Ag(I)-Catalyzed Tandem Reaction of Conjugated Ene-yne-ketones in

Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

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Ag(I)-Catalyzed Tandem Reaction of Conjugated Ene-yne-ketones in the Presence of PhI(OAc)2 and Triethylamine: Synthesis of 2‑Alkenylfurans Shanjian Mao, Ling Tang, Chenggui Wu, Xianxia Tu, Qianwen Gao, and Guisheng Deng* Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China) and Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, Hunan Normal University, Changsha 410081, China

Org. Lett. Downloaded from pubs.acs.org by IOWA STATE UNIV on 03/26/19. For personal use only.

S Supporting Information *

ABSTRACT: Silver-catalyzed tandem cyclization−elimination reactions of conjugated ene-yne-ketones in PhI(OAc)2/ triethylamine system lead to the formation of 2-alkenylfurans. 2-Furylsilver carbene and phenyliodonium ylide are proposed as the key intermediates in these transformations.

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Scheme 1. Protocols for the Synthesis of 2-Alkenylfuranones

uran derivatives are important frameworks of many biologically active molecules and drug intermediates.1 Furans also serve as valuable building blocks for organic synthesis.2 In addition to traditional methods, many novel methods for synthesis of various substituted furans have been developed.3 In particular, transition-metal-catalyzed cascade reactions of conjugated ene-yne-ketones have provided useful approaches for the synthesis of furan derivatives. Among them, Pd(II),4 Cu(I),5,6b Cu(II),6 zinc,7 Au(III or I),8 Rh(II or I),9 and Cr(0), W(0), Ru(II), Rh(I), Pt(II)10 species-intermediated syntheses of furan derivatives have attracted great attention. These cascade reactions proceed via 5-exo-dig cyclization involving a nucleophilic attack of carbonyl oxygen at a transition-metal-activated triple bond, which can also be represented as a Zwitterionic intermediate, to produce a relatively stable (2-furyl)carbene−metal complex.11 The complex can subsequently participate in various transformations,12 such as 2-olefination, affording 2-vinylfuran derivatives. Some achievements in the field of 2-olefination have been made based on this strategy. For example, Cao et al. reported a regioselective synthesis of 2-vinylfurans by 1,2-H shift of palladium-carbene (Scheme 1a).4d Wang et al. reported that oxidation of 2-furylpalladium carbene intermediate by using benzoquinone as oxidant afforded 2-alkenylfuran (Scheme 1b).4a,e The coupling reaction of (2-furyl)copper carbene with ethyl diazoacetate also afforded 2-alkenylfuran in good yield.5d Barluenga et al. revealed that (2-furyl)copper carbene yielded the furyl dimer without 1,2-H shift product.5g Recently, López and Vicente reported ZnCl2-catalyzed cross-coupling reactions of enynones with diazoacetates/vinyl diazoacetates to generate 2-alkenylfurans containing trisubstituted olefin moieties in moderate to good stereoselectivities.7f,g Sun et al. disclosed stereoselective synthesis of tetrasubstituted furylalkenes via © XXXX American Chemical Society

XantPhos(AuCl)2/AgSbF6-catalyzed cross-coupling of enynones with diazo compounds (Scheme 1c).13 Received: February 25, 2019

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DOI: 10.1021/acs.orglett.9b00712 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters Table 1. Optimization of Cyclization−Olefination Conditionsa

entry

catalyst (mol %)

PhI(OAc)2

base (equiv)

solvent

T (°C)

t (h)

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

AgOAc (20) AgOAc (20) none none AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20) AgOCOCF3 (20) AgSbF6 (20) AgBF4 (20) AgOAc (5) AgOAc (10) AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20) AgOAc (20)

0 0 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 1 3 2 2 2

none TEA (1.5) none TEA (1.5) none TEA (1.5) DIPEA (1.5) DBU (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (1.5) TEA (0.1) TEA (1) TEA (2)

DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCM toluene THF dioxane MeCN DCE DCE DCE DCE DCE

25 25 25 25 25 25 25 25 40 60 80 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60

12 12 12 12 12 6.5 7 6 4 3 1.5 3 4 4 5 4 4 5 4 6 5 4 4 6 4.5 3

10c 25 0c,d NRc,e 40c 68 57 49 74 80 77 65d 60d 51d 70 77 70 53 68 57 42d 52 61 62 73 79

a

Reaction conditions: 3-(3-phenylprop-2-yn-1-ylidene)pentane-2,4-dione 1a (0.2 mmol), PhI(OAc)2, catalyst, base, solvent (2 mL), N2. bIsolated yield. cMaterial was recovered. dUnknown byproduct was formed. eNo reaction occurred.

For this goal, some screening to expand to other metal species may prove necessary to find new systems. Among optional metals, the use of silver species has less been exploited.14 For example, Pattenden et al. reported that AgNO3-assisted cyclization of enynone precursors provide 2-alkenylfuran.14b However, the method for synthesis of 2-alkenylfuran is suitable only for conjugated enynone with a leaving group (such as hydroxyl, alkoxy group) at the 6-position (Scheme 1d). As a continuation of our work,15 we herein describe AgOAc/ PhI(OAc)2-mediated tandem reactions for the formation of 2alkenylfuran starting from general ene-yne-ketones (Scheme 1e). The ene-yne-ketone substrates 1a−1zc (a mixture of major Eand minor Z-isomers with different carbonyl or sulfuryl groups) were easily prepared via Knoevenagel condensation of conjugated yne-aldehydes with active methylene compounds.16 Pure E-isomers (1b−1m, 1p, 1r, 1s, 1u, 1v, and 1x) were obtained by careful column chromatography isolation and were employed in our study (except for 1q). In the initial stages of this investigation, 3-(3-phenylprop-2-ynylidene)pentane-2,4-dione 1a was selected as the substrate to establish a reaction system for synthesis of 2-alkenylfuran based on the above-mentioned protocol. The results are summarized in Table 1. The treatment of 1a with AgOAc (20 mol %) in 1,2-dichloroethane (DCE) at 25 °C under nitrogen afforded only a trace of the expected 2alkenylfuran 2a (Table 1, entry 1). Triethylamine (TEA) (1.5

equiv) slightly increased the yield (Table 1, entry 2). In the case of using only PhI(OAc)2, no expected product 2a was formed, and only a trace of unknown side product was produced (Table 1, entry 3). In the PhI(OAc)2/TEA system, no reaction occurred (Table 1, entry 4). We were delighted to find that in the AgOAc/ PhI(OAc)2 system, 2a was obtained in 40% yield (Table 1, entry 5). TEA (1.5 equiv) as additive further improved reaction efficiency (Table 1, entry 6). Encouraged by this result, several bases were then tested (Table 1, entries 7 and 8). We found that Et3N provided 2a in the highest yield and with 100% Eselectivity (Table 1, entry 6). The elevation of reaction temperature facilitated to shorten reaction time and also resulted in an increased yield (Table 1, entries 9 and 10). However, higher temperature (up to 80 °C) did not result in an increased yield (Table 1, entry 11). Through further inspection of Ag(I) compound, we found that AgOAc was best suitable for this transformation (Table 1, entries 10 and 12−14). The effect of the amount of AgOAc on the reaction was then explored. Less than 20 mol % AgOAc is not disadvantageous to the reaction because of longer reaction time for completion (Table 1, entries 15 and 16). By screening solvents, we found that DCE afforded the highest yield (Table 1, entries 10 and 17−21). Both the increase and decrease of the amount of PhI(OAc)2 obviously reduced the yield (Table 1, entries 22 and 23); however, the reason is not clear at present. B

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Organic Letters

isomer of product 2d could be obtained by column chromatography. It must be pointed out that E/Z isomer separation is very difficult because of their similarity in polarity (2c, 2l, and 2m; Scheme 2); accordingly, the E/Z ratio had to be determined by 1H NMR spectroscopy. When the R2 group was changed to a more hindered phenyl group, the product 2n was obtained with 100% E-selectivity, albeit in decreased yield. Subsequently, we examined substrates containing cycloalkyl groups (R3) at the alkyne moiety. In the case of R3 = cyclohexyl and cyclopentyl groups, the treatment with AgOAc/PhI(OAc)2/Et3N under the optimized conditions also gave the expected products in yields of 52−70% (2o−v, Scheme 2). The above experimental results show that, in all cases of different carbonyl group-containing substrates 1, the corresponding products 2 were formed based on their Econfiguration rather than the nucleophilicity of carbonyl oxygen of the ketones. Regretfully, no reaction was carried out under the standard conditions when R3 is a cyclopropyl group (2w−x, Scheme 2). Originally, we suspected that the alkalinity of TEA is too weak to bring the anticipated reaction, and therefore strong base was examined. Surprisingly, the cyclization−ketalization event occurred cleanly in the presence of MeONa at 60 °C in MeOH to furnish ketal 3a−c in 60−72% yields (Scheme 3).

The effect of the amount of TEA on the reaction was then investigated. As expected, the use of less than 1.5 equiv of TEA provided lower yield of 2a because of poor reactivity (Table 1, entries 24 and 25); however, the employment of 2 equiv of TEA did not improve the reaction based on reactivity and yield (Table 1, entry 26). Thus, the optimal conditions for the formation of 2-alkeylfuran were obtained as follows: the use of AgOAc (20 mol %) as catalyst, DCE as solvent, and 1.5 equiv of Et3N as base, 2 equiv of PhI(OAc)2 as additive at 60 °C under nitrogen (Table 1, entry 10). With the optimized reaction conditions, the substrate scope for the formation of 2-vinylfurans 2 was exploited by employing 1 (Scheme 2). In the case of R3 = C6H13, the influence of the R1 group, which is adjacent to the alkene moiety, was explored first. This reaction showed high functional group tolerance (2a−n, Scheme 2). 100% E-Selectivity in the reaction was observed except for 2c, 2d, 2l, and 2m. However, the reduction of stereoselectivity cannot be rationalized at present. Pure E and ZScheme 2. Scope of Enynones in AgOAc/PhI(OAc)2/TEAMediated Cyclization−Olefinationa,b

Scheme 3. Cyclization−Ketalization

On the basis of these investigations and reports in the literature,4−14 a plausible mechanism to rationalize this cyclization−olefination (Scheme 2) is depicted in Scheme 4. First, the acetylenic carbon−carbon triple bond is activated by the coordination of enynone 1 with the Ag(I) ion.17 Then the Scheme 4. Proposed Plausible Mechanism for Synthesis of 2Vinylfuran

a Reaction conditions: enynone 1 (0.2 mmol), AgOAc (0.04 mmol), PhI(OAc)2 (0.4 mmol), Et3N (0.3 mmol), DCE (2 mL), N2, 60 °C. b Isolated yield. cUnknown product was formed. dUnreacted material was recovered. eThe reaction was carried out at 80 °C. fNo reaction occurred, and material was recovered.

C

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Organic Letters nucleophilic attack of carbonyl oxygen to the silver coordinated alkyne I via 5-exo-dig cyclization gives furylsilver-carbene intermediate III,14b which is a resonance structure of species II. Direct 1,2-H shift of the Ag(I) carbene III could occur to give product 2 (Table 1, entries 1 and 2); however, the reaction rate is obviously lower than that in the presence of PhI(OAc)2 (Table 1, entry 5). We deduce that, in the presence of PhI(OAc)2, the subsequent reaction of the silver-carbene with PhI(OAc)2 affords phenyliodonium ylide intermediate IV (a reverse transformation of phenyliodonium ylide to metal carbenoid) and regenerates AgOAc. Protonation of V, which is a resonance structure of species IV, with H+,18 easily generates iodonium salt VI. β-H Elimination of VI provides 2-vinylfuran 2 accompanied by the formation of PhI, which can be separated out. β-H Elimination of species II via intermediate VII can also afford the desired product 2. Attempts to trap the phenyliodonium ylide intermediate IV with olefins20a and aldehydes20b were unsuccessful (Scheme 5a,b). A reasonable explanation is

Scheme 6. Possible Mechanism for the Formation of Ketal 3

iodine atom of PhI(OAc)2 affords an intermediate VIII.23 Removal of PhI and OAc− from the intermediate VIII provides an oxinium IX. The nucleophilic addition of MeOH to the oxinium IX and subsequent removal of hydrion give the ketal 3. In summary, we have developed a series of valuable silver(I)catalyzed transformations using ene-yne-ketones as material in the presence of PhI(OAc)2/TEA for the first time. An unusual formation of 2-vinylfurans occurred via tandem reactions. Furylsilver carbene and phenyliodonium ylide intermediates are proposed to play the key roles in these transformations. Hopefully this work will open other methods to study the potential of these silver carbene and iodonium ylide species.

Scheme 5. Control Experiment

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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.9b00712. Experimental Section and 1H and 13C NMR spectra for all compounds (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] ORCID

Guisheng Deng: 0000-0002-6132-5648 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (21372071) and Hunan Provincial Natural Science Foundation of China (2016JJ2080).

that the formation and β-H elimination of iodonium salt VI is perhaps faster than the reaction of phenyliodonium ylide IV with carbon−carbon double bond and carbonyl group. The base can promote the β-elimination of iodonium salt VI and intermediate II. The mechanism for the formation of ketal 3 is not clear at present. On the basis of the unusual behaviors of hypervalent iodine,19 we originally suspected that the formation of the ketal 3 may involve intermediates 4 or 5. Control experiments were carried out. No reaction occurred in the absence of PhI(OAc)2 (Scheme 5c). Compounds 4 and 5 did not provide the corresponding product 3a in the system of AgOAc/PhI(OAc)2/MeONa/MeOH (Scheme 5d,e), and no reaction was detected. Therefore, the acetyl group therein is tolerable under this condition although acetophenone could have been converted to α-hydroxy dimethyl acetal in the PhI(OAc)2/ KOH/MeOH system.21 For the mechanism of the formation of ketal 3, we can offer only a simple proposal (Scheme 6). The nucleophilic attack of OMe− to species II produces Ag(I) intermediate VII.22 Subsequent nucleophilic substitution at the

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