Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
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Fe-Catalyzed Cycloisomerization of Aryl Allenyl Ketones: Access to 3‑Arylidene-indan-1-ones Johannes Teske and Bernd Plietker* Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, DE-70569 Stuttgart, Germany S Supporting Information *
ABSTRACT: A cycloisomerization of aryl allenyl ketones to 3-arylidene-indan-1-ones using a cationic Fe-complex as a catalyst is reported. The catalyst opens a synthetically interesting reaction pathway to this surprisingly underrepresented class of indanones that are not accessible using alternative catalytic systems.
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n sharp contrast to 2-alkylidene- or -arylidene-indan-1-ones,1 the 3-alkylidene- or -arylidene-indan-1-ones are underrepresented structural motifs in organic chemistry. Within the context of a total synthesis we were looking for an efficient strategy to synthesize 3-arylidene-indanon-1-ones and were surprised to find that only a handful of methods exist, which require multistep sequences.2 We speculated that a cycloisomerization of aryl allenyl ketones could fill this lack of methods; however, catalytic activation of such substrates leads to the clean formation of densely substituted furans as pioneered by the group of Gevorgyan (Scheme 1).3 Most recently and while this work was in progress, the group of Ren was able to demonstrate that the cycloisomerization of αsubstituted aryl allenyl ketones might indeed result in the formation of the corresponding α-substituted arylideneindanones under harsh conditions (DMSO, 160 °C).4 However, side reactions such as π-bond migration to the corresponding indenones and low yields for substrates lacking the α-substituent limit the applicability (Scheme 1). Recently, we reported the use of the cationic 16-electron Fe(0)-complex [(Ph3P)2Fe(CO)(NO)]BF4 1 as a π-Lewis acid catalyst for the redox-neutral cycloisomerization of enyne acetates.5 Based on these results we speculated that this Fe-complex might be able to alter the catalytic pathway described by Gevorgyan via activation of the electron-poor CαCβ bond. This would pave the way for a redox-neutral cycloisomerization leading to products of a formal olefin hydroarylation reaction. Herein we report the successful realization of this concept. Catalytic amounts of the aforementioned cationic Fe(0)nitrosyl complex allow the mild cycloisomerization of aryl allenyl ketones to the corresponding 3-arylidene-indan-1-ones © XXXX American Chemical Society
Scheme 1. Cycloisomerization of Aryl Allenyl Ketones: State of the Art and This Work
with a good substrate scope and functional group tolerance. In sharp contrast to the use of catalytic amounts of Lewis or Received: February 20, 2018
A
DOI: 10.1021/acs.orglett.8b00612 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Brønsted acids, no substituted furans or π-bond migration products were observed. Based on our previous work, we initiated this study by employing aryl allenyl ketone 2 to the conditions that proved successful in the cycloisomerization of enyne acetates and observed a clean cycloisomerization of 2 to the corresponding indanone 3 in moderate yield (Table 1, entry 1).
Scheme 2. Fe-Catalyzed Cycloisomerization
Table 1. Catalyst Screeninga
entry 1 2 3e 4 5 6 7 8 9 10 11
3b/4b
catalyst 1 − − HBF4·OEt2 TMSOTf AuCl3 PtCl2 (o-Ph)C6H4PtBu2)Au(CH3CN)SbF6 (PPh3)AuCl, AgBF4 (PPh3)AuCl AgBF4
quantitative conversion and isolated yields up to 93% (entries 1−8, Table 2). In the case of meta-substitution, product 20 was formed as a single isomer (entry 9, Table 2). Substitution in the ortho position leads to the decreased reactivity of the starting materials (entry 10, Table 2); however, this effect can be overcome through substitution in the meta- or para-position as exemplified for the cycloisomerization of highly decorated allene 23 to arene 24, which is being formed in a quantitative fashion (entry 11, Table 2). In the case of nonidentical substituents at C3 of the allene moiety, a high degree of (Z)/ (E)-selectivity up to 7.5/1 was observed (entries 12−14, Table 2). Substitution in the α-position significantly increased the reactivity, leading to mostly quantitative isolation of the cycloisomerization products (entries 15−17, Table 2). While ortho substitution was of no hindrance now, even a terminal allene 37 could be transformed to the corresponding product 38 albeit in moderate yields (entry 18, Table 2). In contrast to oxophilic Lewis acid catalysts, acyl residues in the α-position could not increase the overall yield of the corresponding products 42 and 44 (entries 20 and 21, Table 2).8 In no case was π-bond isomerization to the corresponding endocyclic indenone products or furan formation observed; even allene 45, which under thermal conditions undergoes cycloisomerization and subsequent π-bond migration to the corresponding indenones, reacted to indanone 46 selectively (entry 22, Table 2). At the outset of this project we envisioned coordination of the cationic Fe-complex to the C−C π-bond to alter the reaction pathway;9 hence, steric hindrance close to the carbonyl group should not have a pronounced effect on the conversion (Scheme 3). In order to test this hypothesis, o-methoxy- and o-isopropoxy aryl allenyl ketones 47 and 49 were prepared and subjected to the reaction conditions. The corresponding indanones 48 and 50 were isolated in quantitative yields (eqs 1 and 2, Scheme 3). In a competition experiment both 47 and 49 were reacted using catalyst 1. The reaction was stopped after 30 min, and the conversion to 48 and 50, respectively, was analyzed. Sterically more hindered aryl allenyl ketone 47 reacted even faster, a result that might reflect the better stabilization of intermediate carbocations formed within the reaction (eq 3, Scheme 3). In a final experiment, aldol products 51 and 53 were treated with catalyst 1 under the established reaction conditions. In both cases the Fe-catalyzed cycloisomerization took place; however, the primary formed product underwent fast elimination to the corresponding 1,3-dienes 52, 54 or a retro-aldol reaction with formation of indanone 3 in 14% or even 47% yield, respectively (eq 4, Scheme 3). Herein we report an unprecedented metal-catalyzed cycloisomerization of aryl allenyl ketones to 3-aryliden or 3alkylidene-indan-1-ones. The cationic Fe(0)-nitrosyl complex [(Ph3P)2Fe(CO)(NO)]BF4 1 is able to alter the reported Lewis acid catalyzed pathway in favor of the cycloisomerization route to give indanones rather than furans. Good functional
c
67% :0% (5%:0%)d − 11% 29%c:0% 8%:41% − − 0%:76% 49%:0% − 47%:0%
a
Reaction conditions: All reactions were performed on a 0.2 mmol scale using 10 mol % of the catalyst in dry dichloromethane (1 mL) at 50 °C under a N2 atmosphere in a sealed tube for 22 h. bYield obtained through 1H NMR-integration using 1,3,5-trimethoxybenzene as internal standard. cIsolated yield. dThe reaction was performed at room temperature. eThe reaction was performed at 160 °C in DMSO (0.1 M).
Importantly, the expected furan 4 was not formed under these conditions. While the blank reaction did not produce any product (Table 1, entry 2), application of Ren’s conditions mainly caused decomposition of the starting material (Table 1, entry 3). Control experiments using HBF4 led to the formation of indanone 3 (Table 1, entry 4), and TMSOTf led to the formation of furan 4 along with minor quantities of indanone 3 (Table 1, entry 5). Whereas neither AuCl3 nor PtCl2 showed any activity (Table 1, entries 6 and 7), a combination of (Ph3P)AuCl and AgBF4 induced the formation of indanone 3 in moderate yields (Table 1, entry 9). However, as it turned out AgBF4 was the active catalyst (Table 1, entry 11). (Ph3P)AuCl did not show any catalytic activity (Table 1, entry 10). In sharp contrast, Echavarren’s Au(+I)-catalyst was catalytically active, yet, clean formation of furan 4 was observed (Table 1, entry 8). Careful optimization of different reaction parameters6 indicated a concentration of 0.1 M in 1,2-dichloroethane (1,2-DCE) and a temperature of 60 °C to be optimal which results in the clean formation of product 3 in 83% isolated yield after 8 h of reaction time using 5 mol % complex 1 (Scheme 2).7 With these optimized conditions in hand, we set out to analyze the scope and limitations (Table 2). The reaction proved to be broadly applicable, both electron-rich and -poor ortho-, meta-, and para-substituted aromatic moieties are reactive. As expected, the substitution pattern at the aromatic moiety had a profound influence on the conversion rate. paraSubstituents known to stabilize positive charge result in almost B
DOI: 10.1021/acs.orglett.8b00612 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters Table 2. Scope and Limitationsa,b
Scheme 3. Test Experiments
catalysis and adds an interesting feature to the steadily growing area of base metal catalysis.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b00612. Experimental procedures for preparation of starting materials and products, full characterization of all reported compounds, 1H NMR spectra, 13C NMR spectra, IR spectra, HRMS (PDF) Accession Codes
CCDC 1818815−1818817 and 1818819 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/ cif, or by emailing
[email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Bernd Plietker: 0000-0001-8423-6173 Notes a
The authors declare no competing financial interest.
Reaction conditions: All reactions were performed on a 0.5 mmol scale using 5 mol % of the catalyst 1 in dry 1,2-dichloroethane (5 mL) at 60 °C under a N2-atmosphere in a sealed tube for 8 h. bIsolated yield. c(Z)/(E) ratio given in parentheses.
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ACKNOWLEDGMENTS Dedicated to Prof. Jan-Erling Bäckvall (Stockholm University) on the occasion of his 70th birthday. The authors are grateful to the Deutsche Forschungsgemeinschaft for financial support, Dr. Wolfgang Frey (Universität Stuttgart) for X-ray analysis, and
group tolerance and a broad application range are characteristic of this method. This novel reactivity opens a new field in FeC
DOI: 10.1021/acs.orglett.8b00612 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters Marina Fuhrer (Universität Stuttgart) for assistance in the starting material synthesis.
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REFERENCES
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DOI: 10.1021/acs.orglett.8b00612 Org. Lett. XXXX, XXX, XXX−XXX
