Asymmetric Allylic Dearomatization Reaction Research Articles

Pd-Catalyzed intermolecular asymmetric allylic dearomatization of 1-nitro-2-naphthols with MBH adducts.

An asymmetric allylic dearomatization reaction of 1-nitro-2-naphthol derivatives with Morita-Baylis-Hillman (MBH) adducts has been developed. By utilizing Pd catalyst derived from Pd(OAc)2 and Trost ligand (R,R)-L1, the reaction proceeded smoothly in 1,4-dioxane at room temperature, affording substituted β-naphthalenones in good yields (up to 92%) and enantioselectivity (up to 90% ee). A range of substituted 1-nitro-2-naphthols and MBH adducts were found to be compatible under the optimized conditions. This reaction provides a convenient method for the synthesis of enantioenriched 1-nitro-β-naphthalenone derivatives.

Dearomative [4 + 2] Cycloaddition of Pyridine via Energy-Transfer Catalysis

In this issue of Chem, Glorius and coworkers report the first photocatalytic dearomative cycloaddition of pyridine with alkene. High-value isoquinuclidines could be easily assembled from N-cinamoyl picolinamides under mild and operationally simple conditions. In this issue of Chem, Glorius and coworkers report the first photocatalytic dearomative cycloaddition of pyridine with alkene. High-value isoquinuclidines could be easily assembled from N-cinamoyl picolinamides under mild and operationally simple conditions. It seemed too good to be true that complex isoquinuclidines could be directly assembled from simple pyridines and alkenes via [4 + 2] cycloaddition. With the ever-increasing demand for the exploration of chemical space, the rapid construction of this type of complex molecule with a well-defined three-dimensional structure from feedstock chemicals has become an urgent need and a major driving force in the synthetic community. The recent development of visible-light-induced energy-transfer catalysis, as depicted in Scheme 1, has enabled a major breakthrough in the dearomative cyclization of pyridine. As just reported in this issue of Chem by the Glorius group, a photocatalytic [4 + 2] cycloaddition that transfers N-cinnamoyl picolinamides into high-value isoquinuclidines under mild and operationally simple conditions has been achieved, elegantly demonstrating the synthetic potential of visible-light photocatalysis in the construction of complex structures.1Ma J. Strieth-Kalthoff F. Dalton T. Freitag M. Schwarz J.L. Bergander K. Daniliuc C. Glorius F. Direct dearomatization of pyridines via an energy-transfer-catalyzed intramolecular [4 + 2] cycloaddition.Chem. 2019; 5: 2854-2864Abstract Full Text Full Text PDF Scopus (49) Google Scholar Nitrogen-containing heterocycles have long been recognized as one of the most privileged structural manifolds in chemical synthesis because of their ubiquitous presence in natural products, approved pharmaceuticals, and preclinical chemical entities.2Vitaku E. Smith D.T. Njardarson J.T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals.J. Med. Chem. 2014; 57: 10257-10274Crossref PubMed Scopus (2909) Google Scholar Among the available synthetic strategies, catalytic dearomatization of aromatic heterocycles, such as indole and pyridine, has emerged as a rather effective and popular approach.3Zheng C. You S.-L. Catalytic asymmetric dearomatization by transition-metal catalysis: a method for transformations of aromatic compounds.Chem. 2016; 1: 830-857Abstract Full Text Full Text PDF Scopus (357) Google Scholar Because of their availability in commercial sources and the modularity of the hexagonal framework, pyridine substrates have drawn significant research attention in this area. Over the last few decades, tremendous progress has been made in dearomative reductions and dearomative nucleophilic addition transformations,4Remy R. Bochet C.G. Arene-alkene cycloaddition.Chem. Rev. 2016; 116: 9816-9849Crossref Scopus (137) Google Scholar including the exciting development of the catalytic asymmetric dearomatization (CADA) of pyridine;5Yang Z.-P. Wu Q.-F. Shao W. You S.-L. Iridium-catalyzed intramolecular asymmetric allylic dearomatization reaction of pyridines, pyrazines, quinolines, and isoquinolines.J. Am. Chem. Soc. 2015; 137: 15899-15906Crossref PubMed Scopus (105) Google Scholar nevertheless, the scope of the complexity of the generated products remains limited to the six-membered ring system. Utilizing pyridine to build up a bicyclic framework would provide intriguing opportunities to synthesize high-value scaffolds such as isoquinuclidine, yet it still remains a formidable challenge. The utilization of light energy for chemical activation not only allows reactions to be conducted under mild and sustainable conditions but also unlocks intriguing reactivity patterns to provide novel approaches for the construction of complex structures.6Strieth-Kalthoff F. James M.J. Teders M. Pitzer L. Glorius F. Energy transfer catalysis mediated by visible light: principles, applications, directions.Chem. Soc. Rev. 2018; 47: 7190-7202Crossref PubMed Google Scholar The combination of photocatalysis and dearomatization has recently emerged as an exciting supplement to traditional strategies. The synthetic potential of this approach was first demonstrated by the Sarlah group in a two-step dearomative functionalization of benzenoid arenes.7Southgate E.H. Pospech J. Fu J. Holycross D.R. Sarlah D. Dearomative dihydroxylation with arenophiles.Nat. Chem. 2016; 8: 922-928Crossref Scopus (104) Google Scholar Elegantly, the You group8Zhu M. Zheng C. Zhang X. You S.-L. Synthesis of cyclobutane-fused angular tetracyclic spiroindolines via visible-light-promoted intramolecular dearomatization of indole derivatives.J. Am. Chem. Soc. 2019; 141: 2636-2644Crossref Scopus (128) Google Scholar and Glorius group9James M.J. Schwarz J.L. Strieth-Kalthoff F. Wibbeling B. Glorius F. Dearomative cascade photocatalysis: divergent synthesis through catalyst selective energy transfer.J. Am. Chem. Soc. 2018; 140: 8624-8628Crossref Scopus (108) Google Scholar,10Strieth-Kalthoff F. Henkel C. Teders M. Kahnt A. Knolle W. Gómez-Suárez A. Dirian K. Alex W. Bergander K. Daniliuc C.G. et al.Discovery of unforeseen energy-transfer-based transformations using a combined screening approach.Chem. 2019; 5: 2183-2194Abstract Full Text Full Text PDF Google Scholar each reported examples of [2 + 2] dearomative cycloadditions by utilizing visible-light energy transfer to activate indoles and naphthalenes for the facile access of strained cyclobutanes. This energy-transfer activation strategy was demonstrated to be rather straightforward and effective in these cases; nonetheless, it has not been applicable for pyridine substrates. Critically, the overall efficiency of energy transfer is correlated with the energy gap between the excited states of the donor (catalyst) and acceptor (substrate). The triplet state of electron-rich aromatics such as indoles and naphthalenes (55–60 kcal/mol) can be easily accessed by visible-light photocatalysts such as Ir(dF(CF3)ppy)2(dtbpy(PF6) (60.8 kcal/mol). However, the triplet energy of pyridines (>70 kcal/mol) is relatively high in comparison with the light energy of blue-light photons (450 nm, 65 kcal/mol); thus, it is inaccessible by most photocatalysts, rendering pyridines energetically challenging substrates in this catalytic manifold. Accordingly, the photocatalytic dearomatization of pyridines has remained largely elusive. To overcome this particular challenge, the Glorius group implemented alkene 1,2-biradical intermediates as an effective avenue to achieve catalytic dearomatization of pyridine, leading to the development of an operationally simple protocol for transferring easily accessible N-cinnamoyl picolinamides into high-value isoquinuclidine products. Utilizing a visible-light-induced energy-transfer strategy, the authors could effectively activate cinnamyl moieties into the triplet state (∼46 kcal/mol), i.e., a highly reactive 1,2-biradical from a synthetic perspective. Through a clever reaction design, the biradical intermediate could undergo subsequent intramolecular cyclization with the pyridine moiety in a stepwise and highly selective manner to produce solely the desired [4 + 2] cycloaddition product. Under ambient reaction conditions, a variety of substitutions on the pyridine and cinnamyl moieties could be well tolerated, and excellent yields and selectivities were obtained across the board, providing rapid access to a diverse array of biologically relevant isoquinuclidines. Moreover, this efficient catalytic dearomatization reaction employed a polymer-immobilized Ir-based photocatalyst, which could be recycled at least ten times without losing its efficiency, showcasing a sustainable and cost-competitive alternative to classic homogeneous catalysis. Significant mechanistic investigations and density functional theory (DFT) computational studies were performed to rationalize the observed reactivity and selectivity. Notably, DFT calculations suggested that the triplet-energy transfer was thermodynamically favored in a comparison of the excited photocatalyst (ET = 60.8 kcal/mol) and cinnamyl moieties (ET = 45.8-46.5 kcal/mol). In this excited triplet intermediate, the α-carbonyl radical underwent a 5-exo-trig cyclization, and the resulting 1,6-biradical intermediate subsequently underwent radical-radical recombination to form bicyclic isoquinuclidines in a highly selective fashion. Regarding the cyclization pattern, it is worth noting that the dearomative [4 + 2] cycloaddition was, according to the DFT calculations, more favored than the [2 + 2] cycloaddition pathway from both the thermodynamic and kinetic points of view. Overall, this study by the Glorius group has provided a straightforward approach for the construction of a synthetically challenging isoquinuclidine scaffold. The use of ubiquitous alkenes and pyridines for rapid complexity construction, good compatibility between commonly occurring functional groups, and the scalability of gram-scale reactions should certainly be embraced by the synthetic community. Moreover, the application of an energy-transfer strategy to enforce challenging dearomative cyclizations will continue to inspire exciting developments in synthetic chemistry. Z.Z. acknowledges financial support from the National Natural Science Foundation of China (21772121 and 21971163). Direct Dearomatization of Pyridines via an Energy-Transfer-Catalyzed Intramolecular [4+2] CycloadditionMa et al.ChemNovember 14, 2019In BriefAn energy-transfer-catalyzed dearomative [4+2] cycloaddition reaction of pyridines is presented herein. Mechanistically, a ground-state alkene is readily promoted to the corresponding triplet excited state. The resultant highly energetic intermediate then undergoes an efficient dearomative cycloaddition to a pyridine moiety, thus yielding an isoquinuclidine analog. The energy transfer process is enabled by a recyclable polymer-immobilized, iridium-based photocatalyst. This work demonstrates the contribution of visible light catalysis toward enabling thermally challenging organic transformations. Full-Text PDF Open Archive

Iridium‐Catalyzed Intramolecular Asymmetric Allylic Dearomatization Reaction of Benzoxazoles, Benzothiazoles, and Benzimidazoles

AbstractAn iridium‐catalyzed intramolecular asymmetric allylic dearomatization reaction of benzoxazoles, benzothiazoles, and benzimidazoles was developed. The reaction was found to be compatible with a wide range of five‐membered‐ring electron‐deficient heteroaromatic compounds and furnished the corresponding dearomatized heterocycles in high yield with excellent enantioselectivity.

Iridium-Catalyzed Intramolecular Asymmetric Allylic Dearomatization Reaction of Benzoxazoles, Benzothiazoles, and Benzimidazoles.

An iridium-catalyzed intramolecular asymmetric allylic dearomatization reaction of benzoxazoles, benzothiazoles, and benzimidazoles was developed. The reaction was found to be compatible with a wide range of five-membered-ring electron-deficient heteroaromatic compounds and furnished the corresponding dearomatized heterocycles in high yield with excellent enantioselectivity.

ChemInform Abstract: Chemo‐, Diastereo‐, and Enantioselective Iridium‐Catalyzed Allylic Intramolecular Dearomatization Reaction of Naphthol Derivatives.

ChemInformVolume 47, Issue 28 Preparative Organic Chemistry ChemInform Abstract: Chemo-, Diastereo-, and Enantioselective Iridium-Catalyzed Allylic Intramolecular Dearomatization Reaction of Naphthol Derivatives. Qiang Cheng, Qiang Cheng State Key Lab. Organomet. Chem., Shanghai Inst. Org. Chem., Chin. Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorYe Wang, Ye Wang State Key Lab. Organomet. Chem., Shanghai Inst. Org. Chem., Chin. Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorShu-Li You, Shu-Li You State Key Lab. Organomet. Chem., Shanghai Inst. Org. Chem., Chin. Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this author Qiang Cheng, Qiang Cheng State Key Lab. Organomet. Chem., Shanghai Inst. Org. Chem., Chin. Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorYe Wang, Ye Wang State Key Lab. Organomet. Chem., Shanghai Inst. Org. Chem., Chin. Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorShu-Li You, Shu-Li You State Key Lab. Organomet. Chem., Shanghai Inst. Org. Chem., Chin. Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this author First published: 23 June 2016 https://doi.org/10.1002/chin.201628031Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume47, Issue28June, 2016 RelatedInformation

Chemo‐, Diastereo‐, and Enantioselective Iridium‐Catalyzed Allylic Intramolecular Dearomatization Reaction of Naphthol Derivatives

AbstractAn iridium‐catalyzed intramolecular asymmetric allylic dearomatization reaction of naphthol derivatives is described. Challenges confronted in this reaction include chemoselectivity between carbon and oxygen atoms as nucleophilic centers, diastereoselectivity when contiguous chiral centers are generated, and enantioselective control for constructing an all‐carbon quaternary stereocenter. In the presence of an iridium catalyst generated from [{Ir(dbcot)Cl}2] (dbcot=dibenzocyclooctatetraene) and a new THQphos (tetrahydroquinolinedinaphthophosphoramidite) ligand, various spironaphthalenones were obtained with up to greater than 95:5 C/O selectivity, greater than 95:5 d.r., and 99 % ee, thus providing a general method for the dearomatization of naphthols.

Chemo-, Diastereo-, and Enantioselective Iridium-Catalyzed Allylic Intramolecular Dearomatization Reaction of Naphthol Derivatives.

An iridium-catalyzed intramolecular asymmetric allylic dearomatization reaction of naphthol derivatives is described. Challenges confronted in this reaction include chemoselectivity between carbon and oxygen atoms as nucleophilic centers, diastereoselectivity when contiguous chiral centers are generated, and enantioselective control for constructing an all-carbon quaternary stereocenter. In the presence of an iridium catalyst generated from [{Ir(dbcot)Cl}2] (dbcot=dibenzocyclooctatetraene) and a new THQphos (tetrahydroquinolinedinaphthophosphoramidite) ligand, various spironaphthalenones were obtained with up to greater than 95:5 C/O selectivity, greater than 95:5 d.r., and 99 % ee, thus providing a general method for the dearomatization of naphthols.

Iridium-Catalyzed Intramolecular Asymmetric Allylic Dearomatization Reaction of Pyridines, Pyrazines, Quinolines, and Isoquinolines.

The first Ir-catalyzed intramolecular asymmetric allylic dearomatization reaction of pyridines, pyrazines, quinolines, and isoquinolines has been developed. Enabled by in situ formed chiral Ir-catalyst, the dearomatized products were isolated in high levels of yield (up to 99% yield) and enantioselectivity (up to 99% ee). It is worth noting that the Me-THQphos ligand is much more efficient than other tested ligands for the dearomatization of pyrazines and certain quinolines. Mechanistic studies of the dearomatization reaction were carried out, and the results suggest the feasibility of an alternative process which features the formation of a quinolinium as the key intermediate. The mechanistic findings render this reaction a yet unknown type in the chemistry of Reissert-type reactions. In addition, the utility of this method was showcased by a large-scale reaction and formal synthesis of (+)-gephyrotoxin.

ChemInform Abstract: Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions.

The first highly diastereo- and enantioselective synthesis of five-membered spiro-2H-pyrroles was achieved using an Ir-catalyzed asymmetric allylic dearomatization reaction. The spiro-2H-pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir-complex K1, derived from [Ir(cod)Cl]2 (cod=1,5-cyclooctadiene) and N-benzhydryl-N-phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo- and enantioselectivities.

Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions

AbstractThe first highly diastereo‐ and enantioselective synthesis of five‐membered spiro‐2H‐pyrroles was achieved using an Ir‐catalyzed asymmetric allylic dearomatization reaction. The spiro‐2H‐pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir‐complex K1, derived from [Ir(cod)Cl]2 (cod=1,5‐cyclooctadiene) and N‐benzhydryl‐N‐phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo‐ and enantioselectivities.

Enantioselective Synthesis of Pyrrole-Based Spiro- and Polycyclic Derivatives by Iridium-Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions.

The first highly diastereo- and enantioselective synthesis of five-membered spiro-2H-pyrroles was achieved using an Ir-catalyzed asymmetric allylic dearomatization reaction. The spiro-2H-pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir-complex K1, derived from [Ir(cod)Cl]2 (cod = 1,5-cyclooctadiene) and N-benzhydryl-N-phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo- and enantioselectivities.

ChemInform Abstract: Direct Asymmetric Dearomatization of Pyridines and Pyrazines by Iridium‐Catalyzed Allylic Amination Reactions.

AbstractThe first iridium‐catalyzed intramolecular asymmetric allylic dearomatization reaction of pyridines and pyrazines is developed.

ChemInform Abstract: Highly Regio and Enantioselective Synthesis of Chiral Polysubstituted 2H‐Pyrroles

AbstractReview: 3 refs.

Mechanistic insights into the Pd-catalyzed intermolecular asymmetric allylic dearomatization of multisubstituted pyrroles: understanding the remarkable regio- and enantioselectivity.

In this article we report a comprehensive density functional theory study on the Pd-catalyzed intermolecular asymmetric allylic dearomatization reactions of multisubstituted pyrroles. The calculated results are in line with the previous experimental observations (J. Am. Chem. Soc. 2014, 136, 6590), and the remarkable regio- and enantioselectivity are well explained. Of all the potential nucleophilic sites around the multisubstituted pyrrole ring, the reaction always occurs at the position where the HOMO of the molecule distributes most significantly. In contrast to the common view on the enantioselectivity of the Pd-catalyzed asymmetric allylic substitution reactions, we find that the steric interaction between the nucleophile and the chiral ligand does not have the dominating effect on the enantioselectivity of the reaction. Instead, the interaction between the allyl moiety and the incoming nucleophile plays an important role in the enantioselectivity-determining process.

Highly regio- and enantioselective synthesis of chiral polysubstituted 2H-pyrroles

As one of the most important five-member heterocyclic aromatic rings, pyrrole is widely distributed in numerous natural products and pharmaceutical agents. Asymmetric dearomatization of pyrroles is very attractive in organic synthesis given the fact that highly functionalized chiral pyrrolines and pyrrolidines could be easily accessed from the readily available pyrroles. However, the reported asymmetric dearomatization reactions of pyrroles are limited to transition-metal-catalyzed [4+3] cycloaddition and hydrogenation reactions. The enantioselective intermolecular alkylative dearomatization of pyrroles is rare and challenging due to multiple selectivity issues including the chemoselectivity (C2&N1), regioselectivity (C2&C4, C2&C5) and enantioselectivity (Scheme 1) [1]. During the past few years, the You group from Shanghai Institute of Organic Chemistry has focused on the transition-metal-catalyzed asymmetric allylic dearomatization reactions [2]. Recently, the researchers in this group found that highly enantioenriched poly-substituted 2H-pyrroles could be easily accessed via Pd-catalyzed intermolecular asymmetric allylic dearomatization reaction of polysubstituted pyrroles (Scheme 1). With the commercially available palladium precursor and chiral ligand, various poly-substituted 2H-pyrrole products containing a chiral quaternary carbon center were obtained with up to 97% ee under mild reaction conditions. Interestingly, they found the reaction occurred smoothly to give good to excellent regioselectivities when tri-substituted and tetra-substituted pyrrole derivatives were used. In addition, chiral pyrrolines and cyclic imines could be conveniently prepared by selective reductions of the enantioenriched 2H-pyrrole products, further demonstrating the synthetic utility of this newly developed method. Moreover, this reaction represents the first example involving the multi-substituted pyrroles as prochiral nucleophiles in Pd-catalyzed asymmetric allylic alkylation reactions.

Transition-metal-catalyzed asymmetric allylic dearomatization reactions.

Dearomatization reactions serve as powerful methods for the synthesis of highly functionalized, three-dimensional structures starting with simple planar aromatic compounds. Among processes of this type, catalytic asymmetric dearomatization (CADA) reactions are attractive owing to the large number of aromatic compounds that are readily available and the fact that they enable direct access to enantiopure polycycles and spirocycles, which frequently are key structural motifs in biologically active natural products and pharmaceuticals. However, as a consequence of their high stabilities, arenes only difficultly participate in dearomatization reactions that take place with high levels of enantioselectivity. Transition-metal-catalyzed asymmetric allylic substitution reactions have been demonstrated to be powerful methods for enantioselective formation of C-C and C-X (X = O, N, S, etc.) bonds. However, the scope of these processes has been explored mainly using soft carbon nucleophiles, some hard carbon nucleophiles such as enolates and preformed organometallic reagents, and heteroatom nucleophiles. Readily accessible aromatic compounds have been only rarely used directly as nucleophiles in these reactions. In this Account, we present the results of studies we have conducted aimed at the development of transition-metal-catalyzed asymmetric allylic dearomatization reactions. By utilizing this general process, we have devised methods for direct dearomatization of indoles, pyrroles, phenols, naphthols, pyridines, and pyrazines, which produce various highly functionalized structural motifs bearing all-carbon quaternary stereogenic centers in a straightforward manner. In mechanistic investigations of the dearomatization process, we found that the five-membered spiroindolenines serve as intermediates, which readily undergo stereospecific allylic migration to form corresponding tetrahydro-1H-carbazoles upon treatment with a catalytic amount of TsOH. It is worth noting that no notable loss of the enantiomeric excess of the spiroindolenine derivatives takes place during the rearrangement process as a consequence of the intervention of a "three-center-two-electron"-type transition state, a proposal that has gained support from the results of DFT calculations. Equally intriguing, upon tuning of the electronic nature of the tethers, pyrroles or indoles undergo unprecedented Ir or Ru catalyzed intramolecular allylic alkylation promoted dearomatization/migration reactions. The operation of this novel reaction pathway provides additional information leading to a greater mechanistic understanding of the transition-metal-catalyzed enantioselective intramolecular functionalizations of pyrroles and indoles. The combined results of this effort provide not only methods for the efficient synthesis of highly enantioenriched fused and spiro polycycles but also novel strategies in the field of asymmetric catalysis.

Direct asymmetric dearomatization of pyridines and pyrazines by iridium-catalyzed allylic amination reactions.

The first iridium-catalyzed intramolecular asymmetric allylic dearomatization reaction of pyridines and pyrazines has been realized. 2,3-Dihydroindolizine and 6,7-dihydropyrrolo[1,2-a]pyrazine derivatives were obtained with excellent yields and enantioselectivity. This methodology features dearomatization by direct N-allylic alkylation of pyridines or pyrazines under mild reaction conditions.

Direct Asymmetric Dearomatization of Pyridines and Pyrazines by Iridium‐Catalyzed Allylic Amination Reactions

AbstractThe first iridium‐catalyzed intramolecular asymmetric allylic dearomatization reaction of pyridines and pyrazines has been realized. 2,3‐Dihydroindolizine and 6,7‐dihydropyrrolo[1,2‐a]pyrazine derivatives were obtained with excellent yields and enantioselectivity. This methodology features dearomatization by direct N‐allylic alkylation of pyridines or pyrazines under mild reaction conditions.

Highly regio- and enantioselective synthesis of polysubstituted 2H-pyrroles via Pd-catalyzed intermolecular asymmetric allylic dearomatization of pyrroles.

A highly efficient synthesis of chiral polysubstituted 2H-pyrrole derivatives via a Pd-catalyzed intermolecular asymmetric allylic dearomatization reaction of pyrroles is presented. With the commercially available palladium precursor and chiral ligand, the polysubstituted 2H-pyrrole products containing a chiral quaternary carbon center were obtained with up to 97% ee and >95/5 regioselectivity.

Ir-catalyzed intermolecular asymmetric allylic dearomatization reaction of indoles

An Ir-catalyzed intermolecular asymmetric dearomatization reaction of substituted indoles with allylic alcohols has been realized to afford the corresponding indoline derivatives in 71–97% yield with up to 98% ee in the presence of the Lewis acid Fe(OTf)2. This methodology features the enantioselective construction of all-carbon quaternary stereogenic centers of prochiral nucleophiles and its utility has been demonstrated in the asymmetric total synthesis of (−)-debromoflustramine B.