10598 | Chem. Commun., 2018, 54, 10598--10601 This journal is©The Royal Society of Chemistry 2018

Cite this:Chem. Commun., 2018,

54, 10598

Palladium-catalyzed sequential three-componentreactions to access vinylsilanes†

Bo Zhou, Ailan Lu, Changdong Shao, Xinda Liang and Yanghui Zhang *

A palladium-catalyzed sequential three-component reaction has

been developed. The palladacycles, generated through cascade

reactions of aryl halides and alkynes, are the key intermediates

and react with hexamethyldisilane to form disilylated products. The

reaction represents a useful preparative method for vinylsilanes,

and the vinylsilanes can be transformed into tetrasubstituted

alkenes.

Metallacycles are a very important class of organometalliccompounds.1 They are very common intermediates in transition-metal catalysis. For example, a number of transition-metal-catalyzed C–H functionalization reactions involve metallacyclesas key intermediates.2 Over the past several decades, metalla-cycles have been extensively studied. In this context,C,C-palladacycles are particularly intriguing.3 C,C-Palladacyclesconsist of a C–Pd–C bonding motif and contain two C–Pd bonds.Due to their unique structures, C,C-palladacycles may exhibitnovel reactivity. More importantly, the presence of two C–Pdbonds offers opportunities to develop new transformations bycapitalizing on the unique reactivity and structures of thesespecies.

Currently, the most common route for the synthesis ofC,C-palladacycles is by Pd-catalyzed intramolecular C–H activation.For this method, aryl halides are usually utilized as startingmaterials, and palladacycles are formed through intramolecularC–H activation (Scheme 1a).4 However, for this method, since thepalladacycles are obtained directly from the Pd-mediated cycliza-tion of the substrates, the substrates essentially have the samemolecular composition and level of structural complexity as thepalladacycles to be synthesized, typically necessitating multi-stepsyntheses of the starting materials. It is highly desirable to develop

new protocols that employ simple substrates to accessC,C-palladacycles.

C,C-Palladacycles can also be prepared from aryl halides andalkynes (Scheme 1b). This method represents a straightforwardmethod for the construction of C,C-palladacycles from relativelysimple precursors. Although the reactions of the C,C-palladacyclesobtained through this method have been reported, almost all ofthem are intramolecular cyclization reactions,5 and intermolecularvariants are particularly rare. Although an intermolecular arylationreaction by aryl iodides has been developed, the aryl iodideswere also the starting materials forming the C,C-palladacycles.6

Furthermore, the styrenylpalladium intermediates formed by thereaction of aryl halides and alkynes may continue reacting with thealkynes.5b These reactions indicate that it should be quite achallenge to functionalize C,C-palladacycles obtained through thecascade reactions with other external reagents. The reactionsinvolve multiple reactants, intermediates, and steps, and overallare complicated systems. To make the reactions occur as desired,each step should proceed in a well-defined sequence.

Our group have been interested in the difunctionalizationof the two C–Pd bonds in C,C-palladacycles. Recently, ithas been found that C,C-palladacycles could be disilylatedby hexamethyldisilane,7 which represents one of the fewPd-catalyzed C–H silylation reactions.8 The reactions were

Scheme 1 Synthesis of C,C-palladacycles.

School of Chemical Science and Engineering, Shanghai Key Laboratory of Chemical,

Assessment and Sustainability, Tongji University, 1239 Siping Road, Shanghai,

200092, P. R. China. E-mail: zhangyanghui@tongji.edu.cn;

Web: http://zhangyhgroup.tongji.edu.cn

† Electronic supplementary information (ESI) available. CCDC 1845058. For ESIand crystallographic data in CIF or other electronic format see DOI: 10.1039/c8cc05254a

Received 30th June 2018,Accepted 27th August 2018

DOI: 10.1039/c8cc05254a

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unusually efficient and had broad substrate scope. Furthermore,the two trimethylsilyl groups were incorporated into the pallada-cycles. Inspired by this novel reaction, we envisioned that theC,C-palladacycles formed through the cascade reactions of arylhalides and alkynes could also be disilylated with hexamethyl-disilane. Herein, we report the intermolecular disilylation reactionof C,C-palladacycles generated with aryl halides and alkynes. Thereaction represents a useful preparative method for vinylsilanesand the vinylsilanes can be transformed into tetrasubstitutedalkenes.

We first chose iodobenzene 1a and 1,2-diphenylethyne 2afor constructing C,C-palladacycle, and investigated its silylatingreaction with hexamethyldisilane 3 (Table 1). Gratefully,disilylated product 4aa was formed in 67% yield in the presenceof 1 equivalent of K2CO3 even using 1 equivalent of 2a and 3and 1 mol% of Pd(OAc)2 (entry 1). Although the roles of K2CO3

in the reaction remain to be investigated, it has been reportedthat K2CO3 may scavenge the iodide ligand and promotePd-catalyzed C–H activation.9 The yield was improved to over80% by increasing the quantity of 3 or Pd(OAc)2 (entries 2 and 3),and a yield of 96% was obtained by using 2 equivalents of 3 and5 mol% of Pd(OAc)2 (entry 4).

Subsequently, we investigated the substrate scope of thedisilylation reaction. We first examined the reaction of 4-iodoanisole1b. The reaction was also high-yielding. Unfortunately, two isomers4ba and 4ba0 were formed (Table 2, entry 1). The structure of themajor isomer was confirmed by X-ray crystallography. Theformation of isomer 4ba’ should result from cis/trans isomeriza-tion of the vinyl palladium intermediate. Next, we sought tosuppress the formation of 4ba0. We first screened a range ofligands, and found that the addition of ligands failed to improveisomeric ratios (entries 2–5). Fortunately, the formation of 4ba0

was almost completely suppressed and the yield of the desiredproduct 4ba was improved to 97% by using 1 equivalent ofMe4NOAc (entry 8). The reason remains to be investigated.Notably, vinylsilanes are valuable intermediates in organicsynthesis.10 One of the challenges is to control stereoselectivityin the preparation of vinylsilanes.11 The reaction that we developed

represents a new method for the synthesis of vinylsilanes in highstereoselectivity.

The performance of various substituted iodobenzenes wasthen studied under the optimal conditions for the disilylationreactions (Table 3). A range of para-substituted iodobenzeneswere suitable and the yields were almost quantitative for4ca–4ea. The yields were good or moderate for 4fa–4ha. meta-Substituted derivatives were also compatible (4ia–4ka). A rangeof disubstituted iodobenzenes underwent the cascade reactionsmoothly (4la–4oa). In the reaction of 1o, the product resultingfrom cis/trans isomerization of the vinylpalladium intermediatewas formed (4oa). Even sterically hindered substrates bearingan ortho-substituent could be transformed into the corres-ponding disilylated products in high yields (4pa–4ua). Notably,

Table 1 Optimization of reaction conditions for the disilylation reactionof the C,C-palladacycle with hexamethyldisilane

Entry Pd(OAc)2 (mol%) TMS–TMS (equiv.) Yielda (%)

1 1 1 672 1 2 843 5 1 894 5 2 96(92b)

a The yields were determined by 1H NMR analysis of the crude reactionmixture using CHCl2CHCl2 as the internal standard. b Yield of theisolated product. DMF = N,N-dimethylformamide, TMS–TMS = 1,1,1,2,2,2-hexamethyldisilane.

Table 2 Suppression of the formation of the isomer for the disilylationreaction of 4-iodoanisole and 1,2-diphenylethyne

EntryAdditive(equiv.)

Yielda

(%) EntryAdditive(equiv.)

Yielda

(%)

1 — 86/14 5 P(o-tol)3 (0.2) 74/252 dppm (0.2) 48/20 6 Bu4NBr (1.0) 73/213 PPh3 (0.2) 30/10 7 Bu4NOAc (1.0) 49/154 BINAP (0.2) 35/17 8 Me4NOAc (1.0) 97(93%b)/trace

a The yields were determined by 1H NMR analysis of the crude reactionmixture using CHCl2CHCl2 as the internal standard. b Yield of theisolated product. dppm = bis(diphenylphosphino)methane, BINAP =bis(diphenylphosphino)methane, P(o-tol)3 = tri-o-tolylphosphane.

Table 3 Iodobenzene scope of the disilylation reactiona

a Yields of the isolated products. b E/Z ratio.

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10600 | Chem. Commun., 2018, 54, 10598--10601 This journal is©The Royal Society of Chemistry 2018

5-iodo-1H-indole was a suitable substrate, producing a noveltetrasubstituted alkene as the final product (4va). It should bementioned that only a trace amount of isomers was observed byGC-MS for most of the reactions.

The alkyne scope was also investigated (Table 4). A range ofsymmetrical diphenylacetylenes bearing two para- or meta-substituents gave the disilylated products in good or excellentyields. ortho-Substituted diphenylacetylene 2m was also com-petent, albeit in a lower yield (4am). The performance ofunsymmetrical alkynes was also examined. Gratefully, 2-methyl and-propyl phenylacetylenes were suitable (4an/4an0 and 4ao/4ao0).Although two regioisomers were formed, the isomeric ratioswere around 6 : 1 and 10 : 1 for 2n and 2o respectively. To confirmthe structure of the major isomers, the two TMS groups of 4aowere removed with CsF. The 1H and 13C NMR spectra of theresulting product (E)-pent-1-ene-1,2-diyldibenzene were identicalto those reported previously (for detailed experiments see theESI†).

Notably, the alkenyl silyl group of the disilylated productscan be transformed into the bromo and iodo groups selectively(Scheme 2a and b).12 The bromo and iodo groups can be furtherconverted to other functional groups and therefore allow accessto various tetrasubstituted alkenes. Tetrasubstituted alkenesare important constituents in many natural products anddrugs, and they also have important applications in materialsscience.13 However, stereoselective synthesis of tetrasubstitutedalkenes still remains a challenge. Our cascade reaction representsan attractive alternative to traditional carbonyl olefinations andcross-metathesis reactions for the stereoselective synthesis ofacyclic tetrasubstituted alkenes.

A dibrominated product could also be synthesized (2c), andthe alkenyl silyl group could be removed, forming trisubstitutedalkene 8aa (2d). Furthermore, the disilylated products couldbe transformed into silicon-bridged p-conjugated compounds

disiloxanes 9aa (2e). Notably, silicon-bridged p-conjugatedcompounds are widely studied as OLED materials.14

On the basis of the products obtained in the reaction andprevious reports,6a,7 we proposed a mechanism for the disilyla-tion reaction as shown in Scheme 3. The catalytic cycle startswith the oxidative addition of iodobenzenes to Pd(0). Theresulting aryl Pd(II) species A undergo migratory insertion toform vinylPd(II) species B. The subsequent intramolecular C–Hactivation generates C,C-palladacycle C. C reacts with hexam-ethyldisilane via an oxidative addition or metathesis pathway toyield intermediate G or H. Finally, the reductive eliminationgives the disilylated product 4 and releases Pd0 species.In addition, B may undergo cis–trans isomerization to forma second vinylPd(II) species B0,6a which then providesC,C-palladacycle C0. C0 can be disilylated by hexamethyldisilaneto afford minor isomer 40 in the same pathway as that in theformation of desired product 4.

In conclusion, we have developed a palladium-catalyzedsequential three-component reaction. The reaction involvesputative C,C-palladacycles as the key intermediates. Unlikethe common methods for accessing such species from structu-rally complex starting materials, in this case the palladacycles

Table 4 Alkyne scope of the disilylation reactiona

a Yields of the isolated products. b E/Z ratio.

Scheme 2 Transformations of the disilylated products.

Scheme 3 Proposed mechanism for the disilylation reaction.

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were accessed from simple aryl halides and alkynes. Theresulting C,C-palladacycles were difunctionalized by hexamethyl-disilane to form vinylsilanes as the final products. It shouldbe noted that high stereoselectivities were achieved in thereactions and that the disilylated products can be transformedinto other tetrasubstituted alkenes. Further studies towardsunderstanding the detailed mechanism and exploring otherreactions of C,C-palladacycles generated in this way are underwayin our lab.

The work was supported by the National Natural ScienceFoundation of China (No. 216721626 and 2137217) and Scienceand Technology Commission of Shanghai Municipality(14DZ2261100). We thank Prof. Keary M. Engle (The ScrippsResearch Institute) for helpful discussions.

Conflicts of interest

There are no conflicts to declare.

Notes and references1 (a) J. Dupont, C. S. Consorti and S. Spencer, Chem. Rev., 2005,

105, 2527; (b) T. R. Cook and P. Stang, Chem. Rev., 2015, 115, 7001;(c) I. P. Beletskaya and A. V. Cheprakov, J. Organomet. Chem., 2004,689, 4055.

2 (a) L. Ackermann, R. Vicente and A. R. Kapdi, Angew. Chem., Int. Ed.,2009, 48, 9792; (b) T. W. Lyons and M. S. Sanford, Chem. Rev., 2010,110, 1147; (c) G. Song and X. Li, Acc. Chem. Res., 2015, 48, 1007;(d) J. Miao and H. Ge, Eur. J. Org. Chem., 2015, 7859; (e) Y. Zhang,G. Shi and J.-Q. Yu, in Comprehensive Organic Synthesis, ed.P. Knochel and G. A. Molander, Elsevier, Oxford, 2nd edn, 2014,vol. 3, pp. 1101–1209; ( f ) J.-Q. Yu and Z. Shi, C–H Activation,Springer, Berlin, 2010.

3 (a) C. Juan, P. Pilar and C. Ernesto, Coord. Chem. Rev., 1999,193, 207; (b) A. Steffen, R. M. Ward, W. D. Jones and T. B. Marder,Coord. Chem. Rev., 2010, 254, 1950.

4 (a) T. Piou, A. Bunescu, Q. Wang, L. Neuville and J. Zhu, Angew.Chem., Int. Ed., 2013, 52, 12385; (b) J.-X. Yan, H. Li, X.-W. Liu,J.-L. Shi, X. Wang and Z.-J. Shi, Angew. Chem., Int. Ed., 2014, 53, 4945;(c) R. Deng, Y. Huang, X. Ma, G. Li, R. Zhu, B. Wang, Y.-B. Kang andZ. Gu, J. Am. Chem. Soc., 2014, 136, 4472; (d) D.-W. Gao, Q. Yin, Q. Guand S.-L. You, J. Am. Chem. Soc., 2014, 136, 4841; (e) M. Wang,X. Zhang, Y.-X. Zhuang, Y.-H. Xu and T.-P. Loh, J. Am. Chem. Soc.,2015, 137, 1341; ( f ) L. Yang and R. M. Melot, Chem. Sci., 2017,8, 1344; (g) G. Dyker, Angew. Chem., Int. Ed., 1992, 31, 1023;

(h) G. Dyker, Angew. Chem., Int. Ed., 1994, 33, 103; (i) D. Masselotand J. P. H. T. Gallagher, J. Am. Chem. Soc., 2006, 128, 694; ( j ) J. Ye,Z. Shi, T. Sperger, Y. Yasukawa, C. Kingston, F. Schoenebeck andM. Lautens, Nat. Chem., 2016, 9, 361; (k) M. Perez-Gomez andJ.-A. Garcıa-Lopez, Angew. Chem., Int. Ed., 2016, 55, 14389; (l) T.-J. Hu,G. Zhang, Y.-H. Chen, C.-G. Feng and G.-Q. Lin, J. Am. Chem. Soc., 2016,138, 2897; (m) A. Gutierrez-Bonet, F. Julia-Hernandez, B. Luis andR. Martin, J. Am. Chem. Soc., 2016, 138, 6384; (n) D. Chen, G. Shi,H. Jiang, Y. Zhang and Y. Zhang, Org. Lett., 2016, 18, 2130; (o) G. Shi,D. Chen, H. Jiang, Y. Zhang and Y. Zhang, Org. Lett., 2016, 18, 2958;(p) C. Shao, Z. Wu, X. Ji, B. Zhou and Y. Zhang, Chem. Commun., 2017,53, 10429.

5 (a) G. Wu, A. L. Rheingold, S. J. Geib and R. F. Heck, Organometallics,1987, 6, 1941; (b) T. Sakakibara, Y. Tanaka and T.-I. Yamasaki, Chem.Lett., 1986, 797; (c) R. C. Larock, M. J. Doty, Q. Tian and J. M. Zenner,J. Org. Chem., 1997, 62, 7536; (d) Q. Tian and R. C. Larock, Org. Lett.,2000, 2, 3329; (e) M. A. Campo and R. C. Larock, J. Am. Chem. Soc.,2002, 124, 14326; ( f ) J. Zhao, M. Campo and R. C. Larock, Angew.Chem., Int. Ed., 2005, 44, 1873; (g) N. Chernyak, D. Tilly, Z. Li andV. Gevorgyan, Chem. Commun., 2010, 46, 150; (h) C. Wang, S. Rakshitand F. Glorius, J. Am. Chem. Soc., 2010, 132, 14006.

6 (a) G. Dyker and A. Kellner, Tetrahedron Lett., 1994, 35, 7633; (b) Athree-component cross-coupling of aryl halides, alkynes, and arynesmight also involve C,C-palladacycles as the intermediate. However,another mechanism was proposed: Z. Liu and R. C. Larock, Angew.Chem., Int. Ed., 2007, 46, 2535.

7 (a) A. Lu, X. Ji, B. Zhou, Z. Wu and Y. Zhang, Angew. Chem., Int. Ed.,2018, 57, 3233; (b) W. Li, G. Xiao, G. Deng and Y. Liang, Org. Chem.Front., 2018, 5, 1488.

8 (a) K. S. Kanyiva, Y. Kuninobu and M. Kanai, Org. Lett., 2014,16, 1968; (b) C. Chen, M. Guan, J. Zhang, Z. Wen and Y. Zhao,Org. Lett., 2015, 17, 3646; (c) Y.-J. Liu, Y.-H. Liu, Z.-Z. Zhang,S.-Y. Yan, K. Chen and B.-F. Shi, Angew. Chem., Int. Ed., 2016, 55,13859; (d) A. Deb, S. Singh, K. Seth, S. Pimparkar, B. Bhaskararao,S. Guin, R. B. Sunoj and D. Maiti, ACS Catal., 2017, 7, 8171;(e) J.-L. Pan, C. Chen, Z.-G. Ma, J. Zhou, L.-R. Wang and S.-Y.Zhang, Org. Lett., 2017, 19, 5216.

9 M. Lafrance, C. N. Rowley, T. K. Woo and K. Fagnou, J. Am. Chem.Soc., 2006, 128, 8754.

10 (a) E. Langkopf and D. Schinzer, Chem. Rev., 1995, 95, 1375;(b) I. Fleming, A. Barbero and D. Walter, Chem. Rev., 1997, 97, 2063.

11 B. Marciniec, H. Maciejewski, C. Pietraszuk and P. Pawluc, Advancesin Silicon Science, Springer, Berlin, 2009.

12 (a) O. Reiser, Angew. Chem., Int. Ed., 2006, 45, 2838; (b) E.-I. Negishi,Z. Huang, G. Wang, S. Mohan, C. Wang and H. Hattori, Acc. Chem.Res., 2008, 41, 1474; (c) M. Shindo and K. Matsumoto, Top. Curr.Chem., 2012, 327, 1.

13 P. Pawluc and B. Marciniec, Synlett, 2007, 2061.14 (a) H. Kai, J. Ohshita, S. Ohara, N. Nakayama, A. Kunai, I.-S. Lee and

Y.-W. Kwak, J. Organomet. Chem., 2008, 693, 3490; (b) J. Ohshita,K. Murakami, D. Tanaka and H. Yoshida, Heterocycles, 2012, 86, 1167.

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