of KI and t-BuOK in THF for 8 h) to produce the expected chiral NHC–Au(I) complex (S)-6b in 32% yield. For the preparation of (S)-6c, (S)-6,6

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• . The asymmetric transannular aldol reaction catalysed by trans-4-fluoroproline (41), and its application to the total synthesis of (+)-hirsutene (46). The asymmetric Stetter reaction catalysed by chiral NHC catalysts 49–52. The ring conformations of 50–52 are influenced by σCH→σ*CF hyperconjugation. Cy