Remote Asymmetric Bromination Reaction with Vinylketene Silyl N,O

Letter pubs.acs.org/OrgLett

Remote Asymmetric Bromination Reaction with Vinylketene Silyl N,O‑Acetal and Its Application to Total Synthesis of Pellasoren A Shinji Sekiya, Mao Okumura, Kei Kubota, Tatsuya Nakamura, Daisuke Sekine, and Seijiro Hosokawa* Department of Applied Chemistry, Faculty of Science and Engineering, Waseda University 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan S Supporting Information *

ABSTRACT: Stereoselective bromination of the E,E-vinylketene silyl N,Oacetal possessing a chiral auxiliary has been achieved and applied to introduction of heteroatom at γ-position of α,β-unsaturated imide. The reactions proceeded in high stereoselectivity. Total synthesis of pellasoren A, an antitumor propionate from the myxobacteriun Sorangium cellulosum, has been accomplished in short steps by this methodology and our method of reduced polypropionate synthesis.

R

Scheme 2. Remote Asymmetric Bromination of Silyl Dienol Ether 1

emote asymmetric induction reactions have been investigated as a challenging matter in organic chemistry.1 Although only a limited number of these reactions are practical, remote asymmetric induction reactions have been powerful methods in natural product synthesis.2 During the course of our research on methodologies and strategies for short step synthesis of polypropionates, we have developed remote asymmetric induction reactions using the E,E-enolate 1 (Scheme 1).3 The vinylogous Mukaiyama aldol reaction with

Table 1. Remote Asymmetric Bromination Using Lewis Acid Scheme 1. Remote Asymmetric Induction Reactions Using the Vinylogous Mukaiyama Aldol Reaction

1 performed both construction of stereogenic centers at C4 and C5 positions and introduction of α,β-unsaturated carbonyl chain. Therefore, this reaction has been used widely in natural product synthesis.4 Recently, we have developed analogous reactions with 1 including syn-selective vinylogous Mukaiyama aldol reactions,5 acylation reaction,6 and alkylation reaction.7 All of these reactions afforded adducts possessing the same stereochemistry at C4 position. In this paper, we present the remote asymmetric bromination with 1, which produces the opposite stereochemistry to heretofore reactions (Scheme 2). This reaction is useful to introduce a heteroatom at γ-position of α,β-unsaturated imide. Application of this method to natural product synthesis is also revealed. At first, we performed bromination with silyl N,O-ketene acetal 1 (Table 1). Bromine promoted the reaction in the absence of any additive to give products 3 and 4-epi-3 as a © 2017 American Chemical Society

entry

Lewis acid

yield (%)

dra (3/4-epi-3)

1 2b 3b 4b 5b 6b 7b 8c

TMSOTf SnCl4 TiCl4 BF3·OEt2 n-Bu2BOTf BCl3 BCl3

95 97 93 86 96 74 91 90

3.0:1 1.8:1 6.0:1 >20:1 3.1:1 7.5:1 >20:1 3.9:1

a Determined by 400 MHz 1H NMR. bBr2 was added into the mixture of 1 and Lewis acid. cCompound 1 was added into the mixture of Br2 and Lewis acid.

diastereo mixture in a ratio of 3:1 (Table 1, entry 1). The major product was isolated as a single crystal to allow X-ray crystallography and was found to be in the 4R configuration Received: March 28, 2017 Published: April 21, 2017 2394

DOI: 10.1021/acs.orglett.7b00920 Org. Lett. 2017, 19, 2394−2397

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Organic Letters

repulsion with the isopropyl group. On the other hand, bromination reactions gave 3 as the major isomer, which indicated that the reactions proceeded from the upper side of the diene. In the case of bromination without Lewis acid (Table 1, entry 1), electric repulsion between bromine and the carbonyl oxygen of the oxazolidone made the attack from the upper side was preferred, and 4R product 3 was obtained as the major product. In the bromination reaction with Lewis acid, Lewis acid was coordinated with the carbonyl oxygen of the chiral auxiliary to interfere with the approach of the electrophile from the lower face of the diene. Therefore, bromine reacted from the upper face of the diene (TS-2), which provided 3 possessing the 4R configuration. This transition state was supported by the results of entries 7 and 8 in Table 1. With the chiral allylic bromide in hand, derivatization reactions to introduce heteroatoms have been examined (Scheme 3). Azide was substituted with bromide smoothly in

(Figure 1). Next, we examined the effect of Lewis acid (Table 1, entries 2−7).

Figure 1. ORTEP drawing of bromide 3.

Although addition of TMSOTf did not show improvement of the reaction, SnCl4 gave better selectivity (entries 2 and 3). When TiCl4 was employed, the reaction provided 3 in good yield with excellent stereoselectivity (entry 4). BF3·OEt2 and nBu2BOTf afforded products with moderate stereoselectivity (entries 5 and 6). However, addition of BCl3 improved the stereoselectivity dramatically, and bromide 3 was produced as a single isomer in high yield (entry 7). The order of addition of reagents was very important. Addition of Br2 into the mixture of silyl N,O-ketene acetal 1 and BCl3 provided 3 in excellent selectivity (entry 7), while addition of 1 into the mixture of Br2 and BCl3 gave only the moderate selectivity (entry 8). The product 3 had the opposite stereochemistry at the C4 position compared to the product of previous reactions (Scheme 1), which indicated that the bromination proceeded in a stereoselective manner different from those reactions. Based on these results, we propose the reaction mechanism of this reaction (Figure 2). In prvious reactions including the vinylogous Mukaiyama aldol reaction, electrophile approached from the lower face of the diene (TS-1) to avoid steric

Scheme 3. Substitution Reactions to Introduce a Heteroatom at the γ-Position

the presence of crown ether. The reaction proceeded stereospecifically to give 5 with inverted stereochemistry at the γ position in excellent yield. Acetate and thioacetate were also introduced in the presence of crown ether to afford 6 and 7, respectively. In the absence of crown ether, each reaction showed partially epimerization to give a diastereo- mixture of substituted products, which indicated the bromide ion, generated by partial reaction, reacted with allylic bromide 3 to give epimerized bromide. Establishing the stereoselective synthesis of γ-heteroatomsubstituted α,β-unsaturated imide, application to a short step synthesis of natural product was planned. Pellasoren A (8, Scheme 4) was isolated from the myxobacteriun Sorangium cellulosum and reported as an antitumor agent. This compound has been synthesized, and the absolute structure was determined by the Kallesse group.8 The bioactivity and structure of pellasoren A have indicated potential for new anticancer compounds. Herein, we present a concise synthesis of pellasoren A using our methodologies. Our synthetic plan of pellasoren A is disclosed in Scheme 4. The target molecule 8 was divided into two segments, amide segment 9 and lactone segment 10. Amide segment 9 would be synthesized by coupling of carboxylic acid 118 and amine 12, which might be derived from azide 5. On the other hand, lactone segment 10 would be synthesized by our reduced propionate synthesis

Figure 2. Proposed transition state of the bromination reaction. 2395

DOI: 10.1021/acs.orglett.7b00920 Org. Lett. 2017, 19, 2394−2397

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Organic Letters Scheme 4. Synthetic Plan of Pellasoren A Using Remote Asymmetric Induction Reactions

Scheme 6. Synthesis of Lactone Segment 10

the resulting enolate was protonated in a stereoselective manner by using 187 as a bulky proton source. The crude product including α,β-saturated imide was treated under the acidic conditions to afford lactone segment 10. Thus, an efficient and short-step synthesis of 10 has been accomplished. Finally, olefin metathesis between 9 and 10 gave pellasoren A (8) as a single isomer (Scheme 7). Spectral data of synthetic 8 were identical with those of natural product in all aspects.8

using asymmetric vinylogous Mukaiyama aldol reaction with vinylketene silyl N,O-acetal 1.9 Synthesis of amide segment 9 is shown in Scheme 5. Treatment of azide 5, prepared by using remote asymmetric Scheme 5. Synthesis of Amide Segment 9

Scheme 7. Completion of Total Synthesis of Pellasoren A (8)

In conclusion, we established the stereoselective bromination reaction using vinylketene silyl N,O-acetal 1. The remote asymmetric bromination reaction proceeded with the opposite face selectivity of previous reactions of 1. The product of this reaction was derived to substitution with nitrogen, oxygen, and sulfur atoms. Additionally, we applied this methodology to the total synthesis of pellasoren A (8), and a concise synthesis, achieved in six steps of the longest linear sequence from silyl N,O-acetal 1, has been established.

halogenation reaction as mentioned above, with triphenylphosphine in the presence of water gave the corresponding amine, which was immediately acylated in situ with 11 to yield amide 14. Reduction of the imide moiety of 14 with DIBAL afforded aldehyde 15 in high yield. Aldehyde 15 was submitted to the subsequent allylation and Peterson olefination by reacting with the allylborane prepared with allene 16 and 9-BBN.10 The reaction proceeded smoothly and stereoselectively to give amide segment 9 directly. On the other hand, synthesis of lactone segment 10 was accomplished by our reduced polypropionate synthesis (Scheme 6).9 The vinylogous Mukaiyama aldol reaction using dienolate 1 with aldehyde 13 proceeded to give adduct 17 in high yield with high stereoselectivity.8 Treatment of 17 with sodium in liquid ammonia promoted the Birch reduction, and

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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.7b00920. X-ray data for compound 3 (CIF) X-ray data for compound 7 (CIF) Experimental procedures, spectral data of compounds, and 1H and 13C NMR spectra (PDF) 2396

DOI: 10.1021/acs.orglett.7b00920 Org. Lett. 2017, 19, 2394−2397

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(6) Takahashi, Y.; Otsuka, M.; Harachi, M.; Mukaeda, Y.; Hosokawa, S. Org. Lett. 2014, 16, 4106. (7) Nakamura, T.; Kubota, K.; Ieki, T.; Hosokawa, S. Org. Lett. 2016, 18, 132. (8) Jahns, C.; Hoffmann, T.; Müller, S.; Gerth, K.; Washausen, P.; Höfle, G.; Reichenbach, H.; Kalesse, M.; Müller, R. Angew. Chem., Int. Ed. 2012, 51, 5239. (9) Nakamura, T.; Harachi, M.; Kano, T.; Mukaeda, Y.; Hosokawa, S. Org. Lett. 2013, 15, 3170. (10) Wang, K. K.; Liu, C.; Gu, Y. G.; Burnett, F. N.; Sattsangi, P. D. J. Org. Chem. 1991, 56, 1914.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Seijiro Hosokawa: 0000-0002-8036-532X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful for financial support from The Kurata Memorial Hitachi Science and Technology Foundation, The Naito Foundation, and The Sumitomo Foundation.

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REFERENCES

(1) (a) Breslow, R.; Corcoran, R. J.; Snider, B. B. J. Am. Chem. Soc. 1974, 96, 6791. (b) Still, W. C.; Darst, K. P. J. Am. Chem. Soc. 1980, 102, 7385. (c) Hauser, F. M.; Ellenberger, S. R.; Clardy, J. C.; Bass, L. S. J. Am. Chem. Soc. 1984, 106, 2458. (d) Molander, G. A.; Bobbitt, K. L. J. Am. Chem. Soc. 1993, 115, 7517. (e) Linnane, L. P.; Magnus, N.; Magnus, P. Nature 1997, 385, 799. (f) Clayden, J.; Lund, A.; Vallverdú, L.; Helliwell, M. Nature 2004, 431, 966. (g) Byrne, L.; Solà, J.; Boddaert, T.; Marcelli, T.; Adams, R. W.; Morris, G. A.; Clayden, J. Angew. Chem., Int. Ed. 2014, 53, 151. (2) (a) Yanagiya, M.; Matsuda, F.; Hasegawa, K.; Matsumoto, T. Tetrahedron Lett. 1982, 23, 4039. (b) Evans, D. A.; Coleman, P. J.; Côté, B. J. Org. Chem. 1997, 62, 788. (c) Takemoto, Y.; Ishii, K.; Honda, A.; Okamoto, K.; Yanada, R.; Ibuka, T. Chem. Commun. 2000, 1445−1446. (d) Evans, D. A.; Connell, B. T. J. Am. Chem. Soc. 2003, 125, 10899. (e) Efremov, I.; Paquette, L. A. J. Am. Chem. Soc. 2000, 122, 9324. (f) Kodama, S.; Hamashima, Y.; Nishide, K.; Node, M. Angew. Chem., Int. Ed. 2004, 43, 2659. (g) Dias, L. C.; Vieira, A. S.; Barreiro, E. J. Org. Biomol. Chem. 2016, 14, 2291. (3) (a) Shirokawa, S.; Kamiyama, M.; Nakamura, T.; Okada, M.; Nakazaki, A.; Hosokawa, S.; Kobayashi, S. J. Am. Chem. Soc. 2004, 126, 13604. (b) Hosokawa, S.; Tatsuta, K. Mini-Rev. Org. Chem. 2008, 5, 1. (c) Hosokawa, S. Yuki Gosei Kagaku Kyokaishi 2009, 67, 24. (4) (a) Nakamura, T.; Shirokawa, S.; Hosokawa, S.; Nakazaki, A.; Kobayashi, S. Org. Lett. 2006, 8, 677. (b) Jiang, X.; Liu, B.; Lebreton, S.; De Brabander, J. K. J. Am. Chem. Soc. 2007, 129, 6386. (c) Nicolaou, K. C.; Guduru, R.; Sun, Y.-P.; Banerji, B.; Chen, D. Y.-K. Angew. Chem., Int. Ed. 2007, 46, 5896. (d) Nicolaou, K. C.; Sun, Y.-P.; Guduru, R.; Banerji, B.; Chen, D. Y.-K. J. Am. Chem. Soc. 2008, 130, 3633. (e) Schmauder, A.; Müller, S.; Maier, M. E. Tetrahedron 2008, 64, 6263. (f) Lipshutz, B.; Amorelli, B. J. Am. Chem. Soc. 2009, 131, 1396. (g) Yamaoka, M.; Fukatsu, Y.; Nakazaki, A.; Kobayashi, S. Tetrahedron Lett. 2009, 50, 3849. (h) Schmauder, A.; Sibley, L.; Maier, M. E. Chem. - Eur. J. 2010, 16, 4328. (i) Paterson, I.; Kan, S. B. J.; Gibson, J. Org. Lett. 2010, 12, 3724. (j) Hosokawa, S.; Matsushita, K.; Tokimatsu, S.; Toriumi, T.; Suzuki, Y.; Tatsuta, K. Tetrahedron Lett. 2010, 51, 5532. (k) Matsui, R.; Seto, K.; Sato, Y.; Suzuki, T.; Nakazaki, A.; Kobayashi, S. Angew. Chem., Int. Ed. 2011, 50, 680. (l) Fujita, K.; Matsui, R.; Suzuki, T.; Kobayashi, S. Angew. Chem., Int. Ed. 2012, 51, 7271. (m) Höfle, G.; Gerth, H.; Reichenbach, H.; Kunze, B.; Sasse, F.; Forche, E.; Prusov, E. Chem. - Eur. J. 2012, 18, 11362. (n) Hartmann, O.; Kalesse, M. Angew. Chem., Int. Ed. 2014, 53, 7335. (o) MiyatakeOndozabal, H.; Kaufmann, E.; Gademann, K. Angew. Chem., Int. Ed. 2015, 54, 1933. (p) Rao, K. N.; Kanakaraju, M.; Kunwar, A. C.; Ghosh, S. Org. Lett. 2016, 18, 4092. (q) Liao, L.; Zhou, J.; Xu, Z.; Ye, T. Angew. Chem., Int. Ed. 2016, 55, 13263. (r) Villadsen, N. L.; Jacobsen, K. M.; Keiding, U. B.; Weibel, E. T.; Christiansen, B.; Vosegaard, T.; Bjerring, M.; Jensen, F.; Johannsen, M.; Tørring, T.; Poulsen, T. B. Nat. Chem. 2017, 9, 264. (5) (a) Mukaeda, Y.; Kato, T.; Hosokawa, S. Org. Lett. 2012, 14, 5298. (b) Tsukada, H.; Mukaeda, Y.; Hosokawa, S. Org. Lett. 2013, 15, 678. 2397

DOI: 10.1021/acs.orglett.7b00920 Org. Lett. 2017, 19, 2394−2397