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Synergistic Gold and Iron Dual Catalysis: Preferred Radical Addition toward Vinyl-Gold Intermediate over Alkene Haihui Peng, Novruz G Akhmedov, Yu-Feng Liang, Ning Jiao, and Xiaodong Shi J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b05415 • Publication Date (Web): 02 Jul 2015 Downloaded from http://pubs.acs.org on July 6, 2015
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
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Journal of the American Chemical Society
Synergistic Gold and Iron Dual Catalysis: Preferred Radical Addition toward Vinyl-‐Gold Intermediate over Alkene Haihui Peng,a Novruz G. Akhmedov,a Yu-Feng Liang,b Ning Jiao,b,* and Xiaodong Shia,* a
C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506, USA State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road 38, Beijing 100191, China b
Supporting Information Placeholder ABSTRACT: A dual catalytic approach enlisting gold and iron synergy is described. This method offers a readily access to substituted heterocycle aldehydes via oxygen radical addition to vinyl-gold intermediates under Fe catalyst assistance. This system shows good functional group compatibility for the generation of substituted oxazole, indole and benzofuran aldehydes. Mechanistic evidence greatly supports selective radical addition to an activated vinyl-Au double bond over alkene. This unique discovery offers a new avenue with great potential to further extend the synthetic power and versatility of gold catalysis.
During the last decade, gold complexes have been proven to be one of the most effective catalysts for alkyne activation. In many cases, vinyl-gold complexes are recognized as key intermediates through inter- or intra-molecular nucleophilic addition toward alkyne-gold π-complexes.1 Thus, understanding vinyl-gold complex reactivity is crucial for new reaction discovery.2 One of the general reaction pathways of vinyl-gold intermediates is the protodeauration, converting a C-Au bond into C-H bond. 3 To further expand the scope, efforts have been made by various research groups in searching for new reactivity of vinyl-Au complexes. One exciting recent breakthrough was the discovery of Au(I)/Au(III) redox cycle originated from vinyl gold intermediates. Based on this new reaction mode, several new transformations have been achieved through gold catalyzed alkyne activation followed by vinyl-gold oxidative coupling (under either external oxidants or photocatalytic conditions, Scheme 1).4 It is clear that uncovering new reactivity of vinyl-gold complexes will benefit new transformation discovery. Herein, we report the synergistic Au/Fe catalysis as a new strategy to transform vinyl-gold intermediates by iron-oxygen radical addition.5 L III L Au R R. E.
Strong oxidant Oxidation
or Photocatalyst
R ref 4 Nu
Nu
[Au] -H+ NuH
H Protodeauration
Nu vinyl-gold
This work: Au-radical synergistic catalysis
Nu could not be achieved [Au] through reaction relay
[Fe] cat. O2
O Nu
O
[Fe]
X [Fe]/O2
-H2O
O Nu
Scheme 1. Vinyl-gold as crucial intermediates in gold catalysis
Regarding the combination of gold catalysis and radical chemistry, there are two typical reaction scenarios: A) reaction relay (sequential alkyne activation and radical addition to alkene) and B) synergistic catalysis (selective radical addition to vinyl gold over alkene). In theory, synergistic catalysis would facilitate new transformations that could not be achieved through simple stepwise reaction relay. This is particularly important for reactions involving slow protodeauration step. The key concerns were compatibility and orthogonal reactivity of the two catalytic systems. To explore the possibility of this new gold/radical synergistic catalysis, we selected the gold catalyzed propargyl amide cyclization as the model reaction.6 As shown in Figure 1, gold catalyst promotes the 5-exo-dig cyclization of alkyne amide 1a under mild conditions. The alkene product 2a can be isolated. Hashmi and coworkers reported the oxidation of 2a by molecular oxygen over time to give oxazole peroxide 3a.7 [Au] cat.
Radical conditions
N3
10% AgNO3
no desired products
X
O
TMSN3, 71% new
N 3b
Ph
not compatible
O Ph HN 1a
5% PPh3AuNTf2 r.t., CH3CN
OOH O Ph
N 3a
known THF, O2, 50 oC 48 h, 82%
Hashmi et al, ref 7
10% FeCl2
O Ph
2a
N
Togni reagent 55% new
CF3
O N 3c
Ph
SO2Ph 10% CuI PhSO2H, 83% Ph new
O N 3d
Figure 1. Gold catalysis and radical reaction-relay To test the reaction compatibility with gold catalyst, we explored reactions of alkene 2a with various radical species. As shown in Figure 1, new and mild radical conditions were developed for access to synthetically attractive oxazole derivatives, including azide (3b), CF3 (3c) and sulfone (3d).8 Notably, oxazole derivatives are very important building blocks in medicinal and biological research and these new strategies offered practical and efficient ways to synthesize this class of compounds.9 However, direct treatment of 1a with the combination of gold catalyst and these newly developed radical conditions gave complex reaction mixtures with no desired product observed. Clearly, the compatibility between gold catalyst and radical conditions is one crucial challenge for the development of the proposed synergistic catalysis. The recent successes in photocatalyst promoted gold redox chemistry suggested good compatibility between gold complexes and photocatalysts.10 Inspired by those results, we tested the reac-
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Journal of the American Chemical Society
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tivity of 1a with the combination of gold and photo catalysts under 1 atm O2. Interestingly, as shown in Figure 2A, besides the ring opening product 4a and aromatization product 4b, the oxazole-aldehyde 5a was obtained, albeit in low yield. These results suggested good compatibility of oxygen radical with gold catalyst. To improve the reaction performance, we directed our attention towards searching for other oxygen radical initiation conditions.11 As shown in Figure 2B, Fe(acac)3 was identified as the optimal catalyst (see detailed screening conditions in SI), which promoted the oxidation of 1a to oxazole-aldehyde 5a (80% conversion and 61% yield) simply with 1 atm molecular oxygen at room temperature. In addition, 18O labeled experiment confirmed that the aldehyde oxygen was originated from O2. Finally, addition of 50% tBuOOH helped the reaction to reach completion, giving 5a in 83% isolated yield, which highlighted the great compatibility of the Fe/O2 radical conditions with gold catalysis (Figure 2C). (A)
O
O
PPh3AuNTf2 (5 mol%)
Ph
[Ir] or [Ru] (2.5 mol%) Ph hv, r.t.
HN 1a
O
N H
4b
4a
conversion
4a
4b
Ir(ppy)3
100%
0%
20%
[Ir(ppy)2(bpy)]+PF6-
100%
75%
trace
0%
[Ru(bpy)3]2+
100%
33%
15%
Communication
Synergistic Gold and Iron Dual Catalysis: Preferred Radical Addition toward Vinyl-Gold Intermediate over Alkene Haihui Peng, Novruz G Akhmedov, Yu-Feng Liang, Ning Jiao, and Xiaodong Shi J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b05415 • Publication Date (Web): 02 Jul 2015 Downloaded from http://pubs.acs.org on July 6, 2015
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 6
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Journal of the American Chemical Society
Synergistic Gold and Iron Dual Catalysis: Preferred Radical Addition toward Vinyl-‐Gold Intermediate over Alkene Haihui Peng,a Novruz G. Akhmedov,a Yu-Feng Liang,b Ning Jiao,b,* and Xiaodong Shia,* a
C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506, USA State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road 38, Beijing 100191, China b
Supporting Information Placeholder ABSTRACT: A dual catalytic approach enlisting gold and iron synergy is described. This method offers a readily access to substituted heterocycle aldehydes via oxygen radical addition to vinyl-gold intermediates under Fe catalyst assistance. This system shows good functional group compatibility for the generation of substituted oxazole, indole and benzofuran aldehydes. Mechanistic evidence greatly supports selective radical addition to an activated vinyl-Au double bond over alkene. This unique discovery offers a new avenue with great potential to further extend the synthetic power and versatility of gold catalysis.
During the last decade, gold complexes have been proven to be one of the most effective catalysts for alkyne activation. In many cases, vinyl-gold complexes are recognized as key intermediates through inter- or intra-molecular nucleophilic addition toward alkyne-gold π-complexes.1 Thus, understanding vinyl-gold complex reactivity is crucial for new reaction discovery.2 One of the general reaction pathways of vinyl-gold intermediates is the protodeauration, converting a C-Au bond into C-H bond. 3 To further expand the scope, efforts have been made by various research groups in searching for new reactivity of vinyl-Au complexes. One exciting recent breakthrough was the discovery of Au(I)/Au(III) redox cycle originated from vinyl gold intermediates. Based on this new reaction mode, several new transformations have been achieved through gold catalyzed alkyne activation followed by vinyl-gold oxidative coupling (under either external oxidants or photocatalytic conditions, Scheme 1).4 It is clear that uncovering new reactivity of vinyl-gold complexes will benefit new transformation discovery. Herein, we report the synergistic Au/Fe catalysis as a new strategy to transform vinyl-gold intermediates by iron-oxygen radical addition.5 L III L Au R R. E.
Strong oxidant Oxidation
or Photocatalyst
R ref 4 Nu
Nu
[Au] -H+ NuH
H Protodeauration
Nu vinyl-gold
This work: Au-radical synergistic catalysis
Nu could not be achieved [Au] through reaction relay
[Fe] cat. O2
O Nu
O
[Fe]
X [Fe]/O2
-H2O
O Nu
Scheme 1. Vinyl-gold as crucial intermediates in gold catalysis
Regarding the combination of gold catalysis and radical chemistry, there are two typical reaction scenarios: A) reaction relay (sequential alkyne activation and radical addition to alkene) and B) synergistic catalysis (selective radical addition to vinyl gold over alkene). In theory, synergistic catalysis would facilitate new transformations that could not be achieved through simple stepwise reaction relay. This is particularly important for reactions involving slow protodeauration step. The key concerns were compatibility and orthogonal reactivity of the two catalytic systems. To explore the possibility of this new gold/radical synergistic catalysis, we selected the gold catalyzed propargyl amide cyclization as the model reaction.6 As shown in Figure 1, gold catalyst promotes the 5-exo-dig cyclization of alkyne amide 1a under mild conditions. The alkene product 2a can be isolated. Hashmi and coworkers reported the oxidation of 2a by molecular oxygen over time to give oxazole peroxide 3a.7 [Au] cat.
Radical conditions
N3
10% AgNO3
no desired products
X
O
TMSN3, 71% new
N 3b
Ph
not compatible
O Ph HN 1a
5% PPh3AuNTf2 r.t., CH3CN
OOH O Ph
N 3a
known THF, O2, 50 oC 48 h, 82%
Hashmi et al, ref 7
10% FeCl2
O Ph
2a
N
Togni reagent 55% new
CF3
O N 3c
Ph
SO2Ph 10% CuI PhSO2H, 83% Ph new
O N 3d
Figure 1. Gold catalysis and radical reaction-relay To test the reaction compatibility with gold catalyst, we explored reactions of alkene 2a with various radical species. As shown in Figure 1, new and mild radical conditions were developed for access to synthetically attractive oxazole derivatives, including azide (3b), CF3 (3c) and sulfone (3d).8 Notably, oxazole derivatives are very important building blocks in medicinal and biological research and these new strategies offered practical and efficient ways to synthesize this class of compounds.9 However, direct treatment of 1a with the combination of gold catalyst and these newly developed radical conditions gave complex reaction mixtures with no desired product observed. Clearly, the compatibility between gold catalyst and radical conditions is one crucial challenge for the development of the proposed synergistic catalysis. The recent successes in photocatalyst promoted gold redox chemistry suggested good compatibility between gold complexes and photocatalysts.10 Inspired by those results, we tested the reac-
ACS Paragon Plus Environment
Journal of the American Chemical Society
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
tivity of 1a with the combination of gold and photo catalysts under 1 atm O2. Interestingly, as shown in Figure 2A, besides the ring opening product 4a and aromatization product 4b, the oxazole-aldehyde 5a was obtained, albeit in low yield. These results suggested good compatibility of oxygen radical with gold catalyst. To improve the reaction performance, we directed our attention towards searching for other oxygen radical initiation conditions.11 As shown in Figure 2B, Fe(acac)3 was identified as the optimal catalyst (see detailed screening conditions in SI), which promoted the oxidation of 1a to oxazole-aldehyde 5a (80% conversion and 61% yield) simply with 1 atm molecular oxygen at room temperature. In addition, 18O labeled experiment confirmed that the aldehyde oxygen was originated from O2. Finally, addition of 50% tBuOOH helped the reaction to reach completion, giving 5a in 83% isolated yield, which highlighted the great compatibility of the Fe/O2 radical conditions with gold catalysis (Figure 2C). (A)
O
O
PPh3AuNTf2 (5 mol%)
Ph
[Ir] or [Ru] (2.5 mol%) Ph hv, r.t.
HN 1a
O
N H
4b
4a
conversion
4a
4b
Ir(ppy)3
100%
0%
20%
[Ir(ppy)2(bpy)]+PF6-
100%
75%
trace
0%
[Ru(bpy)3]2+
100%
33%
15%
