CHEMSUSCHEM HIGHLIGHTS DOI: 10.1002/cssc.201402320
Advances in Asymmetric Borrowing Hydrogen Catalysis Dirk Hollmann*[a]
Tremendous efforts have been directed towards the conversion of stoichiometric reactions into catalytic processes leading to a minimized E factor.[1] In this regard, asymmetric catalysis has enabled the selective synthesis of chiral products to circumvent the separation of racemic mixtures. Therefore, it has become one of the most important topics in organic chemistry. To avoid multi-step reactions and expensive separation processes, new concepts have been developed. Over the years, immense expenditure to utilize sequential one-pot procedures without purification has been conducted. A powerful strategy is the borrowing hydrogen (BH) methodology, which combines transfer hydrogenation (avoidance of direct usage of hydrogen) with an intermediate reaction, such as condensation or aalkylation, without necessary separation processes.[2] Utilizing this highly efficient technique, carbon–carbon or carbon–nitrogen bonds[3] can be formed (Scheme 1).
Scheme 1. The hydrogen borrowing principle: This one-step transformation (red arrow) is achieved by a catalyst that enables all intermediate steps through selective hydrogen uptake or release. Bond formation could occur at a-(X), b-(R3), and g-(R4) position. R1–R4 = general substituents.
In the initial step, a racemic alcohol is activated through dehydrogenation, resulting in the formation of a transient ketone species that can undergo further transformations. The second unsaturated intermediate can then be hydrogenated by the metal-hydride complex obtained during dehydrogenation. However, so far only racemic alcohols or amines have been synthesized, which limits this application to bulk chemicals. In [a] Dr. D. Hollmann Leibniz-Institut fr Katalyse e.V. an der Universitt Rostock Albert-Einstein-Str. 29 A, 18059 Rostock (Germany) Fax: (+ 49) 381-1281-352 E-mail: [email protected]
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
recent years, two major challenges have been addressed that promote asymmetric BH methods; those challenges are 1) decreasing reaction temperatures below 40 8C and 2) improving compatibility of the chiral organocatalyst and the metal catalyst. Transition-metal BH catalysts based on iridium, rhodium, ruthenium as well as iron[4] tend to generate amine–metal complexes with the organocatalyst, which results in overall catalyst inhibition. As a result, this research field stagnated to a certain extent. Note that with the exception of a report in 2007 by Williams and co-workers,[5] no asymmetric approaches with high enantiomeric excess (ee) have been reported.[6] Applying a chiral iridium catalyst generated from [Ir(cod)Cl]2/RBINAP (COD = 1,5-cyclooctadiene; BINAP = 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl), an asymmetric BH-Wittig reaction with ee values up to 83 % was demonstrated for one substrate. Despite this promising result, this catalyst system was not employed for further asymmetric BH applications (e.g., amination of alcohols or amines). Recently, Quintard et al.[7] and Zhao et al.[8] reported two important breakthroughs in BH processes that expanded this field to asymmetric catalysis. Quintard and co-workers[7] reported the first combination of the BH principle with organocatalysis.[9] Therein, one stereocenter was introduced at the a-position (with respect to the alcohol substrate) through activation of an iminium ion generated from the transient a,b-unsaturated aldehyde (Scheme 2 a) followed by enantioselective Michael addition. Notably, mild conditions (10 8C to RT) could be applied to this reaction cascade. The Shvo-like iron-based Knçlker complex[10] was employed as a hydrogen transfer catalyst in this case, which allows hydrogenation as well as dehydrogenation in the presence of amine organocatalysts without inhibition. These results represent the first examples of catalyst compatibility combined with a low temperature protocol. However, the Knçlker catalyst is air sensitive and decomposes quickly, thus requiring in situ generation from the tricarbonyl iron precursor 1 and trimethylamine N-oxide. Further catalyst improvement focused on increased selectivity, yields (> 95 %), enantiomeric ratio as well as on an expanded substrate scope in combination with higher functional-group tolerance. The scope of substrates was limited to strong nucleophiles (keto ester) and simple allyl alcohols (crotyl/cinnamyl alcohols).[7] Zhao and co-workers[8] reported the enantioselective amination of alcohols. One stereocenter at the a-position was introduced during the final hydrogenation step via an intermediate chiral iminium-phosphate pair[11] (Scheme 2 b). Secondary aryl amines were obtained in high yields and ee values up to 97 %. Although lowering the reaction temperature improved the ee value, the conversion was decreased. This protocol was successfully applied to arylamines. Alkylamines and amides were ChemSusChem 0000, 00, 1 – 4
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These are not the final page numbers! ÞÞ
CHEMSUSCHEM HIGHLIGHTS
www.chemsuschem.org
Scheme 2. New asymmetric borrowing hydrogen concepts. Nu = nucleophile; L-Fe/Ir = corresponding hydrogen transfer catalyst; Cp* = pentamethylcyclopentadienyl; TMS = trimethylsilyl; R1–R4 = general substituents.
also tested, but low yields or ee values were obtained. Different functional groups such as ether or halides were tolerated, but no examples with more challenging functional groups (nitro or amides) were described. Notably, intramolecular amination proceeded smoothly. Remarkably, the reactions were performed at high temperatures (> 100 8C) with the chiral iridium catalyst 3 and the chiral phosphoric acid 4. The phosphoric acid 4 acts as Brønsted acid to form a chiral iminium–phosphate pair as well as an activation reagent for the chiral iridium complex through protonation. Furthermore, 4 is essential for the stereoselective reduction. Here, the transition state involves the iminium, the chiral phosphate as well as the chiral iridium hydrogen-transfer catalyst connected through hydrogen bonds.[12] This could explain the intermolecular match/mismatch relationship (also known as kinetic discrimination[13]) of both catalysts. Thus, only an appropriate catalyst mixture of chiral Brønsted acid and metal complex provides high activity and selectivity. Both publications could be perceived as milestones for the further application of the BH methodology. Prior to these reports, the production of chiral amines/alcohols (via BH) constitutes a major challenge in BH. Now, using both methods, an iron-catalyzed low temperature process as well as through a high-temperature-stable chiral iminium–phosphate pair, racemic mixtures can easily be converted enantioselectively to the corresponding alcohols and amines. Thus, the enantioselective amination of alcohols could be considered as an alternative to oxidation of alcohols followed by enantioselective reductive amination. Nevertheless, since only a limited scope of catalysts exists for the asymmetric BH, it is highly desired to develop new or 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ganic as well as inorganic catalysts to utilize the asymmetric BH methodology for further applications. Theoretically, these general approaches are not restricted to the reported systems and thus could be applied to a wide range of other enantioselective applications in BH, for example, chiral primary amines (via racemic alcohols and ammonia),[14] enantiopure amines (through amination of racemic amines),[15] or selective deracemization of alcohols or diols. Furthermore, application of organocatalysis,[9] for example, selective asymmetric functionalization of the b-position via enamines,[16] could expand the BH principle. Thus, rethinking of these concepts could push the applications even towards asymmetric natural product synthesis.
Acknowledgements Financial support from the Federal Ministry of Education and Research of Germany (BMBF) within the project “Light2Hydrogen” is gratefully acknowledged. Keywords: asymmetric catalysis · borrowing hydrogen · enantioselectivity · organocatalysis · synthetic methods [1] R. A. Sheldon, Chem. Commun. 2008, 3352 – 3365. [2] a) S. Bhn, S. Imm, L. Neubert, M. Zhang, H. Neumann, M. Beller, ChemCatChem 2011, 3, 1853 – 1864; b) A. J. A. Watson, J. M. J. Williams, Science 2010, 329, 635 – 636; c) G. Guillena, D. J. Ramn, M. Yus, Chem. Rev. 2010, 110, 1611 – 1641. [3] J. Schranck, A. Tlili, M. Beller, Angew. Chem. Int. Ed. 2013, 52, 7642 – 7644; Angew. Chem. 2013, 125, 7795 – 7797. [4] Y. Zhao, S. W. Foo, S. Saito, Angew. Chem. Int. Ed. 2011, 50, 3006 – 3009; Angew. Chem. 2011, 123, 3062 – 3065.
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CHEMSUSCHEM HIGHLIGHTS [5] D. J. Shermer, P. A. Slatford, D. D. Edney, J. M. J. Williams, Tetrahedron: Asymmetry 2007, 18, 2845 – 2848. [6] Moderate enantiomeric excess (< 70 %) was reported by Oe and coworkers: A. Eka Putra, Y. Oe, T. Ohta, Eur. J. Org. Chem. 2013, 6146 – 6151. [7] A. Quintard, T. Constantieux, J. Rodriguez, Angew. Chem. Int. Ed. 2013, 52, 12883 – 12887; Angew. Chem. 2013, 125, 13121 – 13125. [8] Y. Zhang, C.-S. Lim, D. S. B. Sim, H.-J. Pan, Y. Zhao, Angew. Chem. Int. Ed. 2014, 53, 1399 – 1403; Angew. Chem. 2014, 126, 1423 – 1427. [9] S. Bertelsen, K. A. Jørgensen, Chem. Soc. Rev. 2009, 38, 2178 – 2189. [10] A. Pagnoux-Ozherelyeva, N. Pannetier, M. D. Mbaye, S. Gaillard, J.-L. Renaud, Angew. Chem. Int. Ed. 2012, 51, 4976 – 4980; Angew. Chem. 2012, 124, 5060 – 5064 and references therein. [11] R. J. Phipps, G. L. Hamilton, F. D. Toste, Nat. Chem. 2012, 4, 603 – 614. [12] W. Tang, S. Johnston, J. A. Iggo, N. G. Berry, M. Phelan, L. Lian, J. Bacsa, J. Xiao, Angew. Chem. Int. Ed. 2013, 52, 1668 – 1672; Angew. Chem. 2013, 125, 1712 – 1716.
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemsuschem.org [13] M. Rueping, R. M. Koenigs, I. Atodiresei, Chem. Eur. J. 2010, 16, 9350 – 9365. [14] a) C. Gunanathan, D. Milstein, Angew. Chem. Int. Ed. 2008, 47, 8661 – 8664; Angew. Chem. 2008, 120, 8789 – 8792; b) D. Pingen, C. Mller, D. Vogt, Angew. Chem. Int. Ed. 2010, 49, 8130 – 8133; Angew. Chem. 2010, 122, 8307 – 8310. [15] a) O. Saidi, A. J. Blacker, M. M. Farah, S. P. Marsden, J. M. J. Williams, Angew. Chem. Int. Ed. 2009, 48, 7375 – 7378; Angew. Chem. 2009, 121, 7511 – 7514; b) D. Hollmann, S. Baehn, A. Tillack, M. Beller, Angew. Chem. Int. Ed. 2007, 46, 8291 – 8294; Angew. Chem. 2007, 119, 8440 – 8444. [16] S. Mukherjee, J. W. Yang, S. Hoffmann, B. List, Chem. Rev. 2007, 107, 5471 – 5569.
Received: April 16, 2014 Published online on && &&, 0000
ChemSusChem 0000, 00, 1 – 4
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These are not the final page numbers! ÞÞ
HIGHLIGHTS D. Hollmann* && – && Advances in Asymmetric Borrowing Hydrogen Catalysis
Borrowing extends opportunities: Borrowing hydrogen (BH) catalysis represents a powerful and environmental alternative to known C C, C N, and C O formation schemes. Recently, two important approaches have been pub-
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
lished that extended this methodology to asymmetric catalysis. A short discussion combined with a perspective for the asymmetric BH is presented in this highlight.
ChemSusChem 0000, 00, 1 – 4
&4&
These are not the final page numbers! ÞÞ
Advances in Asymmetric Borrowing Hydrogen Catalysis Dirk Hollmann*[a]
Tremendous efforts have been directed towards the conversion of stoichiometric reactions into catalytic processes leading to a minimized E factor.[1] In this regard, asymmetric catalysis has enabled the selective synthesis of chiral products to circumvent the separation of racemic mixtures. Therefore, it has become one of the most important topics in organic chemistry. To avoid multi-step reactions and expensive separation processes, new concepts have been developed. Over the years, immense expenditure to utilize sequential one-pot procedures without purification has been conducted. A powerful strategy is the borrowing hydrogen (BH) methodology, which combines transfer hydrogenation (avoidance of direct usage of hydrogen) with an intermediate reaction, such as condensation or aalkylation, without necessary separation processes.[2] Utilizing this highly efficient technique, carbon–carbon or carbon–nitrogen bonds[3] can be formed (Scheme 1).
Scheme 1. The hydrogen borrowing principle: This one-step transformation (red arrow) is achieved by a catalyst that enables all intermediate steps through selective hydrogen uptake or release. Bond formation could occur at a-(X), b-(R3), and g-(R4) position. R1–R4 = general substituents.
In the initial step, a racemic alcohol is activated through dehydrogenation, resulting in the formation of a transient ketone species that can undergo further transformations. The second unsaturated intermediate can then be hydrogenated by the metal-hydride complex obtained during dehydrogenation. However, so far only racemic alcohols or amines have been synthesized, which limits this application to bulk chemicals. In [a] Dr. D. Hollmann Leibniz-Institut fr Katalyse e.V. an der Universitt Rostock Albert-Einstein-Str. 29 A, 18059 Rostock (Germany) Fax: (+ 49) 381-1281-352 E-mail: [email protected]
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
recent years, two major challenges have been addressed that promote asymmetric BH methods; those challenges are 1) decreasing reaction temperatures below 40 8C and 2) improving compatibility of the chiral organocatalyst and the metal catalyst. Transition-metal BH catalysts based on iridium, rhodium, ruthenium as well as iron[4] tend to generate amine–metal complexes with the organocatalyst, which results in overall catalyst inhibition. As a result, this research field stagnated to a certain extent. Note that with the exception of a report in 2007 by Williams and co-workers,[5] no asymmetric approaches with high enantiomeric excess (ee) have been reported.[6] Applying a chiral iridium catalyst generated from [Ir(cod)Cl]2/RBINAP (COD = 1,5-cyclooctadiene; BINAP = 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl), an asymmetric BH-Wittig reaction with ee values up to 83 % was demonstrated for one substrate. Despite this promising result, this catalyst system was not employed for further asymmetric BH applications (e.g., amination of alcohols or amines). Recently, Quintard et al.[7] and Zhao et al.[8] reported two important breakthroughs in BH processes that expanded this field to asymmetric catalysis. Quintard and co-workers[7] reported the first combination of the BH principle with organocatalysis.[9] Therein, one stereocenter was introduced at the a-position (with respect to the alcohol substrate) through activation of an iminium ion generated from the transient a,b-unsaturated aldehyde (Scheme 2 a) followed by enantioselective Michael addition. Notably, mild conditions (10 8C to RT) could be applied to this reaction cascade. The Shvo-like iron-based Knçlker complex[10] was employed as a hydrogen transfer catalyst in this case, which allows hydrogenation as well as dehydrogenation in the presence of amine organocatalysts without inhibition. These results represent the first examples of catalyst compatibility combined with a low temperature protocol. However, the Knçlker catalyst is air sensitive and decomposes quickly, thus requiring in situ generation from the tricarbonyl iron precursor 1 and trimethylamine N-oxide. Further catalyst improvement focused on increased selectivity, yields (> 95 %), enantiomeric ratio as well as on an expanded substrate scope in combination with higher functional-group tolerance. The scope of substrates was limited to strong nucleophiles (keto ester) and simple allyl alcohols (crotyl/cinnamyl alcohols).[7] Zhao and co-workers[8] reported the enantioselective amination of alcohols. One stereocenter at the a-position was introduced during the final hydrogenation step via an intermediate chiral iminium-phosphate pair[11] (Scheme 2 b). Secondary aryl amines were obtained in high yields and ee values up to 97 %. Although lowering the reaction temperature improved the ee value, the conversion was decreased. This protocol was successfully applied to arylamines. Alkylamines and amides were ChemSusChem 0000, 00, 1 – 4
&1&
These are not the final page numbers! ÞÞ
CHEMSUSCHEM HIGHLIGHTS
www.chemsuschem.org
Scheme 2. New asymmetric borrowing hydrogen concepts. Nu = nucleophile; L-Fe/Ir = corresponding hydrogen transfer catalyst; Cp* = pentamethylcyclopentadienyl; TMS = trimethylsilyl; R1–R4 = general substituents.
also tested, but low yields or ee values were obtained. Different functional groups such as ether or halides were tolerated, but no examples with more challenging functional groups (nitro or amides) were described. Notably, intramolecular amination proceeded smoothly. Remarkably, the reactions were performed at high temperatures (> 100 8C) with the chiral iridium catalyst 3 and the chiral phosphoric acid 4. The phosphoric acid 4 acts as Brønsted acid to form a chiral iminium–phosphate pair as well as an activation reagent for the chiral iridium complex through protonation. Furthermore, 4 is essential for the stereoselective reduction. Here, the transition state involves the iminium, the chiral phosphate as well as the chiral iridium hydrogen-transfer catalyst connected through hydrogen bonds.[12] This could explain the intermolecular match/mismatch relationship (also known as kinetic discrimination[13]) of both catalysts. Thus, only an appropriate catalyst mixture of chiral Brønsted acid and metal complex provides high activity and selectivity. Both publications could be perceived as milestones for the further application of the BH methodology. Prior to these reports, the production of chiral amines/alcohols (via BH) constitutes a major challenge in BH. Now, using both methods, an iron-catalyzed low temperature process as well as through a high-temperature-stable chiral iminium–phosphate pair, racemic mixtures can easily be converted enantioselectively to the corresponding alcohols and amines. Thus, the enantioselective amination of alcohols could be considered as an alternative to oxidation of alcohols followed by enantioselective reductive amination. Nevertheless, since only a limited scope of catalysts exists for the asymmetric BH, it is highly desired to develop new or 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ganic as well as inorganic catalysts to utilize the asymmetric BH methodology for further applications. Theoretically, these general approaches are not restricted to the reported systems and thus could be applied to a wide range of other enantioselective applications in BH, for example, chiral primary amines (via racemic alcohols and ammonia),[14] enantiopure amines (through amination of racemic amines),[15] or selective deracemization of alcohols or diols. Furthermore, application of organocatalysis,[9] for example, selective asymmetric functionalization of the b-position via enamines,[16] could expand the BH principle. Thus, rethinking of these concepts could push the applications even towards asymmetric natural product synthesis.
Acknowledgements Financial support from the Federal Ministry of Education and Research of Germany (BMBF) within the project “Light2Hydrogen” is gratefully acknowledged. Keywords: asymmetric catalysis · borrowing hydrogen · enantioselectivity · organocatalysis · synthetic methods [1] R. A. Sheldon, Chem. Commun. 2008, 3352 – 3365. [2] a) S. Bhn, S. Imm, L. Neubert, M. Zhang, H. Neumann, M. Beller, ChemCatChem 2011, 3, 1853 – 1864; b) A. J. A. Watson, J. M. J. Williams, Science 2010, 329, 635 – 636; c) G. Guillena, D. J. Ramn, M. Yus, Chem. Rev. 2010, 110, 1611 – 1641. [3] J. Schranck, A. Tlili, M. Beller, Angew. Chem. Int. Ed. 2013, 52, 7642 – 7644; Angew. Chem. 2013, 125, 7795 – 7797. [4] Y. Zhao, S. W. Foo, S. Saito, Angew. Chem. Int. Ed. 2011, 50, 3006 – 3009; Angew. Chem. 2011, 123, 3062 – 3065.
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These are not the final page numbers! ÞÞ
CHEMSUSCHEM HIGHLIGHTS [5] D. J. Shermer, P. A. Slatford, D. D. Edney, J. M. J. Williams, Tetrahedron: Asymmetry 2007, 18, 2845 – 2848. [6] Moderate enantiomeric excess (< 70 %) was reported by Oe and coworkers: A. Eka Putra, Y. Oe, T. Ohta, Eur. J. Org. Chem. 2013, 6146 – 6151. [7] A. Quintard, T. Constantieux, J. Rodriguez, Angew. Chem. Int. Ed. 2013, 52, 12883 – 12887; Angew. Chem. 2013, 125, 13121 – 13125. [8] Y. Zhang, C.-S. Lim, D. S. B. Sim, H.-J. Pan, Y. Zhao, Angew. Chem. Int. Ed. 2014, 53, 1399 – 1403; Angew. Chem. 2014, 126, 1423 – 1427. [9] S. Bertelsen, K. A. Jørgensen, Chem. Soc. Rev. 2009, 38, 2178 – 2189. [10] A. Pagnoux-Ozherelyeva, N. Pannetier, M. D. Mbaye, S. Gaillard, J.-L. Renaud, Angew. Chem. Int. Ed. 2012, 51, 4976 – 4980; Angew. Chem. 2012, 124, 5060 – 5064 and references therein. [11] R. J. Phipps, G. L. Hamilton, F. D. Toste, Nat. Chem. 2012, 4, 603 – 614. [12] W. Tang, S. Johnston, J. A. Iggo, N. G. Berry, M. Phelan, L. Lian, J. Bacsa, J. Xiao, Angew. Chem. Int. Ed. 2013, 52, 1668 – 1672; Angew. Chem. 2013, 125, 1712 – 1716.
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemsuschem.org [13] M. Rueping, R. M. Koenigs, I. Atodiresei, Chem. Eur. J. 2010, 16, 9350 – 9365. [14] a) C. Gunanathan, D. Milstein, Angew. Chem. Int. Ed. 2008, 47, 8661 – 8664; Angew. Chem. 2008, 120, 8789 – 8792; b) D. Pingen, C. Mller, D. Vogt, Angew. Chem. Int. Ed. 2010, 49, 8130 – 8133; Angew. Chem. 2010, 122, 8307 – 8310. [15] a) O. Saidi, A. J. Blacker, M. M. Farah, S. P. Marsden, J. M. J. Williams, Angew. Chem. Int. Ed. 2009, 48, 7375 – 7378; Angew. Chem. 2009, 121, 7511 – 7514; b) D. Hollmann, S. Baehn, A. Tillack, M. Beller, Angew. Chem. Int. Ed. 2007, 46, 8291 – 8294; Angew. Chem. 2007, 119, 8440 – 8444. [16] S. Mukherjee, J. W. Yang, S. Hoffmann, B. List, Chem. Rev. 2007, 107, 5471 – 5569.
Received: April 16, 2014 Published online on && &&, 0000
ChemSusChem 0000, 00, 1 – 4
&3&
These are not the final page numbers! ÞÞ
HIGHLIGHTS D. Hollmann* && – && Advances in Asymmetric Borrowing Hydrogen Catalysis
Borrowing extends opportunities: Borrowing hydrogen (BH) catalysis represents a powerful and environmental alternative to known C C, C N, and C O formation schemes. Recently, two important approaches have been pub-
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
lished that extended this methodology to asymmetric catalysis. A short discussion combined with a perspective for the asymmetric BH is presented in this highlight.
ChemSusChem 0000, 00, 1 – 4
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These are not the final page numbers! ÞÞ
