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Victor Snieckus - One of the best experts on this subject based on the ideXlab platform.
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regioselective functionalization of 7 azaindole by controlled annular isomerism the directed Metalation group dance
Angewandte Chemie, 2019Co-Authors: Michael E Dalziel, Jignesh J Patel, Meagan K Kaye, Jennifer L Cosman, Matthew O Kitching, Victor SnieckusAbstract:The regioselective functionalization of 7‐azaindole by controlled annular directed Metalation group isomerism is reported. The N‐7 carbamoyl azaindoles 2a–b undergo regioselective Metalation and electrophile quench to furnish C‐6 substituted derivatives 3 which, in the presence of catalytic amount of ClCONR2 afford products 4 by an N‐7 to N‐1 carbamoyl group dance. A second directed Metalation‐electrophile quench sequence leads to 2,6‐substituted azaindoles 5. Optimization of Metalation conditions for C‐2 and C‐6, separately and iteratively, is presented. Using the directed Metalation group dance strategy, a late‐stage deuteration of an antipsychotic drug is described. Overall, the controlled annular isomerism of a carbamoyl directing group allows multiple functionalization events of the bioactive azaindole scaffold.
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directed ortho Metalation and anionic ortho fries rearrangement of polycyclic aromatic o carbamates regioselective synthesis of substituted chrysenes
Journal of Organic Chemistry, 2018Co-Authors: Sindhu Kancherla, Victor Snieckus, Marianne Lorentzen, Kare B JorgensenAbstract:A general method for the regioselective synthesis of a series of ortho-substituted chrysenyl N,N-diethyl-O-carbamates by the directed ortho-Metalation (DoM) strategy is reported. The starting O-carbamates were prepared from the corresponding chrysenols, available by oxidative photochemical cyclization or directed remote Metalation tactics. Chrysen-1-yl and chrysene-3-yl ring site selectivity of directed ortho-Metalation (DoM) and anionic ortho-Fries rearrangement (AoF) protocols, with s-BuLi/TMEDA, followed by electrophilic quench using a selection of electrophiles, were observed, leading to new chrysenyl derivatives. 5-Chrysenyl N,N-diethyl-O-carbamate underwent instant AoF rearrangement even at −100 °C to furnish chrysenyl o-hydroxycarboxamide. Iterative DoM reactions were carried out to gain insight into the regioselectivity factors.
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Directed ortho-Metalation and Anionic ortho-Fries Rearrangement of Polycyclic Aromatic O‑Carbamates: Regioselective Synthesis of Substituted Chrysenes
2018Co-Authors: Sindhu Kancherla, Victor Snieckus, Marianne Lorentzen, Kare B JorgensenAbstract:A general method for the regioselective synthesis of a series of ortho-substituted chrysenyl N,N-diethyl-O-carbamates by the directed ortho-Metalation (DoM) strategy is reported. The starting O-carbamates were prepared from the corresponding chrysenols, available by oxidative photochemical cyclization or directed remote Metalation tactics. Chrysen-1-yl and chrysene-3-yl ring site selectivity of directed ortho-Metalation (DoM) and anionic ortho-Fries rearrangement (AoF) protocols, with s-BuLi/TMEDA, followed by electrophilic quench using a selection of electrophiles, were observed, leading to new chrysenyl derivatives. 5-Chrysenyl N,N-diethyl-O-carbamate underwent instant AoF rearrangement even at −100 °C to furnish chrysenyl o-hydroxycarboxamide. Iterative DoM reactions were carried out to gain insight into the regioselectivity factors
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directed Metalation suzuki miyaura cross coupling strategies regioselective synthesis of hydroxylated 1 methyl phenanthrenes
Journal of Organic Chemistry, 2015Co-Authors: Kare B Jorgensen, Toni Rantanen, Thilo Dorfler, Victor SnieckusAbstract:A general, efficient, and regioselective synthesis of a series of hydroxylated 1-methylphenanthrenes 9 by a combined directed ortho Metalation (DoM)–Suzuki–Miyaura cross-coupling–directed remote Metalation (DreM) sequence is reported. Diversity to this methodology was achieved by a regioselective DoM rather than DreM reaction, affording more highly substituted phenanthrols (Table 2). Application of the turbo-Grignard reagent (i-PrMgCl·LiCl) in the Ni-catalyzed Corriu–Kumada reaction gave efficient decarbamoylation (Tables 3 and 4). Additional features are the TMS protecting group and halo-induced ipso-desilylation tactics applied to the regioselective synthesis of phenanthrenes (Scheme 2).
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directed ortho Metalation strategies effective regioselective routes to 1 2 2 3 and 1 2 3 substituted naphthalenes
ChemInform, 2014Co-Authors: Katherine Groom, S Shakil M Hussain, Justin Morin, Christian Nilewski, Toni Rantanen, Victor SnieckusAbstract:Directed ortho-Metalation of naphthyl-2-carbamate followed by reaction with various electrophiles affords di- and trisubstituted naphthalenes with high regioselectivity.
Paul Knochel - One of the best experts on this subject based on the ideXlab platform.
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preparation of functionalized aryl heteroaryl and benzylic potassium organometallics using potassium diisopropylamide in continuous flow
Angewandte Chemie, 2020Co-Authors: Johannes H Harenberg, Niels Weidmann, Paul KnochelAbstract:We report the preparation of lithium-salt-free KDA (potassium diisopropylamide; 0.6 m in hexane) complexed with TMEDA (N,N,N',N'-tetramethylethylenediamine) and its use for the flow-Metalation of (hetero)arenes between -78 °C and 25 °C with reaction times between 0.2 s and 24 s and a combined flow rate of 10 mL min-1 using a commercial flow setup. The resulting potassium organometallics react instantaneously with various electrophiles, such as ketones, aldehydes, alkyl and allylic halides, disulfides, Weinreb amides, and Me3 SiCl, affording functionalized (hetero)arenes in high yields. This flow procedure is successfully extended to the lateral Metalation of methyl-substituted arenes and heteroaromatics, resulting in the formation of various benzylic potassium organometallics. A Metalation scale-up was possible without further optimization.
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regioselective c h activation of substituted pyridines and other azines using mg and zn tmp bases
SynOpen, 2018Co-Authors: Moritz Balkenhohl, Paul KnochelAbstract:The Metalation of substituted pyridines, diazines and related N -heterocycles using TMPMgCl·LiCl, TMP 2 Mg·2LiCl, TMPZnCl·LiCl or TMP 2 Zn·2LiCl 2 ·2MgCl 2 (TMP = 2,2,6,6-tetramethylpiperidyl) in the presence or absence of a Lewis acid is reviewed. Contents 1 Introduction 2 Magnesiation of Pyridines and Related Azines 2.1 Magnesiations using TMPMgCl·LiCl 2.2 Magnesiations using TMP 2 Mg·2LiCl and Related Bases 2.3 BF 3 ·OEt 2 Promoted Metalations of Pyridines 3 Zincation of Pyridines and Related Azines using TMPZnCl·LiCl and TMP 2 Zn·2LiCl·2MgCl 2 4 Metalation of Pyridines using other TMP-Bases 5 Magnesiation and Zincation of Diazines 6 Conclusion
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selective lithiation magnesiation and zincation of unsymmetrical azobenzenes using continuous flow
Organic Letters, 2017Co-Authors: Marthe Ketels, Konstantin Karaghiosoff, David B Konrad, Dirk Trauner, Paul KnochelAbstract:A mild and general set of Metalation procedures for the functionalization of unsymmetrical azobenzenes using a commercially available continuous-flow setup is reported. The Metalations proceed with TMPLi under convenient conditions (0 °C, 20 s), and various classes of electrophiles can be used. With sensitive substrates, an in situ trapping Metalation in which TMPLi is added to a mixture of the azobenzene and ZnCl2 or MgCl2·LiCl was very effective for achieving high yields.
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lewis acid triggered regioselective magnesiation and zincation of uracils uridines and cytidines
Organic Letters, 2016Co-Authors: Lydia Klier, Eider Aranzamendi, Dorothee Ziegler, Konstantin Karaghiosoff, Thomas Carell, Johannes Nickel, Paul KnochelAbstract:The Lewis acid MgCl2 allows control of the Metalation regioselectivity of uracils and uridines. In the absence of the Lewis acid, Metalation of uracil and uridine derivatives with TMPMgCl·LiCl occurs at the position C(5). In the presence of MgCl2, zincation using TMP2Zn·2LiCl·2MgCl2 occurs at the position C(6). This Metalation method provides easy access to functionalized uracils and uridines. Using TMP2Zn·2LiCl·2MgCl2 also allows to functionalize cytidine derivatives at the position C(6).
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continuous flow magnesiation or zincation of acrylonitriles acrylates and nitroolefins application to the synthesis of butenolides
Organic Letters, 2016Co-Authors: Maximilian A Ganiek, Marthe Ketels, Matthias R Becker, Paul KnochelAbstract:Scalable continuous flow procedures are reported for the Metalation and downstream functionalization of β-substituted acrylates. The flow conditions allow the Metalation of acrylonitriles, acrylates, and nitroolefins at 0.25–2.50 mmol/min conversion rates. Magnesiations can be performed with short residence times (1–20 min) and near-ambient temperature using TMPMgCl·LiCl. Further, high temperature zincation (≤90 °C) using TMPZnCl·LiCl is possible. This method allows a simple entry to 2(5H)-furanones by flow generation of magnesiated acrylates and a subsequent reaction with aldehydes.
Kare B Jorgensen - One of the best experts on this subject based on the ideXlab platform.
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directed ortho Metalation and anionic ortho fries rearrangement of polycyclic aromatic o carbamates regioselective synthesis of substituted chrysenes
Journal of Organic Chemistry, 2018Co-Authors: Sindhu Kancherla, Victor Snieckus, Marianne Lorentzen, Kare B JorgensenAbstract:A general method for the regioselective synthesis of a series of ortho-substituted chrysenyl N,N-diethyl-O-carbamates by the directed ortho-Metalation (DoM) strategy is reported. The starting O-carbamates were prepared from the corresponding chrysenols, available by oxidative photochemical cyclization or directed remote Metalation tactics. Chrysen-1-yl and chrysene-3-yl ring site selectivity of directed ortho-Metalation (DoM) and anionic ortho-Fries rearrangement (AoF) protocols, with s-BuLi/TMEDA, followed by electrophilic quench using a selection of electrophiles, were observed, leading to new chrysenyl derivatives. 5-Chrysenyl N,N-diethyl-O-carbamate underwent instant AoF rearrangement even at −100 °C to furnish chrysenyl o-hydroxycarboxamide. Iterative DoM reactions were carried out to gain insight into the regioselectivity factors.
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Directed ortho-Metalation and Anionic ortho-Fries Rearrangement of Polycyclic Aromatic O‑Carbamates: Regioselective Synthesis of Substituted Chrysenes
2018Co-Authors: Sindhu Kancherla, Victor Snieckus, Marianne Lorentzen, Kare B JorgensenAbstract:A general method for the regioselective synthesis of a series of ortho-substituted chrysenyl N,N-diethyl-O-carbamates by the directed ortho-Metalation (DoM) strategy is reported. The starting O-carbamates were prepared from the corresponding chrysenols, available by oxidative photochemical cyclization or directed remote Metalation tactics. Chrysen-1-yl and chrysene-3-yl ring site selectivity of directed ortho-Metalation (DoM) and anionic ortho-Fries rearrangement (AoF) protocols, with s-BuLi/TMEDA, followed by electrophilic quench using a selection of electrophiles, were observed, leading to new chrysenyl derivatives. 5-Chrysenyl N,N-diethyl-O-carbamate underwent instant AoF rearrangement even at −100 °C to furnish chrysenyl o-hydroxycarboxamide. Iterative DoM reactions were carried out to gain insight into the regioselectivity factors
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directed Metalation suzuki miyaura cross coupling strategies regioselective synthesis of hydroxylated 1 methyl phenanthrenes
Journal of Organic Chemistry, 2015Co-Authors: Kare B Jorgensen, Toni Rantanen, Thilo Dorfler, Victor SnieckusAbstract:A general, efficient, and regioselective synthesis of a series of hydroxylated 1-methylphenanthrenes 9 by a combined directed ortho Metalation (DoM)–Suzuki–Miyaura cross-coupling–directed remote Metalation (DreM) sequence is reported. Diversity to this methodology was achieved by a regioselective DoM rather than DreM reaction, affording more highly substituted phenanthrols (Table 2). Application of the turbo-Grignard reagent (i-PrMgCl·LiCl) in the Ni-catalyzed Corriu–Kumada reaction gave efficient decarbamoylation (Tables 3 and 4). Additional features are the TMS protecting group and halo-induced ipso-desilylation tactics applied to the regioselective synthesis of phenanthrenes (Scheme 2).
Toni Rantanen - One of the best experts on this subject based on the ideXlab platform.
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directed Metalation suzuki miyaura cross coupling strategies regioselective synthesis of hydroxylated 1 methyl phenanthrenes
Journal of Organic Chemistry, 2015Co-Authors: Kare B Jorgensen, Toni Rantanen, Thilo Dorfler, Victor SnieckusAbstract:A general, efficient, and regioselective synthesis of a series of hydroxylated 1-methylphenanthrenes 9 by a combined directed ortho Metalation (DoM)–Suzuki–Miyaura cross-coupling–directed remote Metalation (DreM) sequence is reported. Diversity to this methodology was achieved by a regioselective DoM rather than DreM reaction, affording more highly substituted phenanthrols (Table 2). Application of the turbo-Grignard reagent (i-PrMgCl·LiCl) in the Ni-catalyzed Corriu–Kumada reaction gave efficient decarbamoylation (Tables 3 and 4). Additional features are the TMS protecting group and halo-induced ipso-desilylation tactics applied to the regioselective synthesis of phenanthrenes (Scheme 2).
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directed ortho Metalation strategies effective regioselective routes to 1 2 2 3 and 1 2 3 substituted naphthalenes
ChemInform, 2014Co-Authors: Katherine Groom, S Shakil M Hussain, Justin Morin, Christian Nilewski, Toni Rantanen, Victor SnieckusAbstract:Directed ortho-Metalation of naphthyl-2-carbamate followed by reaction with various electrophiles affords di- and trisubstituted naphthalenes with high regioselectivity.
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directed ortho Metalation strategies effective regioselective routes to 1 2 2 3 and 1 2 3 substituted naphthalenes
Organic Letters, 2014Co-Authors: Katherine Groom, S Shakil M Hussain, Justin Morin, Christian Nilewski, Toni Rantanen, Victor SnieckusAbstract:The regioselective synthesis of 2,3-di- and 1,2,3-trisubstituted naphthalenes via Directed ortho Metalation (DoM) strategies of N,N-diethyl-O-naphthyl-2-carbamate (1) is presented. Sequential LiTMP Metalation–electrophile quench and s-BuLi/TMEDA (or t-BuLi)-electrophile quench of naphthyl-2-carbamate 1 provides a general route to contiguously substituted naphthalenes (6) with full regioselectivity. Further derivatization via ipso-halodesilylation and Suzuki–Miyaura cross-coupling leads ultimately to substituted halonaphthalenes and benzonaphthopyranones (9).
Katherine Groom - One of the best experts on this subject based on the ideXlab platform.
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directed ortho Metalation strategies effective regioselective routes to 1 2 2 3 and 1 2 3 substituted naphthalenes
ChemInform, 2014Co-Authors: Katherine Groom, S Shakil M Hussain, Justin Morin, Christian Nilewski, Toni Rantanen, Victor SnieckusAbstract:Directed ortho-Metalation of naphthyl-2-carbamate followed by reaction with various electrophiles affords di- and trisubstituted naphthalenes with high regioselectivity.
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directed ortho Metalation strategies effective regioselective routes to 1 2 2 3 and 1 2 3 substituted naphthalenes
Organic Letters, 2014Co-Authors: Katherine Groom, S Shakil M Hussain, Justin Morin, Christian Nilewski, Toni Rantanen, Victor SnieckusAbstract:The regioselective synthesis of 2,3-di- and 1,2,3-trisubstituted naphthalenes via Directed ortho Metalation (DoM) strategies of N,N-diethyl-O-naphthyl-2-carbamate (1) is presented. Sequential LiTMP Metalation–electrophile quench and s-BuLi/TMEDA (or t-BuLi)-electrophile quench of naphthyl-2-carbamate 1 provides a general route to contiguously substituted naphthalenes (6) with full regioselectivity. Further derivatization via ipso-halodesilylation and Suzuki–Miyaura cross-coupling leads ultimately to substituted halonaphthalenes and benzonaphthopyranones (9).