Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Nickel-Catalyzed Reductive Bis-Allylation of Alkynes Kimihiro Komeyama,* Yuta Yamahata, and Itaru Osaka Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University, Higashi, Hiroshima City 739-8527, Japan S Supporting Information *
ABSTRACT: A reductive nickel-catalyzed bis-allylation of alkynes with allyl acetates has been developed, leading to 1,4,7triene skeletons. This reductive bis-allylation proceeds under mild conditions and exhibits good functional group tolerance in both the allyl acetates and the alkynes.
T
development of methods that seek to alleviate these limitations has recently attracted considerable attention. Further, the transition metal-catalyzed reductive coupling of organohalides has been considered an alternative approach for the formation of carbon−carbon bonds that circumvent the use of organometallic reagents. Among these processes, the nickelcatalyzed homo- and cross-couplings between organohalides have been extensively investigated to synthesize aryl−aryl,2 alkyl−alkyl,3 and aryl−alkyl4 compounds (Scheme 1, eq 2). These reductive couplings take advantage of the unique valence-change ability of nickel complexes,2a,3a,d,4c which enables the introduction of two organic functions into the metal center through a process involving two oxidative additions of organohalides. Thus, the reduction of the oxidatively generated organonickel(II) intermediate A produces the active organonickel(I) species B, which undergoes a second oxidative addition producing an organonickel(III) active species in order to perform the final reductive elimination step (Scheme 1, eq 2). Since organonickel A is renowned to be a common intermediate in the formation of the alkenyl transition metal species that are involved in the aforementioned carbometalation of alkynes (Scheme 1, eq 1) and on the basis of our previous work in this field,5 we envisaged that this kind of nickel catalyst could be utilized to perform the reductive bisfunctionalization of alkynes with organohalides under reducing conditions. In this study, we report a nickel-catalyzed reductive bis-allylation of terminal and internal alkynes with allyl acetates in the presence of a zinc reductant to produce 1,4,7-triene frameworks in a stereoselective manner, as illustrated in Scheme 2.6 To evaluate the suitable reaction conditions we initially performed the bis-allylation using 5-cyanohept-1-yne (2a) and allyl acetate 1a as model substrates. The results obtained are depicted in Table 1. When 2a was treated using 1a (2.0 equiv) in the presence of Ni(OAc)2·4H2O (10 mol %), bipyridine (bpy, 20 mol %), and LiCl (1.0 equiv), bis-allylated product 3a was obtained as a single isomer in a 23% yield (Table 1, entry
he development of regio- and stereoselective methodologies for the preparation of multisubstituted olefins has been extensively explored until now, which is mainly due to their usefulness in the direct synthesis of physiologically active molecules and organic materials. Among the existing protocols for the synthesis of multisubstituted olefins, the transition metal-catalyzed carbometalation of alkynes is considered to be one of the most flexible and promising methods, in which an in situ generated organotransition metal catalyst (R−[M]cat) is subsequently trapped using a carbon electrophile, E+ (Scheme 1, eq 1).1 Although a diverse set of analogous protocols for the Scheme 1
synthesis of stereodefined multisubstituted olefins have been developed, a common drawback is the requirement for organometallic reagents, which are generally prepared using the corresponding organohalides in a separate step. Furthermore, the application of such methods is often restricted to substrates without other electrophilic parts due to the high nucleophilicity of the organometallic reagents. Accordingly, the © XXXX American Chemical Society
Received: January 23, 2018
A
DOI: 10.1021/acs.orglett.8b00235 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Scheme 2. Nickel-Catalyzed Reductive Bis-Allylation of Alkynes
Table 2. Scope and Limitation of the Substrates
Table 1. Screening of Reaction Conditions
entry
[Ni]cat
additive
solvent
3a, GC yield (%)
1 2 3 4 5 6a 7b 8a 9a 10a 11a,d
Ni(OAc)2·4H2O Ni(OAc)2·4H2O Ni(OAc)2·4H2O Ni(OAc)2·4H2O Ni(OAc)2·4H2O Ni(OAc)2·4H2O Ni(OAc)2·4H2O NiCl2 NiBr2 Ni(acac)2 Ni(acac)2
LiCl none LiCl LiCl LiCl LiCl LiCl LiCl LiCl LiCl LiCl
DMF DMF MeCN THF DMSO DMSO DMSO DMSO DMSO DMSO DMSO
23 trace trace trace 37 55 36 32 62 66 (58)c 22
a 1a (3.0 equiv). b1a (4.0 equiv). cIsolated yield. dMn was used instead of Zn.
1). The stereochemistry of the trisubstituted olefin in 3a was estimated by performing NOE-measurement between the vinylic proton Ha and allylic proton Hb, which indicated that the addition of the two allyl fragments to the alkyne took place in a syn fashion. The use of LiCl as an additive was observed to be essential in the bis-allylation to avoid a drastic decrease in the yield (Table 1, entry 2).7 Further, solvents also exerted a strong influence during the reaction. Thus, MeCN and THF produced negligible amounts of product 3a (Table 1, entries 3 and 4), whereas DMSO proved to be more effective than DMF (Table 1, entry 5). Furthermore, although an increase in the loading of 1a by a maximum equivalent of 3.0 resulted in a slightly higher yield (55%) (Table 1, entry 6), a further increase in the amount of 1a caused the yield to drop (Table 1, entry 7). In addition, other nickel catalysts were tested (Table 1, entries 8−10), and Ni(acac)2 depicted the best performance (Table 1, entry 10). Zn was also found to be the optimal reductant after comparing with Mn (Table 1, entry 11). Finally, other transition metal catalysts such as CoBr2, FeBr2, and PdCl2 were not observed to exhibit any catalytic activity during the bis-allylation process. Using the optimized conditions (Table 1, entry 10), we investigated the substrate scope and limitation of the bisallylation process by examining a variety of alkynes and allyl acetates, as depicted in Table 2. We observed that although the hydroxyl group inhibited the bis-allylation, its protection with tetrahydropyranyl (THP), triisopropylsilyl (TIPS), or benzyl (Bn) produced the corresponding bis-allylated products (3c− 3e) in 58−62% yields. Furthermore, alkynes containing ester (3f), phthalimidyl (3g), and cyano (3a) (Table 1) substituents were well tolerated during the transformation. More hindered
a b
Parentheses value indicates the ratio of stereoisomer (major:minor). But-3-en-2-yl acetate was used.
terminal and internal alkynes produced 3h and 3i in yields of 71% and 53%, respectively. The bis-allylation protocol was B
DOI: 10.1021/acs.orglett.8b00235 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
product. Furthermore, when the reaction of geranyl and neryl acetates with oct-4-yne was carried out in the presence of tertbutyl alcohol (1.0 equiv), the hydroallylation products 4 and 5 were obtained in 60% yields (E/Z = 3:1) and 55% (E/Z = 1:4) yields, respectively, depicting retention of the stereochemistry (Scheme 5). Using an accurate comparison of the 13C NMR
additionally applied to introduce highly substituted allyl groups like geranyl and neryl into terminal and internal alkynes (3j, 3k, and 3l). Additionally, we observed that the stereochemistry of the allylic moieties was mostly retained in the products.8 The remaining internal alkynes were capable of undergoing bisallylation with 2,3-substituted allyl acetates, which causes the production of the corresponding bis-allylated products in good yields (3m−3p). Further, when a branched allyl acetate, but-3en-2-yl acetate, was subjected to the reaction, 3q was obtained in 76% yield with no detectable amount of bis-adducts at the congested carbon, which suggests that the bis-allylation process involved the generation of a π-allylnickel intermediate at some point during the reaction. On the basis of these observations, we propose a plausible mechanism for the nickel-catalyzed bis-allylation of alkynes, which is depicted in Scheme 3. First, the nickel(0) species A
Scheme 5. Ni-Catalyzed Hydroallylation of Alkynes
Scheme 3. Plausible Reaction Mechanism for the Reductive Bis-Allylation Process
spectra of the two product mixtures, it can be concluded that the introduced allylic moiety, and not the formation of the trisubstituted alkenes, is responsible for the observed stereochemistry (see Supporting Information for details). This can further explain the syn selectivity of the bis-allylation process. To summarize, we have developed a stereoselective bisallylation process for terminal and internal alkynes on the basis of the unique valence-change ability of the nickel catalysts. The bis-allylation process exhibited good tolerance toward various functional groups on alkynes and also allowed the double introduction of highly substituted allyl acetates in good yields. Mechanistic studies indicated that the bis-allylation process involves the allylnickelation of alkynes in a syn fashion followed by the reduction using zinc powder and subsequent second oxidative addition of allyl acetates. Thus, a heterobis-allylation process could be envisaged if the nickel is distinguishable between different types of allyl acetates. Unfortunately, this has not been achieved yet. Further mechanistic studies for the development of a diversity-oriented bis-allylation process are currently ongoing in our group.
that was generated due to the reduction of the nickel(II) precatalyst with Zn powder would undergo the oxidative addition of allyl acetate 1 to produce the π-allylnickel(II) intermediate B.3d,9 The insertion of alkyne 2 into the C−Ni bond of B would proceed in a syn fashion to afford vinyl nickel(II) complex C.6,10,11 Subsequent reduction with Zn would produce vinyl nickel(I) D, which is active for the second oxidative addition of 1 that produced vinyl allyl nickel(III) E.12 Further, intermediate E would undergo a reductive elimination to produce the bis-allylated product 3 and halo-nickel(I) F. Finally, the reduction of F would regenerate A. It is worth mentioning that a classical allylzincation/Negishi-coupling protocol could also be invoked as a mechanism to cause the same reactions.13 However, this hypothesis was ruled out after performing a reaction using allylzinc bromide that was prepared from allyl bromide and Zn powder in THF or DMSO (Scheme 4), which did not produce the corresponding bis-allylated
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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.8b00235. Experimental procedure and spectroscopic data (PDF)
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AUTHOR INFORMATION
Corresponding Author
Scheme 4
*E-mail:
[email protected]. ORCID
Kimihiro Komeyama: 0000-0001-7111-2112 Itaru Osaka: 0000-0002-9879-2098 Notes
The authors declare no competing financial interest. C
DOI: 10.1021/acs.orglett.8b00235 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
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ACKNOWLEDGMENTS This study was supported by a Grant-in-Aid for Scientific Research (C) (No. 15K05502) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. This study was partially founded by the Kyoto Techno Science Center.
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REFERENCES
(1) Flynn, A. B.; Ogilvie, W. W. Chem. Rev. 2007, 107, 4698. (2) Aryl−Aryl homocoupling: (a) Percec, V.; Bae, J.-Y.; Zhao, M.; Hill, D. H. J. Org. Chem. 1995, 60, 176. (b) Jutand, A.; Mosleh, A. J. Org. Chem. 1997, 62, 261. Aryl−Aryl cross-coupling: (c) Ackerman, L. K. G.; Lovell, M. M.; Weix, D. J. Nature 2015, 524, 454. (3) Alkyl−Alkyl homocoupling: (a) Goldup, S. M.; Leigh, D. A.; McBurney, R. T.; McGonigal, P. R.; Plant, A. Chem. Sci. 2010, 1, 383. (b) Prinsell, M. R.; Everson, D. A.; Weix, D. J. Chem. Commun. 2010, 46, 5743. Alkyl−Alkyl cross-coupling: (c) Yu, X.; Yang, T.; Wang, S.; Xu, H.; Gong, H. Org. Lett. 2011, 13, 2138. (d) Dai, Y.; Wu, F.; Zang, Z.; You, H.; Gong, H. Chem. - Eur. J. 2012, 18, 808. (e) Xu, H.; Zhao, C.; Qian, Q.; Deng, W.; Gong, H. Chem. Sci. 2013, 4, 4022. (f) Chen, H.; Jia, X.; Yu, Y.; Qian, Q.; Gong, H. Angew. Chem. 2017, 129, 13283. (4) Aryl−Alkyl cross-coupling: (a) Everson, D. A.; Shrestha, R.; Weix, D. J. J. Am. Chem. Soc. 2010, 132, 920. (b) Wang, S.; Qian, Q.; Gong, H. Org. Lett. 2012, 14, 3352. (c) Biswas, S.; Weix, D. J. J. Am. Chem. Soc. 2013, 135, 16192. (d) Everson, D.; Buonomo, J.; Weix, D. J. Synlett 2014, 25, 233. (e) Ackerman, L. K. G.; Anka-Lufford, L. L.; Naodovic, M.; Weix, D. J. Chem. Sci. 2015, 6, 1115. (f) Wang, X.; Wang, S.; Xue, W.; Gong, H. J. Am. Chem. Soc. 2015, 137, 11562. (g) Huihui, K. M. M.; Caputo, J. A.; Melchor, Z.; Olivares, A. M.; Spiewak, A. M.; Johnson, K. A.; DiBenedetto, T. A.; Kim, S.; Ackerman, L. K. G.; Weix, D. J. J. Am. Chem. Soc. 2016, 138, 5016. (h) Komeyama, K.; Ohata, R.; Kiguchi, S.; Osaka, I. Chem. Commun. 2017, 53, 6401. (i) Wang, J.; Zhao, J.; Gong, H. Chem. Commun. 2017, 53, 10180. (5) (a) Komeyama, K.; Okamoto, Y.; Takaki, K. Angew. Chem., Int. Ed. 2014, 53, 11325. (b) Komeyama, K.; Asakura, R.; Fukuoka, H.; Takaki, K. Tetrahedron Lett. 2015, 56, 1735. (6) Nickel-mediated bis-allylation of alkynes using allylindium has been reported in the following literature: Hirashita, T.; Akutagawa, K.; Kamei, T.; Araki, S. Chem. Commun. 2006, 2598. Additionally, lowvalent niobium-promoted bis-allylation of alkynes has been also demonstrated: Ozaki, M.; Obora, Y.; Tada, Y.; Ishii, Y. J. Organomet. Chem. 2013, 741−742, 109. (7) Although the actual role of LiCl adduct is currently unclear, a coordination of LiCl to the acetate group might accelerate the oxidative addition to the nickel. A slight low-field shift of some of the signals of allyl acetate 2a was observed in a 1H NMR monitoring of a mixture of 1a and LiCl (see Supporting Information). (8) Similar retention of the stereochemistry on the olefinic moiety of the allyl group was observed in the nickel-catalyzed stannylation of allyl acetates: Komeyama, K.; Itai, Y.; Takaki, K. Chem. - Eur. J. 2016, 22, 9130. (9) Tan, Z.; Wan, X.; Zang, Z.; Qian, Q.; Deng, W.; Gong, H. Chem. Commun. 2014, 50, 3827. (10) (a) Ikeda, S.-I.; Sato, Y. J. Am. Chem. Soc. 1994, 116, 5975. (b) Ikeda, S.-I.; Cui, D.-M.; Sato, Y. J. Org. Chem. 2002, 59, 6877. (c) Nakao, Y.; Yukawa, T.; Hirata, Y.; Oda, S.; Satoh, J.; Hiyama, T. J. Am. Chem. Soc. 2006, 128, 7116. (11) Dimers, 1,5-dienes, were not obtained in all reactions. However, as the alternative intermediate for the insertion to alkynes, bis-allylNi(II) intermediate might be also considered. (12) Liu, J.; Ren, Q.; Zhang, X.; Gong, H. Angew. Chem., Int. Ed. 2016, 55, 15544. (13) (a) Knochel, P.; Normant, J. F. Tetrahedron Lett. 1984, 25, 1475. (b) Xie, M.; Wang, J.; Gu, X.; Sun, Y.; Wang, S. Org. Lett. 2006, 8, 431.
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DOI: 10.1021/acs.orglett.8b00235 Org. Lett. XXXX, XXX, XXX−XXX
