Letter pubs.acs.org/OrgLett
From Simple to Complex: Rhodium(III)-Catalyzed C−C Bond Cleavage and C−H Bond Functionalization for the Synthesis of 3a,8bDihydro‑1H‑cyclopenta[b]benzofuran-1-ones Guiyu Guo,§ Saihong Wan,§ Xiaodong Si, Qijian Jiang, Yuanyuan Jia, Luo Yang, and Wang Zhou*,†,‡ †
College of Chemical Engineering, Xiangtan University, Xiangtan 411105, China State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Xue Yuan Road 38, Beijing 100191, China
‡
S Supporting Information *
ABSTRACT: A rhodium(III)-catalyzed strategy for the onestep synthesis of polysubstituted cis-3a,8b-dihydro-1Hcyclopenta[b]benzofuran-1-ones from simple 2′-hydroxychalcones and alkynes is developed. This novel transformation involves a sequential C−C bond cleavage and dehydrogenative annulation, leading to the product bearing a quaternary and a tertiary carbon center. 13C labeling experiments revealed that C−C bond cleavage takes place not only at the C−C(CO) bond but also at the CC bond. This study provides an alternative strategy using C−C bond cleavage thus demonstrating the power of this strategy combined with C−H bond functionalization for assembling complex structures from simple starting materials. which the 2-pyridinyl group serves as a directing group.5 Considering the dual catalytic activities of rhodium(III) for C− C bond activation and dehydrogenative annulation, we envisioned that a rhodium(III) catalyzed reaction of readily available 2′-hydroxychalcones and alkynes would enable a direct approach toward dihydro-1H-cyclopenta[b]benzofuran-1-ones. In our design (Scheme 1), the buildup of the desired molecular skeleton could be achieved by the incorporation of
2,3,3a,8b-Tetrahydro-1H-cyclopenta[b]benzofurans are prevalent structural motifs found in numerous natural products such as Aplysin, Rocaglamide, Silvestrol, and their derivatives. Some of them exhibit a broad range of interesting and unique bioactivities (Figure 1).1 To assemble this particular molecular
Scheme 1. Strategy for Constructing Ploysubstitued cis3a,8b-Dihydro-1H-cyclopenta[b]benzofuran-1-ones
Figure 1. Representative natural products possessing tetrahydro-1Hcyclopenta[b]benzofuran core.
the alkyne moiety into the carbon skeleton of 2′-hydroxychalcones along with the formation of four new bonds via a rhodium-catalyzed sequential C−C(CO) bond cleavage and dehydrogenative annulation. A valuable product bearing both a quaternary and a tertiary carbon center will be generated in a single step manipulation. As part of our continuous efforts to develop methods for the cleavage of unstrained C−C bonds,6 we disclose herein a rhodium(III) catalyzed one-step synthesis of polysubstituted cis-3a,8b-dihydro-1H-cyclopenta[b]benzofuran-1-ones from simple starting materials. To test our hypothesis (Scheme 1), the reaction of 2′hydroxychalcone 1a with diphenyl acetylene 2a was conducted in the presence of Cp*Rh(III), silver salt, and an oxidant. Gratifyingly, the reaction was successful, giving cis-3,3a,8b-
architecture, some elegant methods have been developed such as [3 + 2] photocycloadditions,2a Nazarov cyclization,2b radical cyclization,2c,d and others,2e−g but in many of these cases several steps are required. In fact, the rapid construction of complex molecules from inexpensive and simple starting materials represents one of the greatest challenges in synthetic chemistry. Over the past few decades, transition-metal-catalyzed C−C bond activation has emerged as an active research topic because its straightforward means to restructure the carbon framework of organic compounds would provide a shortcut to molecular complexity.3 Rhodium(III) catalysis has been shown to be highly efficient in the dehydrogenative cyclization reactions, allowing the construction of cyclic/heterocyclic compounds in an atom-efficient manner.4 However, until recently, Shi and coworkers have reported the pioneering works on rhodium(III)catalyzed C−C bond cleavage of second-arylmethanols, in © 2017 American Chemical Society
Received: July 5, 2017 Published: September 11, 2017 5026
DOI: 10.1021/acs.orglett.7b02052 Org. Lett. 2017, 19, 5026−5029
Letter
Organic Letters triphenyl-3a,8b-dihydro-1H-cyclopenta[b]benzofuran-1-one (3aa) as product (Scheme 2). Its structure was later further
phenomena were also observed when chalcone 1a was reacted with a set of symmetric diaryl acetylenes (Scheme 4). The X-
Scheme 2. Scope of 2′-Hydroxychalcones Bearing Different Aromatic Substituents Groupsa,b
Scheme 4. Scope of Alkynesa,b
a
Standard reaction conditions: 1 (0.30 mmol), 2 (0.20 mmol), [(Cp*RhCl2)2] (5.0 mol %), AgSbF6 (20 mol %), Cu(OAc)2·H2O (2.0 equiv), DCE (1.5 mL) at 100 °C for 12 h under N2. bIsolated yields based on alkyne 2. The numbers in parentheses refer to the result through slow dropwise addition of the alkyne. a
Using standard reaction conditions shown in Scheme 2. bIsolated yield based on 2. Ratio of the isomers was determined by 1H NMR.
confirmed by single crystal X-ray crystallography. After extensive screening of reaction parameters including solvent, oxidant, additive, catalyst, and reaction temperature (Tables S1−S9 in the Supporting Information), the isolated yield of product 3aa was improved to 66% under the current optimum reaction conditions (see footnote of Scheme 2). With the optimized conditions in hand, 2′-hydroxychalcones bearing different aromatic substituent groups were explored, affording the corresponding dihydro-1H-cyclopenta[b]benzofuran-1ones 3 in moderate to good yields (Scheme 2). Notably, the yield in some instances could be improved slightly by slow dropwise addition of an alkyne. Importantly many of the chosen substituents offer a handle for further synthetic manipulation. Encouraged by these results, we next targeted chalcones with a variety of substituents on the ring fused aromatic ring to explore the versatility of this reaction. To our surprise, a mixture of two regioisomers were obtained as products (Scheme 3), with one isomer seemingly undergoing a C−C aryl shift. These results suggest a unique arrangement might be involved in this reaction. Moreover, similar
ray crystal structure of the mixture of (±)-3ab and (±)-3′ab further confirmed that the two isomers differ from each other with the exchanged aromatic ring on carbon atom C3a and C8b. Unusually, it appeard as if the ratio of the two isomers is not significantly related to the electronic nature of the substituents on the substrate phenyl ring. It is worth noting that the reaction predominately gave (±)-3ah as the product when 1-phenyl-1-propyne was used. It is expected other alkyl phenyl acetylenes could give similar results ((±)-3ai to (±)-3ak). In addition, some chalcones and alkynes were not compatible in this transformation (Schemes 3 and 4). To obtain insight into the reaction mechanism, isotopic labeling experiments were carried out. In 13C labeling experiments, when the carbonyl carbon C1 and alkenyl C2 of 2′-hydroxychalcone 1a were labeled, the reaction provided 3aa with labeled carbon at the C1 and C2 positions, respectively (Scheme 5, eqs 1 and 2). When chalcone 1a, with alkenyl C3 labeling, was subjected to the standard reaction conditions, a mixture of two isomers with a labeled carbon at C3 and C8b
Scheme 3. Scope with Respect to the 2′-Hydroxychalcones Componenta,b
Scheme 5. Isotopic Labelling Experiments
a
Using standard reaction conditions shown in Scheme 2. bIsolated yield based on 2. Ratio of the isomers were determined by 1H NMR. 5027
DOI: 10.1021/acs.orglett.7b02052 Org. Lett. 2017, 19, 5026−5029
Letter
Organic Letters
species would not further cyclize to give trans product due to the large strain of a 5−5 trans-fused bicyclic system. Alternatively, the oxygen atom would facilitate the isomerization of IV to VI via η-3 rhodium enolate V,10 allowing the subsequent intermolecular alkene insertion and annulation4,11 in the presence of an oxidant to furnish the final product and liberate the catalyst. Alternatively, in catalytic cycle B, intermediate II provides intermediate IX presumably via intramolecular thermal [2 + 2]12 and retro-[2 + 2]13 cycloadditions,14 followed by alkene insertion, carbonyl insertion, β-carbon elimination,15 and ketone α-C−H functionalization16 to give the isomer 3′. Even though we do not have direct evidence to verify the speculated catalytic cycles, given that the proposed mechanism is reasonable, a single product should be obtained when the aromatic ring on C3 of chalcones 1 and the aromatic rings on alkyne 2 are the same. The experimental results shown in Scheme 8 are nicely consistent with the expected outcomes.
were obtained (eq 3). By taking into account the aforementioned formation of a mixture of products, these results indicate that not only the aromatic ring but also the carbon atom connected to the aromatic ring undergo rearrangement simultaneously during the reaction, suggesting a C−C shift and not the formation of a cationic intermediate. In a deuterium labeling experiment, the reaction of the α-deuterated chalcone (1a-d) with 2a affords 3aa-d with 98% deuterium retention at the C2 position (eq 4). Then, 0.5 equiv of Rh(III) catalyst, that is equal to the stoichiometric amount of monomer Rh(III) catalyst, was used in the absence of copper acetate. The desired product was formed only in trace amount (Scheme 6). However, a 38% Scheme 6. Control Experiments
Scheme 8. Substrates Leading to Single Productsa
yield of (±)-3aa was obtained when 2.0 equiv of sodium acetate were added. Moreover, triethylamine failed to show a similar effect (for more control experiments, see Scheme S1 in the Supporting Information). Based on these preliminary results and previous studies,4 a mechanism with two catalytic cycles is proposed to rationalize the formation of the mixture of products (Scheme 7). Initially, an active Rh(III) species is generated by the reaction of [(Cp*RhCl2)2] with a silver salt and copper salt,7 followed by ligand exchange with the phenol of the chalcones and alkynes insertion to give alkenyl rhodium intermediate II.8 At this stage, two possible pathways exist concurrently. In catalytic cycle A, intermediate II undergoes an intramolecular carbonyl insertion9 and subsequent β-carbon elimination5 to afford aryl rhodium intermediate IV. Although a reversible intramolecular alkene insertion would produce intermediates VII′, in principle, this
a
The numbers in parentheses refer to the result through slow dropwise addition of alkyne.
Subjecting the product 3aa to two reductions further showed the utility of these cyclopenta[b]dihydrobenzofuran-1-ones. Pd/C and H2 reduction of product 3aa gave 4 in 55% yield while Luche reduction afforded the corresponding alcohol 5 in 73% yield (Scheme 9). In summary, we have developed a rhodium(III)-catalyzed strategy for the one-step synthesis of polysubstituted cis-3a,8bdihydro-1H-cyclopenta[b]benzofuran-1-ones from simple 2′hydroxychalcones and alkynes. This chemistry involves a tandem C−C bond cleavage and dehydrogenative annulation. To rationalize the formation of the observed products, β-carbon
Scheme 7. Proposed Mechanism
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(4) For selected recent reviews on rhodium(III)-catalyzed C−H bond fuctionalization reactions, see: (a) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (b) Satoh, T.; Miura, M. Chem. - Eur. J. 2010, 16, 11212. (c) Patureau, F. W.; Wencel-Delord, J.; Glorius, F. Aldrichimica Acta 2012, 45, 31. (d) Song, G.; Li, X. Acc. Chem. Res. 2015, 48, 1007. (e) Zhu, R.-Y.; Farmer, M. E.; Chen, Y.-Q.; Yu, J.-Q. Angew. Chem., Int. Ed. 2016, 55, 10578. (f) Gulías, M.; Mascareñas, J. L. Angew. Chem., Int. Ed. 2016, 55, 11000. (5) (a) Li, H.; Li, Y.; Zhang, X.-S.; Chen, K.; Wang, X.; Shi, Z.-J. J. Am. Chem. Soc. 2011, 133, 15244. (b) Chen, K.; Li, H.; Lei, Z.-Q.; Li, Y.; Ye, W.-H.; Zhang, L.-S.; Sun, J.; Shi, Z.-J. Angew. Chem., Int. Ed. 2012, 51, 9851. (c) Chen, K.; Li, H.; Li, Y.; Zhang, X.-S.; Lei, Z.-Q.; Shi, Z.-J. Chem. Sci. 2012, 3, 1645. (6) (a) Fan, W.; Yang, Y.; Lei, J.; Jiang, Q.; Zhou, W. J. Org. Chem. 2015, 80, 8782. (b) Zhou, W.; Fan, W.; Jiang, Q.; Liang, Y.-F.; Jiao, N. Org. Lett. 2015, 17, 2542. (c) Zhou, W.; Yang, Y.; Liu, Y.; Deng, G.-J. Green Chem. 2013, 15, 76. (7) Yang, Y.; Zhou, M.-B.; Ouyang, X.-H.; Pi, R.; Song, R.-J.; Li, J.-H. Angew. Chem., Int. Ed. 2015, 54, 6595. (8) (a) Mochida, S.; Shimizu, M.; Hirano, K.; Satoh, T.; Miura, M. Chem. - Asian J. 2010, 5, 847. (b) Seoane, A.; Casanova, N.; Quiñones, N.; Mascareñas, J. L.; Gulías, M. J. Am. Chem. Soc. 2014, 136, 834. (9) (a) Patureau, F. W.; Besset, T.; Kuhl, N.; Glorius, F. J. Am. Chem. Soc. 2011, 133, 2154. (b) Muralirajan, K.; Parthasarathy, K.; Cheng, C.-H. Angew. Chem., Int. Ed. 2011, 50, 4169. (10) (a) Shi, X.-Y.; Li, C.-J. Org. Lett. 2013, 15, 1476. (b) Dateer, R. B.; Chang, S. J. Am. Chem. Soc. 2015, 137, 4908. A base-promoted isomerization is also possible.
Scheme 9. Further Transformations of (±)-3aa
elimination of rhodium alkoxide, alkene isomerization, and intramolecular thermal [2 + 2]/retro-[2 + 2] cycloadditions of alkenyl rhodium species were proposed as the key steps. Although the efficiency and selectivity are still not satisfactory, this chemistry demonstrates the power of the concept based on merging C−C bond cleavage and C−H bond functionalization for assembling complex structures from simple starting materials. Further studies on substrate scope and mechanistic details are ongoing in our group.
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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.7b02052. Experimental procedures, analytical data for products, NMR spectra of products (PDF) Crystallographic data (CIF, CIF, CIF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected].
(11) For some representative examples of Rh(III)-catalyzed C−H activation, see: (a) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407. (b) Stuart, D. R.; Bertrand-Laperle, M.; Burgess, K. M. N.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 16474. (c) Hyster, T. K.; Rovis, T. J. Am. Chem. Soc. 2010, 132, 10565. (d) Song, G.; Chen, D.; Pan, C.-L.; Crabtree, R. H.; Li, X. J. Org. Chem. 2010, 75, 7487. (e) Rakshit, S.; Patureau, F. W.; Glorius, F. J. Am. Chem. Soc. 2010, 132, 9585. (f) Xu, H.-J.; Lu, Y.; Farmer, M. E.; Wang, H.-W.; Zhao, D.; Kang, Y.-S.; Sun, W.-Y.; Yu, J.-Q. J. Am. Chem. Soc. 2017, 139, 2200. (12) (a) Alcaide, B.; Almendros, P.; Aragoncillo, C. Chem. Soc. Rev. 2010, 39, 783. (b) Shen, T.; Zhang, Y.; Liang, Y.-F.; Jiao, N. J. Am. Chem. Soc. 2016, 138, 13147. (13) For example: Troadec, T.; Lopez Reyes, M.; Rodriguez, R.; Baceiredo, A.; Saffon-Merceron, N.; Branchadell, V.; Kato, T. J. Am. Chem. Soc. 2016, 138, 2965. (14) [2 + 2]/retro-[2 + 2] cycloaddition are well-known processes in olefin metathesis reaction; see: (a) Fürstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012. (b) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18. (c) Schrock, R. R.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2003, 42, 4592. (15) For rhodium(I)-catalyzed retro-allylations of norbornenols, see: Waibel, M.; Cramer, N. Chem. Commun. 2011, 47, 346. (16) Tan, X.; Liu, B.; Li, X.; Li, B.; Xu, S.; Song, H.; Wang, B. J. Am. Chem. Soc. 2012, 134, 16163−16166.
ORCID
Wang Zhou: 0000-0001-8629-086X Author Contributions §
G.G. and S.W. contributed equally.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS Financial support from NSFC (21372188) and the State Key Laboratory of Natural and Biomimetic Drugs are greatly appreciated. We thank Prof. Qingjiang Li at Sun Yat-sen University, Prof. Zhuangzhi Shi at Nanjing University, and Prof. Scott Stewart at the University of Western Australia for helpful discussions and suggestions.
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REFERENCES
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