Letter Cite This: Org. Lett. 2018, 20, 4504−4506
pubs.acs.org/OrgLett
Synthetic Studies of the Daphniphyllum Alkaloids: A Cooperative Reaction of Proximal Functional Groups Forming a Tetracyclic System Ryosuke Yamada, Tohru Fukuyama, and Satoshi Yokoshima* Org. Lett. 2018.20:4504-4506. Downloaded from pubs.acs.org by UNIV OF CALIFORNIA SANTA BARBARA on 08/04/18. For personal use only.
Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan S Supporting Information *
ABSTRACT: During the course of synthetic studies of the Daphniphyllum alkaloids, an unusual reaction of a rhodium carbenoid was observed. The bicyclic substrate, in which an α-diazo-β-ketoester moiety was present at the 3-position of a 1,4-diene moiety, was treated with rhodium pivalate to produce an intermediate having diene and ketene moieties. This intermediate underwent an intramolecular [4 + 2] cycloaddition reaction to form a tetracyclic compound.
D
Scheme 1. Synthetic Strategy toward the Daphniphyllum Alkaloids
uring the synthesis of complicated molecules, such as natural products, reactions tend to be conducted under a variety of unusual circumstances. Often, the reactions do not give the expected products because neighboring functional groups disrupt the desired transformations. To avoid the fruitless side reactions, the structures of the substrates or the reaction conditions would have to be finely tuned to establish the appropriate solutions. Sometimes, reactions under unusual situations afford unexpected, but constructive products. For example, cooperative reactions of proximal functional groups can form unusual structures. Herein, we disclose an unexpected reaction found during the course of our synthetic studies of the Daphniphyllum alkaloids (Figure 1).1,2
prepared via a pinacol-type rearrangement (Scheme 2). Addition of allyl alcohol unit 45 to the known enone 36 afforded diol 5, which was converted into epoxide 6 in a threestep sequence involving oxidation of an allylic alcohol moiety with MnO2, nucleophilic epoxidation, and reduction with sodium borohydride.7 Sequential protection of the primary and then tertiary hydroxy groups in 6 with TIPS and TMS groups, respectively, gave 7. Upon treatment with TiCl4 in dichloromethane, 7 underwent a pinacol-type rearrangement via cleavage of the oxirane ring to form a tertiary cation and subsequent 1,2-shift of the alkenyl group to furnish [7−5] bicyclic compound 8 as the major product.8,9 After protecting the hydroxy group with a pivaloyl group, the ketone moiety was converted into an enol triflate, which was subjected to Pdcatalyzed cross-coupling with trimethylindium to give 9.10 Reductive cleavage of the pivaloyl group in 9 with DIBAL, followed by oxidation of the resulting primary alcohol, afforded
Figure 1. Structures of selected Daphniphyllum alkaloids.
One of our synthetic strategies toward the Daphniphyllum alkaloids involved an intramolecular C−H insertion reaction of 1 at an allylic position to form [7−5−5] tricyclic compound 23 containing a quaternary carbon and two contiguous stereogenic centers adjacent to a tetrasubstituted C−C double bond (Scheme 1).4 To test this idea, the requisite substrate was first © 2018 American Chemical Society
Received: June 9, 2018 Published: July 18, 2018 4504
DOI: 10.1021/acs.orglett.8b01800 Org. Lett. 2018, 20, 4504−4506
Letter
Organic Letters Scheme 2. Preparation of the α-Diazo-β-ketoester 11
tected alcohol were not crystalline, but the NMR spectra were consistent with the structure shown in Scheme 3. The proposed reaction mechanism is shown in Scheme 4. Under these conditions, the diazo moiety reacted with a Scheme 4. Proposed Reaction Mechanism
rhodium catalyst to form rhodium carbenoid 15, which underwent cyclopropanation to give 16, an intermediate having a bicyclo[2.1.0]pentanone system.13 Fragmentation of the strained cyclobutanone ring in 16 occurred to form an intermediate 17 containing a diene and a ketene moiety. An intramolecular [4 + 2] cycloaddition between these moieties produced 12. Reactions of a ketene with a cyclic 1,3-diene would usually produce a cyclobutanone, presumably via [4 + 2] cycloaddition between the 1,3-diene and the carbonyl group in the ketene, followed by a [3,3]-sigmatropic rearrangement of the resulting intermediate.14 In our case, this reaction pathway was inhibited due to the structural constraint. Instead, an unusual [4 + 2] cycloaddition between the 1,3-diene and the C−C double bond in the ketene moiety occurred.15 The reaction of the rhodium carbenoid 15 at the other C−C double bond generated the minor product 13 by way of the same sequence.16 In conclusion, we found that a rhodium carbenoid reacted with a neighboring C−C double bond to produce an intermediate containing a diene and a ketene moiety. This intermediate underwent an intramolecular [4 + 2] cycloaddition reaction to form an unusual tetracyclic compound.
aldehyde 10, to which was added a lithium enolate derived from methyl acetate. Oxidation of the resulting secondary alcohol gave the β-ketoester, which was reacted with ADMP to afford α-diazo-β-ketoester 11.11 Treatment of 11 with Rh2(OPiv)4 in benzene at 40 °C smoothly consumed the substrate, but did not produce the desired [7−5−5] tricyclic compound. Instead, we isolated the tetracyclic compounds 12 and 13 in 63% and 24% yields, respectively (Scheme 3).12 The structure of 12 was initially deduced on the basis of the NMR spectrum and then unambiguously confirmed by X-ray crystallography of the desilylated compound 14. Unfortunately, 13 and its depro-
■
Scheme 3. Unexpected Reaction of Rhodium Carbenoid
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b01800. Experimental procedures, characterization for new compounds, including 1H and 13C NMR spectra (PDF) Accession Codes
CCDC 1839230 contains 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. 4505
DOI: 10.1021/acs.orglett.8b01800 Org. Lett. 2018, 20, 4504−4506
Letter
Organic Letters
■
(b) Baldwin, S. W.; Chen, P.; Nikolic, N.; Weinseimer, D. C. Org. Lett. 2000, 2, 1193. (c) Marson, C. M.; Khan, A.; Porter, R. A.; Cobb, A. J. A. Tetrahedron Lett. 2002, 43, 6637. (d) Zhang, X.-M.; Tu, Y.-Q.; Zhang, F.-M.; Shao, H.; Meng, X. Angew. Chem., Int. Ed. 2011, 50, 3916. (e) Zhang, X.-M.; Shao, H.; Tu, Y.-Q.; Zhang, F.-M.; Wang, S.H. J. Org. Chem. 2012, 77, 8174. (9) The pinacol-type rearrangement proceeded with a 4:1 selectivity, producing an inseparable mixture of 8 and its isomer 18.
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Tohru Fukuyama: 0000-0001-9612-5665 Satoshi Yokoshima: 0000-0003-4036-0062 Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS This work was financially supported by JSPS KAKENHI (Grant Numbers 16H01141 and 17H01523), by the Takeda Science Foundation, and by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research; BINDS) from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP17am0101099.
■
(10) (a) Pérez, I.; Sestelo, J. P.; Sarandeses, L. A. Org. Lett. 1999, 1, 1267. (b) Pérez, I.; Sestelo, J. P.; Sarandeses, L. A. J. Am. Chem. Soc. 2001, 123, 4155. (11) (a) Kitamura, M.; Tashiro, N.; Okauchi, T. Synlett 2009, 2009, 2943. (b) Kitamura, M.; Tashiro, N.; Miyagawa, S.; Okauchi, T. Synthesis 2011, 2011, 1037. (12) Using Rh2(OTFA)4 as a catalyst or 1,2-dichloroethane as a solvent did not induce dramatic changes in the results, giving 12 as the major product and 13 in good yields. (13) (a) Smith, A. B., III J. Chem. Soc., Chem. Commun. 1974, 695. (b) Lokensgard, J. P.; O’dea, J.; Hill, E. A. J. Org. Chem. 1974, 39, 3355. (c) Zimmerman, H. E.; Little, R. D. J. Am. Chem. Soc. 1974, 96, 4623. (d) Smith, A. B., III; Toder, B. H.; Branca, S. J. J. Am. Chem. Soc. 1976, 98, 7456. (e) Branca, S. J.; Lock, R. L.; Smith, A. B., III J. Org. Chem. 1977, 42, 3165. (f) Smith, A. B., III; Toder, B. H.; Branca, S. J. J. Am. Chem. Soc. 1984, 106, 3995. (g) Smith, A. B., III; Toder, B. H.; Richmond, R.; Branca, S. J. J. Am. Chem. Soc. 1984, 106, 4001. (h) Ceccherelli, P.; Curini, M.; Marcotullio, M. C.; Rosati, O. Gazz. Chim. Ital. 1994, 124, 177. (i) Ceccherelli, P.; Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O. Synth. Commun. 1995, 25, 301. (14) (a) Yamabe, S.; Dai, T.; Minato, T.; Machiguchi, T.; Hasegawa, T. J. Am. Chem. Soc. 1996, 118, 6518. (b) Machiguchi, T.; Yamabe, S. Yuki Gosei Kagaku Kyokaishi 1997, 55, 56. (c) Machiguchi, T.; Hasegawa, T.; Ishiwata, A.; Terashima, S.; Yamabe, S.; Minato, T. J. Am. Chem. Soc. 1999, 121, 4771. (15) Mayr, H.; Heigl, U. W. J. Chem. Soc., Chem. Commun. 1987, 1804. (16) The selectivity of the reaction of the rhodium carbenoid 15 might be explained with the electron richness of the C−C double bonds. For Hammett studies on cyclopropanation of rhodium carbenoids, see Davies, H. M. L.; Panaro, S. A. Tetrahedron 2000, 56, 4871.
REFERENCES
(1) (a) Kobayashi, J.; Kubota, T. Nat. Prod. Rep. 2009, 26, 936. (b) Kang, B.; Jakubec, P.; Dixon, D. J. Nat. Prod. Rep. 2014, 31, 550. (c) Chattopadhyay, A. K.; Hanessian, S. Chem. Rev. 2017, 117, 4104. (2) (a) Heathcock, C. H.; Davidsen, S. K.; Mills, S.; Sanner, M. A. J. Am. Chem. Soc. 1986, 108, 5650. (b) Ruggeri, R. B.; Hansen, M. M.; Heathcock, C. H. J. Am. Chem. Soc. 1988, 110, 8734. (c) Ruggeri, R. B.; Mcclure, K. F.; Heathcock, C. H. J. Am. Chem. Soc. 1989, 111, 1530. (d) Piettre, S.; Heathcock, C. H. Science 1990, 248, 1532. (e) Ruggeri, R. B.; Heathcock, C. H. J. Org. Chem. 1990, 55, 3714. (f) Stafford, J. A.; Heathcock, C. H. J. Org. Chem. 1990, 55, 5433. (g) Heathcock, C. H.; Stafford, J. A.; Clark, D. L. J. Org. Chem. 1992, 57, 2575. (h) Heathcock, C. H.; Kath, J. C.; Ruggeri, R. B. J. Org. Chem. 1995, 60, 1120. (i) Weiss, M. E.; Carreira, E. M. Angew. Chem., Int. Ed. 2011, 50, 11501. (j) Lu, Z.; Li, Y.; Deng, J.; Li, A. Nat. Chem. 2013, 5, 679. (k) Shvartsbart, A.; Smith, A. B., III J. Am. Chem. Soc. 2014, 136, 870. (l) Shvartsbart, A.; Smith, A. B., III J. Am. Chem. Soc. 2015, 137, 3510. (m) Yamada, R.; Adachi, Y.; Yokoshima, S.; Fukuyama, T. Angew. Chem., Int. Ed. 2016, 55, 6067. (n) Li, J.; Zhang, W.; Zhang, F.; Chen, Y.; Li, A. J. Am. Chem. Soc. 2017, 139, 14893. (o) Shi, H.; Michaelides, I. N.; Darses, B.; Jakubec, P.; Nguyen, Q. N. N.; Paton, R. S.; Dixon, D. J. J. Am. Chem. Soc. 2017, 139, 17755. (p) Chen, X.; Zhang, H.-J.; Yang, X.; Lv, H.; Shao, X.; Tao, C.; Wang, H.; Cheng, B.; Li, Y.; Guo, J.; Zhang, J.; Zhai, H. Angew. Chem., Int. Ed. 2018, 57, 947. (q) Chen, Y.; Zhang, W.; Ren, L.; Li, J.; Li, A. Angew. Chem., Int. Ed. 2018, 57, 952. (r) Zhang, W.; Ding, M.; Li, J.; Guo, Z.; Lu, M.; Chen, Y.; Liu, L.; Shen, Y.-H.; Li, A. J. Am. Chem. Soc. 2018, 140, 4227. (3) (a) Doyle, M. P.; Duffy, R.; Ratnikov, M.; Zhou, L. Chem. Rev. 2010, 110, 704. (b) Taber, D. F.; Ruckle, R. E. J. Am. Chem. Soc. 1986, 108, 7686. (c) Hirooka, Y.; Ikeuchi, K.; Kawamoto, Y.; Akao, Y.; Furuta, T.; Asakawa, T.; Inai, M.; Wakimoto, T.; Fukuyama, T.; Kan, T. Org. Lett. 2014, 16, 1646. (d) Kan, T.; Asakawa, T.; Inai, M. Heterocycles 2016, 92, 31. (4) Kitabayashi, Y.; Fukuyama, T.; Yokoshima, S. Org. Biomol. Chem. 2018, 16, 3556. (5) (a) Sakakura, A.; Takayanagi, Y.; Kigoshi, H. Tetrahedron Lett. 2002, 43, 6055. (b) Suenaga, K.; Takayanagi, Y.; Yamaura, M.; Kigoshi, H. Chem. Lett. 2004, 33, 918. (c) Miyake, T.; Kigoshi, H.; Akita, H. Tetrahedron: Asymmetry 2007, 18, 2915. (6) Lange, G. L.; Hall, T.-W. J. Org. Chem. 1974, 39, 3819. (7) In an attempted epoxidation directed by a hydroxy group in 5, the tetrasubstituted C−C double bond also reacted to produce a mixture of mono- and bis-epoxide. (8) (a) Maruoka, K.; Hasegawa, M.; Yamamoto, H.; Suzuki, K.; Shimazaki, M.; Tsuchihashi, G. J. Am. Chem. Soc. 1986, 108, 3827. 4506
DOI: 10.1021/acs.orglett.8b01800 Org. Lett. 2018, 20, 4504−4506
