Phosphine-Catalyzed Asymmetric (3+2) Annulations of δ-Acetoxy

Letter pubs.acs.org/OrgLett

Phosphine-Catalyzed Asymmetric (3+2) Annulations of δ‑Acetoxy Allenoates with 2‑Naphthols Dong Wang and Xiaofeng Tong* Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, 1 Gehu Road, Changzhou, 213164, China S Supporting Information *

ABSTRACT: Phosphine-catalyzed (3+2) annulations of δacetoxy allenoates with 2-naphthols are reported, wherein the δC of allentoate reacts with the αC of 2-naphthol to form the C−C bond while a C−O bond is formed between the γC of allenoate and the hydroxyl group of 2-naphthol. When (R)SITCP is used as the catalyst, 1,2-dihydronaphtho[2,1-b]furans are obtained in moderate to good yields and with high enantioselectivity. This method is useful for the construction of enantiomerically enriched atropoisomeric furans via a central to axial chirality conversion strategy. Scheme 1. Phosphine-Catalyzed Annulations of δ-Acetoxy Allenoate 1 with Various Bis-nucleophiles

T

he 1,2-dihydronaphtho[2,1-b]furans (DHN) are an important class of heterocycles due to their diverse biological activities, including antiinflammatory activity, 5lypoxygenase inhibitor, melatonin receptor ligand, and so on.1 While numerous methods have been developed toward their synthesis,2 the asymmetric preparation in a catalytic fashion is still less explored. Therefore, the development of new catalytic methodologies for DHN synthesis with high enantiomerical enrichment remains an area of current interest. In the last decades, organocatalysis has emerged as an important tool in organic synthesis.3 As is the case, several asymmetric organocatalytic approaches for DHN synthesis have recently appeared.4 For example, Jørgensen et al. have presented the synthesis of DHN hemiacetal derivatives with good enantioselectivity using aminocatalysis in a one-pot process.4a A Friedel−Crafts/substitution domino reaction between bromonitroalkene and 2-naphthol under squaramide catalysis has also been developed by the group of Aleman, which affords DHN with excellent enantioselectivity.4b More recently, Gasperi and co-workers have reported a similar domino sequence but with low enantioselectivity.4c These contributions strongly rely on the 1C,3O-bisnucleophilic reactivity of 2-naphthol with the combination of various 1C,2C-biselectrophilic components to furnish (3+2) annulations. However, likely due to the lack of either suitable 1C,2Cbiselectrophiles or asymmetric catalysis systems, this 2naphthol-based (3+2) annulation strategy for straightforward enantioselective synthesis of DHN is severely restricted.5 With these considerations in mind, we envisioned that δacetoxy allenoate 1 would be an appropriate bis-electrophiliccomponent for annulation with 2-naphthol under Lewis base catalysis (Scheme 1).6 In the presence of phosphine catalyst, allenoate 1 can be readily converted into 3phosphonium-2,4-dienoate A via 1,4-addition of phosphine and subsequent 1,2-elimination of acetate group. Cationic intermediate A has been proven to exhibit good bis-electro© 2017 American Chemical Society

philic reactivity,6 which complements the well-known zwitterionic intermediates in the field of phosphine catalysis.7 The αC,γC-biselectrophilic reactivity of A was clearly demonstrated by the (3+3) annulation with 1,3-dicarbonyl compound (Scheme 1a).6a Interestingly, its δC,γC-biselectrophilic reactivity could also be revealed when β-carbonyl amides were used as the other annulation partner (Scheme 1b).6b,c These reports illustrate that the annulation mode of intermediate A can be subtly tuned, although the key control elements are yet not clear.8 Nevertheless, an annulation between 2-naphthol and Received: October 18, 2017 Published: November 20, 2017 6392

DOI: 10.1021/acs.orglett.7b03250 Org. Lett. 2017, 19, 6392−6395

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Organic Letters allenoate 1 would be anticipated to take place on the basis of their unique chemical behaviors under phosphine catalysis. In view of a similar reactivity feature of 2-naphthol as 1,3dicarbonyl compound, we initially deduced that the reaction of allenoate 1a and 2-naphthol 2a would follow the (3+3) annulation pathway. However, when this reaction was conducted in toluene at 25 °C with the assistance of PPh3 (10 mol %) and K2CO3 (1.3 equiv), the anticipated (3+3) annulation product 3aa was not detected while the (3+2) annulation product 4aa was isolated in 67% yield (Table 1,

Scheme 2. Reaction Scope of Allenoates 1

Table 1. Catalyst Screening

a

entry 1). The yield of 4aa was improved to as high as 95% when PPhMe2 was used as the catalyst (Table 1, entry 2). These results encouraged us to develop the asymmetric version with the use of (R)-SITCP9 as the chiral catalyst. To our delight, under the otherwise identical conditions, the use of (R)-SITCP resulted in the isolation of 4aa in 95% yield and 88% ee (Table 1, entry 3). Reducing the reaction temperature to 0 °C was found to be beneficial for the enantioselectivity (92%) without any erosion of the reaction efficiency (Table 1, entry 4). The absolute configuration of 4aa was established on the base of X-ray analysis of its alcohol derivative 11 (Scheme 6 and Figure 1, left).

(S)-SITCP was used as catalyst.

4ka, resulted from the reactions of allenoates 1i−1k bearing a 2-halo-substituted phenyl group, sharply dropped to ca. 40% yield, indicating the strong electronic and steric effect. On the other hand, the reactions of allenoates with an electron-rich phenylgroup were extremely efficient, even for the cases of 1l and 1m with 2-Me-C6H4 and 2-MeO-C6H4 substituents, respectively. Allenoates 1n and 1o with a heteroaryl group were also suitable substrates, delivering 4na and 4oa with good enantioselectivity albeit in somewhat lower yields. While the reaction efficiency of allenoates 1p−1r bearing an alkyl substituent was found to be relatively lower, high enantioselectivity was still obtained. Notably, the reaction of allenoate 1s derived from (S)-8,9-dihydroperillaldehyde with 2a exhibited excellent diastereoslectivity, affording product 4sa as one single isomer. The reaction of allenoate 1t derived from (R)citronellal also gave product 4ta with >20:1 dr. Gratefully, ent-4ta could be readily obtained with the same level of diastereoselectivity when (S)-SITCP was instead used as catalyst. Interestingly, when allenoate 1u with a 2-propenyl group at δC position was subjected to the standard conditions, product 4ua was isolated in 43% yield and 91% ee along with a unexpected product 5 in 20% yield (Scheme 3). Apparently, product 5 was resulted from the attack of 2a at the C6-position of 3-phosphonium-2,4,6-trienoate intermediate A′. Likely because of the C5 position remote from the chiral environment of phosphine catalyst, racemic product 5 was obtained. Next, we moved on to explore the substrate scope of 2naphthols 2 by using the reaction with allenoate 1a (Scheme 4). 2-Naphthols with electron-donating groups, such as 7OTBS and 7-OiPr, as well as 6-OTBS, were proven to be highly reactive, affording the corresponding products in excellent yields. The reaction of 7-bromonaphthalen-2-ol 2d with 1a produced product 4ad only in 50% yield. The relative lower yield would arise from the reduced C2-nucleophilicity imposed

Figure 1. X-ray structures of compounds 11 (left) and 12a (right).

With the optimized conditions in hand, we then turned our attention to investigating the scope of (3+2) annulations of allenoates 1 with 2-naphthol 2a. As shown in Scheme 2, various phenyl substituents at the δC position of allenoates 1 [4-F− C6H4, 4-Cl−C6H4, 4-Br−C6H4, 4-iPr−C6H4, 4-MeO−C6H4, 3Br−C6H4, 3-MeO−C6H4, 2-Cl−C6H4, 2-Br−C6H4, 2-I−C6H4, 2-Me−C6H4, 2-MeO−C6H4] were tolerated and products 4aa−4ma were isolated with good to excellent enantioselectivity (85%−93% ee). However, the reaction yields were found to be strongly dependent on the electronic property of substituents on the phenyl group. For instance, allenoates 1 bearing an electron-poor phenyl group, such as 1b−1d and 1g, were relatively less active, affording the corresponding products in 69%−85% yields. Moreover, the yields of compounds 4ia− 6393

DOI: 10.1021/acs.orglett.7b03250 Org. Lett. 2017, 19, 6392−6395

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while the enantioselectivity still remained in an excellent level (eq 1). We were delighted to find that this (3+2) annulation was also applicable to 1-naphthol 8 (eq 2). Under the standard conditions, the reaction of allenoate 1a and 1-naphthol 8 smoothly occurred to deliver (3+2) annulation product 9 in 43% yield and 92% ee. To our surprise, (3+3) annulation product 10 was also isolated albeit only in 32% yield and 27% ee. This result was contrast to the fact that no (3+3) annulation products were detected in all of cases of 2-naphthols 2a−2g. The observation of (3+3) annulation product 10 provided a constructive clue to the reaction mechanism. Compared with 1-naphthol 8, the reactive αC-site of 2naphthol 2a is believed to be more steric hindrance due to the A1,3-interaction. For 3-phosphonium-2,4-dienoate A, the αCposition has more steric hindrance than the δC-position. Therefore, to minimize the steric repulsion, 2-naphthol 2a would preferentially attack intermediate A at its δC-position via a Friedel−Crafts type process to afford intermediate B, which underwent oxa-Michael addition via a half-chair conformation, thus finally leading to product trans-4aa (Scheme 5). On the

Scheme 3. Reaction of Allenaote 1u and 2a

Scheme 4. Substrate Scope of 2-Naphthols 2

Scheme 5. Rational for Different Reactivity between 2Naphthol and 1-Naphthol

by bromo-substitution. Moreover, the reaction was also strongly affected by steric hindrance. Indeed, 8-substituted 2naphthols 2f and 2g showed very low activity, giving products 4af and 4ag only in ca. 30% yield.

other hand, due to less steric hindrance of the βC-site of 1naphthol 8, it would have a second chance to attack the congested αC-position of intermediate A (Scheme 5, path b) along with the major δC-position attack (Scheme 5, path a). As a result, intermediate C would be formed, which was responsible for the (3+3) annulation product 10. We thus concluded that the annulation mode of 3-phosphonium-2,4dienoate A would be mainly dependent on the steric hindrance of the upcoming bis-nucleophiles. To showcase the synthetic utility of this method, the reaction of 1a and 2a was conducted in a 1 mmol scale. Although a prolonged reaction time was required, product 4aa was still isolated in 92% yield and 92% ee even in the presence of 5 mol % of (R)-SITCP (Scheme 6). Upon the treatment of DIBALH, 4aa could be converted into alcohol 11 in 98% yield and 91% ee. We also attempted to covert enantioenriched dihydrofuran 4ka into furan atropisomer inspired by the recent report from the group of Bonne and Rodriguez.11 This oxidative central-toaxial chirality conversion strategy was finally realized by using DDQ as the oxidant, affording axially chiral furan 12a in 47% yield and 90% ee. Its absolute configuration was unambiguously identified to be aS by X-ray diffraction (Figure 1, right). However, the enantioselectivity for the case of 4la with a smaller 2-Me-C6H4 substituent unfortunately dropped to 70% (Scheme 6).

In considering other possible C,O-bisnucleophile partners for the (3+2) annulations with allenaotes 1, we elected to pursue the use of phenol, which would result in the biologically interesting 2,3-dihydrobenzofuran.10 After several attempts, it was found that only 3,5-dimethoxyphenol 6 exhibited moderate reactivity toward (3+2) annulations with allenoates 1a and 1p 6394

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Yodis, L. A.; Chabot Fletcher, M.; Tzimas, M.; Webb, E. F.; Breton, J. J.; Griswold, D. E. J. Med. Chem. 1996, 39, 5035. (c) Matsunaga, N.; Kaku, T.; Ojida, A.; Tanaka, T.; Hara, T.; Yamaoka, M.; Kusaka, M.; Tasaka, A. Bioorg. Med. Chem. 2004, 12, 4313. (2) For selected examples, see: (a) Kshirsagar, U. A.; Regev, C.; Parnes, R.; Pappo, D. Org. Lett. 2013, 15, 3174. (b) Vaughan, D.; Jha, A. Tetrahedron Lett. 2009, 50, 5709. (c) Wang, F.; Yang, G.; Zhang, Y. J.; Zhang, W. Tetrahedron 2008, 64, 9413. (d) Reich, N. W.; Yang, C.G.; Shi, Z.; He, C. Synlett 2006, 2006, 1278. (e) Pancote, C. G.; Carvalho, B. S.; Luchez, C. V.; Fernandes, J. P. S.; Politi, M. J.; Brandt, C. A. Synthesis 2009, 2009, 3963. (f) Yadav, A. K.; Singh, B. K.; Singh, N.; Tripathi, R. P. Tetrahedron Lett. 2007, 48, 6628. (g) Haselgrove, T. D.; Jevric, M.; Taylor, D. K.; Tiekink, E. R. T. Tetrahedron 1999, 55, 14739. (h) He, Z.; Yudin, A. K. Org. Lett. 2006, 8, 5829. (3) (a) Asymmetric Organocatalysis; Berkessel, A.; Groger, H., Eds.; Wiley-VCH: Weinheim, 2005. (b) Enantioselective Organocatalysis; Dalko, P. I. Ed.; Wiley-VCH: Weinheim, 2007. (4) (a) Albrecht, L.; Ransborg, L. K.; Lauridsen, V.; Overgaard, M.; Zweifel, T.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2011, 50, 12496. (b) Jarava-Barrera, C.; Esteban, F.; Navarro-Ranninger, C.; Parra, A.; Aleman, J. Chem. Commun. 2013, 49, 2001. (c) Vetica, F.; Figueiredo, R. M.; Cupioli, E.; Gambacorta, A.; Loreto, M. A.; Miceli, M.; Gasperi, T. Tetrahedron Lett. 2016, 57, 750. (d) Lu, A.; Hu, K.; Wang, Y.; Song, H.; Zhou, Z.; Fang, J.; Tang, C. J. Org. Chem. 2012, 77, 6208. (5) Shao, L.; Wang, Y.-H.; Zhang, D.-Y.; Xu, J.; Hu, X.-P. Angew. Chem., Int. Ed. 2016, 55, 5014. (6) (a) Hu, J.; Dong, W.; Wu, X.-Y.; Tong, X. Org. Lett. 2012, 14, 5530. (b) Xing, J.; Lei, Y.; Gao, Y.-N.; Shi, M. Org. Lett. 2017, 19, 2382. (c) Ni, C.; Chen, J.; Zhang, Y.; Hou, Y.; Wang, D.; Tong, X.; Zhu, S.-F.; Zhou, Q.-L. Org. Lett. 2017, 19, 3668. (d) Zhou, W.; Ni, C.; Chen, J.; Wang, D.; Tong, X. Org. Lett. 2017, 19, 1890. (e) Ni, C.; Zhou, W.; Tong, X. Tetrahedron 2017, 73, 3347. (7) For selected reviews, see: (a) Wang, Z.; Xu, X.; Kwon, O. Chem. Soc. Rev. 2014, 43, 2927. (b) Fan, Y. C.; Kwon, O. Chem. Commun. 2013, 49, 11588. (c) Xie, P.; Huang, Y. Eur. J. Org. Chem. 2013, 2013, 6213. (d) Gomez, C.; Betzer, J.-F.; Voituriez, A.; Marinetti, A. ChemCatChem 2013, 5, 1055. (e) Cowen, B. J.; Miller, S. J. Chem. Soc. Rev. 2009, 38, 3102. (f) Nair, V.; Menon, R. S.; Sreekanth, A. R.; Abhilash, N.; Biju, A. T. Acc. Chem. Res. 2006, 39, 520. (g) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535. (h) Xiao, Y.; Sun, Z.; Guo, H.; Kwon, O. Beilstein J. Org. Chem. 2014, 10, 2089. (i) Wang, T.; Han, X.; Zhong, F.; Yao, W.; Lu, Y. Acc. Chem. Res. 2016, 49, 1369. (8) (a) Zhang, Y.; Tong, X. Org. Lett. 2017, 19, 5462. (b) Gu, Y.; Li, F.; Hu, P.; Liao, D.; Tong, X. Org. Lett. 2015, 17, 1106. (9) Zhu, S.-F.; Yang, Y.; Wang, L.-X.; Liu, B.; Zhou, Q.-L. Org. Lett. 2005, 7, 2333. (10) Roupe, K. A.; Remsberg, C. M.; Yanez, J. A.; Davies, N. M. Curr. Clin. Pharmacol. 2006, 1, 81. (11) Raut, V. S.; Jean, M.; Vanthuyne, N.; Roussel, C.; Constantieux, T.; Bressy, C.; Bugaut, X.; Bonne, D.; Rodriguez, J. J. Am. Chem. Soc. 2017, 139, 2140 In the abovementioned report, either PhI(OAc)2 or MnO2 is an efficient oxidant. However, they are found to be invalid for the transformation of 4ka into 12a..

Scheme 6. Synthetic Transformations

In summary, we have developed the phosphine-catalyzed asymmetric (3+2) annulations of δ-acetoxy allenoates 1 and 2naphthols 2, which provide a facile method for DHN synthesis with good reaction efficiency and enantioselectivity under mild reaction conditions. This method is also applicable to both 3,5dimethoxyphenol and 1-naphthol. Furthermore, the observation of side (3+3) annulation product 10 revealed that the steric interaction between cationic intermediate A and the nucleophiles would be a key control element for the regioselectivity of allenoate 1.

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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.7b03250. Experimental details, data, and spectra (PDF) Accession Codes

CCDC 1580593−1580594 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

Xiaofeng Tong: 0000-0002-6789-1691 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work is supported by NSFC (No. 21472042 and 21772016), the Jiangsu Province Funds for Distinguished Young Scientists (BK20160005), and Qing-Lan Project. We are also grateful to Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, Changzhou University for financial support.

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REFERENCES

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DOI: 10.1021/acs.orglett.7b03250 Org. Lett. 2017, 19, 6392−6395