Silver-Catalyzed Cyclopropanation of Alkenes Using N

Letter Cite This: Org. Lett. 2017, 19, 6646−6649

pubs.acs.org/OrgLett

Silver-Catalyzed Cyclopropanation of Alkenes Using N‑Nosylhydrazones as Diazo Surrogates Zhaohong Liu,† Xinyu Zhang,† Giuseppe Zanoni,§ and Xihe Bi*,†,‡ †

Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, Department of Chemistry, Northeast Normal University, Changchun 130024, China ‡ State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China § Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy S Supporting Information *

ABSTRACT: An efficient silver-catalyzed [2 + 1] cyclopropanation of sterically hindered internal alkenes with diazo compounds in which roomtemperature-decomposable N-nosylhydrazones are used as diazo surrogates is reported. The unexpected unique catalytic activity of silver was ascribed to its dual role as a Lewis acid activating alkene substrates and as a transition metal forming silver carbenoids. A wide range of internal alkenes, including challenging diarylethenes, were suitable for this protocol, thereby affording a variety of cyclopropanes with high efficiency in a stereoselective manner under mild conditions.

T

intrinsic explosive property of diazo compounds prevent their use for large-scale manufacturing. Recent advances in the activation of aryldiazoacetates by silver catalysis resulted in preparatively useful yields while requiring a large stoichiometric excess for internal olefins as substrates (5−10 equiv).7d Other non-diazo starting materials, such as benzylidene iron carbene complex (path b)8 and toxic α-[(alkoxycarbonyl)oxy]stannanes (path c),9 were also explored for the cyclopropanation reaction, but they required stoichiometric amounts of preformed metal carbenes. Echavarren and co-workers employed cycloheptatrienes as a safe alternative to diazo compounds to generate gold(I) carbenoids via a retro-Buchner reaction under catalytic conditions, affording a range of 1,2,3-trisubstituted cyclopropanes in moderate to excellent yields (path d).10 In addition, zinc vinyl carbenoids generated from cyclopropenes with diarylethenes afforded vinylcyclopropanes in medium yields (path e).11 Nevertheless, the development of novel and efficient methods enabling the cyclopropanation of sterically hindered internal alkenes is constantly in demand. As part of our continued interest in the low-temperature decomposition of N-nosylhydrazones and their synthetic applications with silver catalysis,12 we herein report an efficient silver-catalyzed cyclopropanation of 1,2-diarylalkenes with N-nosylhydrazones (path f). As further disclosed herein, this protocol could be extended to other internal and terminal alkenes. Initially, optimization of the reaction conditions was performed using the reaction of benzaldehyde N-nosylhydrazone (1a) with (E)-1,2-diphenylethene (2a) as a model reaction. Selected results on the effect of transition metal salts as catalysts are summarized in Scheme 1. Unexpectedly, commonly used carbene transfer catalysts, such as rhodium,

he cyclopropane moiety, itself a synthon in organic synthesis,1 can be found in bioactive natural products and pharmaceuticals.2 Consequently, the construction of the cyclopropane ring, especially with easily available starting materials, has attracted considerable attention.3 In this context, the [2 + 1] cyclopropanation of alkenes plays a dominating role.3,4 However, this method remains problematic because most alkene substrates are restricted to terminal, activated, or aliphatic internal olefins.5 The application to unactivated 1,2disubstituted alkenes, especially the more sterically hindered diarylethenes, is still a challenging task.6 To date, very few synthetically useful methods for the cyclopropanation of diarylalkenes have been described (Figure 1). For instance, metal carbenoids generated by the decomposition of diazo compounds such as diazo esters can be cyclized with diarylalkenes to form cyclopropanes; unfortunately, disappointing yields (below 50%) are often observed (path a).7 Moreover, the inherent toxicity and

Figure 1. Strategies for the [2 + 1] cyclopropanation of 1,2diarylalkenes. © 2017 American Chemical Society

Received: October 30, 2017 Published: November 29, 2017 6646

DOI: 10.1021/acs.orglett.7b03374 Org. Lett. 2017, 19, 6646−6649

Letter

Organic Letters Scheme 1. Screening of Transition Metal Catalystsa,b

Scheme 2. Scope of N-Nosylhydrazones and 1,2Diarylalkenesa

a

Reaction conditions: 1a (0.3 mmol), NaH (0.45 mmol), and DCM (6 mL) were stirred at rt for 1 h, and then the catalyst and 2a (0.45 mmol) were added, after which the mixture was stirred at 40 °C for 18 h. bYields were calculated from 1H NMR spectroscopy with CH2Br2 as the internal standard. cIsolated yield in parentheses.

palladium, copper, gold, zinc, and iron salts, did not promote the desired cyclopropanation reaction.13 In contrast, all of the tested silver salts proved to be suitable for the reaction, affording 1,2,3-triphenylcyclopropane (3a) in good to excellent yields (as estimated by 1H NMR analysis of the crude mixtures). Notably, the cyclopropanation of alkenes with aryl diazomethanes has been achieved both by photolysis14a and with transition metal catalysts, such as dirhodium,14b copper,14c ruthenium,14d osmium,14e zinc,14f,g and iron salts,14h but none of them proved to be suitable for 1,2-diarylalkenes. Given these observations, the success of the [2 + 1] cycloaddition of sterically hindered 1,2-diarylalkenes with N-nosylhydrazones was far from certain. Although the exact reason for the unique catalytic activity of silver for aryl diazomethanes remains unclear, this may be due to the dual role of the silver salt as a Lewis acid to activate alkene substrates and as a transition metal to form silver carbenoids with the in situ-released aryl diazomethanes.15 With the optimal reaction conditions in hand, we set out to explore the scope and generality of the reaction with various substituted N-nosylhydrazones and 1,2-diarylalkenes. As depicted in Scheme 2, the cyclopropanation of trans-stilbene (2a) proceeded effectively with a wide range of Nnosylhydrazones derived from aldehydes. Both electrondonating (3b, 3c) and electron-withdrawing (3d, 3e) substituents on the phenyl moiety were well-tolerated at either the para (3c, 3d, 3e) or meta position (3b). N-Nosylhydrazones with an ortho-substituted aryl ring gave the related products (3f, 3g) in slightly reduced yields, possibly because of steric hindrance. Remarkably, phenyl-disubstituted N-nosylhydrazones also provided the desired cyclopropanated products (3h, 3i) in good yields. Fused aromatic 2-naphthyl-Nnosylhydrazone also served as a substrate for this cyclopropanation, providing the desired product 3j in 64% yield. A range of medicinally relevant heterocycles, such as quinolone-, indole-, thiophene-, and furan-based N-nosylhydrazones, also reacted efficiently, providing the corresponding products (3k, 3l, 3m, and 3n) in 52−78% yield. In addition to Nnosylhydrazones generated from (hetero)aryl aldehydes, those derived from selected α,β-unsaturated aldehydes could actively participate in the reaction with trans-stilbene, affording valuable alkynyl and vinyl cyclopropanes in synthetically useful yields (3o and 3p, 43% and 80%, respectively). However, the product arising from an aliphatic N-nosylhydrazone (3q) could not be isolated because of the competing Bamford−Stevens reaction

a

Reaction conditions: 1 (0.3 mmol), NaH (0.45 mmol), and DCM (6.0 mL) were stirred at rt for 1 h, and then 2 (0.45 mmol) and AgOTf (0.06 mmol) were added, after which the mixture was stirred at 40 °C for 18 h. Isolated yields are shown. bGram-scale synthesis.

that leads to a terminal olefin and olefinic dimers.3a,5b To establish practical laboratory-scale utility, the reaction of Nnosylhydrazone 1e and trans-stilbene was performed on a 5 mmol scale, providing the corresponding product 3e in only a slightly decreased yield (1.4 g, 90%). Subsequently, the scope of 1,2-diarylalkenes for this cyclopropanation reaction was investigated by treating differently substituted alkenes with 3methoxyphenyl-N-nosylhydrazone (1b). As summarized in Scheme 2, trans-1,2-diaryl olefins bearing methyl, trifluoromethyl, and chloride substituents afforded the corresponding products (3r−v) in good to excellent yields (66−93%). A further increase in the steric hindrance of alkenes was also possible; for instance, (E)-1-methyl-1,2-diphenylethene efficiently reacted with 1b to give the desired product 3w in 76% yield with a dr value of 1.5:1. Unfortunately, N-nosylhydrazone 1r derived from acetophenone was unreactive with sterically hindered alkene 2b, but terminal alkene 2h efficiently reacted with N-nosylhydrazone 1r to give the product 3y in 75% yield with excellent diastereoselectivity (trans:cis = 20:1).16

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DOI: 10.1021/acs.orglett.7b03374 Org. Lett. 2017, 19, 6646−6649

Letter

Organic Letters Further assessment of the substrate scope for this protocol was performed by treating N-nosylhydrazone 1b with various substituted alkenes 4, including chalcones and mono-, di-, tri-, and fully substituted olefins. As shown in Scheme 3, all of the Scheme 3. Variation of Alkenesa Scheme 4. Intramolecular Cyclopropanation

affording the corresponding cyclopropanes 7a−d in good to excellent yields (78−95%). The exclusively exo configuration was confirmed by the X-ray crystal structure of 7c. In summary, we have developed a highly effective and practical one-pot method for the [2 + 1] cyclopropanation of sterically hindered internal olefins, especially for the challenging 1,2-diarylethenes. A unique catalytic activity of selected silver salts was observed for this transformation, which was ascribed to their dual function as Lewis acids and transition metals. The method described here features several advantages, such as easy accessibility of the starting materials, simple operation, high steroselectivity, broad substrate scope, high reaction efficiency, and high product yields. Overall, this work represents an extremely simple method for the [2 + 1] cyclopropanation of alkenes, including both internal and terminal alkenes, in both intramolecular and intermolecular reaction patterns.

a Reaction conditions: 1b (0.3 mmol), NaH (0.45 mmol), and DCM (6.0 mL) were stirred at rt for 1 h, and then 4 (0.45 mmol) and AgOTf (0.06 mmol) were added, after which the mixture was stirred at 40 °C for 18 h. The trans/cis diastereoisomeric ratios shown in parentheses were determined by 1H NMR spectroscopy.

screened alkenes proved reactive, delivering the target products (5a−i) in satisfactory yields (40−98%). In the case of trisubstituted and tetrasubstituted alkenes, the desired products (5c and 5d) were formed in excellent yields. Notably, cyclic and bicyclic olefins are also suitable substrates, affording the corresponding bridged cyclic cyclopropanes (5e−g) in high yields. In particular, extension of the method to an alkylsubstituted terminal olefin gave the product in high yield with moderate selectivity (5h). It is worth mentioning that both cyclohexene (4f) and 1-octene (4h) were poor cyclopropanation substrates with rhodium5b and iron catalysts.17 In contrast, the cyclopropanation of osthole, a representative naturally occurring internal alkene, with 1b chemoselectively led to product 5i in 85% yield, wherein only the terminal moiety underwent cyclopropanation. With regard to the effect of the alkene geometry on the reaction outcome, we wondered how the structure of the reactant alkene would control the stereochemistry in the product of cyclopropanation. Under the optimized catalytic conditions, (Z)-4-octene (4j) afforded the cis-cyclopropane product in 86% yield as a 2.5:1 isomeric mixture (5j). Conversely, with (E)-4-octene (4k), the exclusive formation of corresponding trans-cyclopropane (5k) was observed in excellent yield (89%). These experimental results showed that silver-catalyzed cyclopropanation took place with complete stereospecificity and suggested that the cycloaddition of silver carbenes to alkenes may proceed in a concerted manner.18 Finally, we expanded our approach to intramolecular cyclopropanation of N-nosylhydrazones with a tethered olefin moiety at the ortho position (6a−d) in order to synthesize highly strained bicyclic systems (Scheme 4).19 AgOTFA was superior to AgOTf as a catalyst for this transformation,

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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.7b03374. Experimental procedures and copies of spectra (PDF) Accession Codes

CCDC 1522924 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 e-mailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K.; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Home page: www.bigroup.top/. ORCID

Zhaohong Liu: 0000-0001-9951-8675 Xihe Bi: 0000-0002-6694-6742 6648

DOI: 10.1021/acs.orglett.7b03374 Org. Lett. 2017, 19, 6646−6649

Letter

Organic Letters Notes

Chem. Soc. Rev. 2015, 44, 8124. (d) Fang, G.; Cong, X.; Zanoni, G.; Liu, Q.; Bi, X. Adv. Synth. Catal. 2017, 359, 1422. (16) When N-tosylhydrazone was used as the diazo source, 3y was obtained with poor diastereoselectivity (dr = 2:1). See: Barluenga, J.; Quiñones, N.; Tomás-Gamasa, M.; Cabal, M.-P. Eur. J. Org. Chem. 2012, 2012, 2312. (17) Doyle, M. P.; Griffin, J. H.; Bagheri, V.; Dorow, R. L. Organometallics 1984, 3, 53. (18) (a) Wulfman, D. S.; McDaniel, R. S.; Peace, B. W. Tetrahedron 1976, 32, 1241. (b) Hansen, J.; Autschbach, J.; Davies, H. M. L. J. Org. Chem. 2009, 74, 6555. (19) (a) Taber, D. F.; Guo, P.; Guo, N. W. J. Am. Chem. Soc. 2010, 132, 11179. (b) Taber, D. F.; Guo, P. J. Org. Chem. 2008, 73, 9479.

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the NNSFC (21522202, 21502017).

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REFERENCES

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DOI: 10.1021/acs.orglett.7b03374 Org. Lett. 2017, 19, 6646−6649