(Z)-Selective Hydrosilylation of Terminal Alkynes with HSiMe(OSiMe3

Letter pubs.acs.org/OrgLett

(Z)‑Selective Hydrosilylation of Terminal Alkynes with HSiMe(OSiMe3)2 Catalyzed by a Ruthenium Complex Containing an N‑Heterocyclic Carbene Yuichiro Mutoh,* Yusei Mohara, and Shinichi Saito* Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan S Supporting Information *

ABSTRACT: The N-heterocyclic-carbene-ligated ruthenium complex [RuHCl(CO)(H2IMes)(PCy3)] exhibits high catalytic activity for the (Z)-selective hydrosilylation of various terminal alkynes with 1,1,1,3,5,5,5-heptamethyltrisiloxane (HSiMe(OSiMe3)2). The stereoretentive derivatization of the (Z)alkenylsiloxanes allows the synthesis of biologically active compounds, e.g. potent antitumor agents and inhibitors for induced-NO synthase.

Scheme 1. Transition-Metal-Catalyzed β-(Z)-Selective Hydrosilylation of Terminal Alkynes with HSiMe(OSiMe3)2

A

lkenylsilanes have received substantial attention on account of their utility in organic chemistry.1 The hydrosilylation of alkynes using late-transition-metal catalysts represents a reliable and straightforward synthetic route to alkenylsilanes.1,2 As the silane source, the cost-effective HSiMe(OSiMe 3 ) 2 is particularly attractive, 3 given that alkenylsiloxanes derived from HSiMe(OSiMe3)2 are resistant toward hydrolysis due to the siloxane linkages, but still readily undergo Hiyama cross-coupling reactions4 owing to the presence of two electron-withdrawing (trimethylsilyl)oxy groups.3c,f During the hydrosilylation of terminal alkynes, several possible isomers can be produced,1,2 and the β-(E)-selective reaction of terminal alkynes with HSiMe(OSiMe3)2 has been established using well-defined platinum complexes.3a,c However, the β-(Z)-selective reaction with HSiMe(OSiMe3)2 remains challenging with respect to both catalytic efficiency of the transition-metal catalysts, as well as the regio- and stereoselectivity of the products. In fact, the ruthenium−N,Sheterocyclic-carbene-catalyzed hydrosilylation of phenylacetylene with HSiMe(OSiMe3)2 affords a mixture of isomers in low yield (Scheme 1, eq 1),5a while a latent (Z)-to-(E) isomerization was observed when using an Ir−Cr bimetallic catalyst (Scheme 1, eq 2).5b Alternative approaches to (E)- and (Z)alkenylsiloxanes are the dehydrogenative silylation of terminal alkenes with HSiMe(OSiMe3)2,3f,i and the rhodium-catalyzed β-(Z)-selective hydrosilylation of terminal alkynes with HSiMe2(OSiMe3) and HSiMe(OEt)2, which generates the corresponding (Z)-alkenylsiloxanes.6 Considering mechanistic studies7 on the β-(Z)-selective hydrosilylation of alkynes with HSiEt3 catalyzed by [RuHCl(CO)(PCy3)2]8,9 and the Grubbs second generation catalyst system in olefin metathesis,10 we envisioned that [RuHCl(CO)(NHC)(PCy3)],11 which carries an N-heterocyclic © 2017 American Chemical Society

carbene (NHC), should be a highly active catalyst for the hydrosilylation of terminal alkynes (Scheme 1, eq 3). Herein, we describe the [Ru(NHC)]-catalyzed β-(Z)-selective hydrosilylation of terminal alkynes with HSiMe(OSiMe3)2. Initially, we investigated the effect of the structure of NHC in [RuHCl(CO)(NHC)(PCy3)] on the hydrosilylation of phenylacetylene (1a) with HSiMe(OSiMe3)2 (Table 1). When Received: August 10, 2017 Published: September 8, 2017 5204

DOI: 10.1021/acs.orglett.7b02477 Org. Lett. 2017, 19, 5204−5207

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Organic Letters Table 1. Scope of the β-(Z)-Selective Hydrosilylation of 1a with HSiMe(OSiMe3)2 Regarding Ruthenium Complexesa

entry

[RuHCl(CO)(L)(PCy3)]

time (h)

yield (%)b

β-(Z)/ β-(E)c

1 2 3 4 5

[RuHCl(CO)(PCy3)2] [RuHCl(CO)(H2IMes)(PCy3)] [RuHCl(CO)(H2IPr)(PCy3)] [RuHCl(CO)(IMes)(PCy3)] [RuHCl(CO)(IPr)(PCy3)]

1 0.5 1 1 1

34 95 89 78 80

97:3 >99:1 >99:1 >99:1 >99:1

Scheme 2. Scope of the [RuHCl(CO)(H2IMes)(PCy3)]Catalyzed β-(Z)-Selective Hydrosilylation with Respect to Terminal Alkynes 1a

a Reaction conditions: [RuHCl(CO)(L)(PCy3)] (1 mol %), 1a (1.1 equiv), HSiMe(OSiMe3)2 (1.0 equiv), CH2Cl2 (0.1 M). In all cases, the α-isomer was not detected by GC-MS or 1H NMR spectroscopy. b Isolated yields. cThe β-(Z)/β-(E) ratio was estimated by 1H NMR analysis of the crude product.

bis(phosphine) complex [RuHCl(CO)(PCy3)2] was used as the catalyst, and the reaction was conducted at room temperature for 1 h, styrylsiloxane 2a was obtained in low yield as a mixture of isomers (Table 1, entry 1). The corresponding H 2 IMes-ligated complex [RuHCl(CO)(H2IMes)(PCy3)] was more active and furnished β-(Z)-2a in 95% yield as a single stereoisomer after 0.5 h (Table 1, entry 2). A ruthenium complex with a bulkier H2IPr ligand also exhibited good performance (Table 1, entry 3). Although decreased catalytic activity was observed for ruthenium complexes containing unsaturated NHC ligands, the stereoselectivity of the products was nearly perfect (Table 1, entries 4 and 5). In general, complexes of the type [RuHCl(CO)(NHC)(PCy3)] are efficient precatalysts for the (Z)-selective hydrosilylation of terminal alkynes with HSiMe(OSiMe3)2. Considering the mechanistic studies on the hydrosilylation of terminal alkynes with HSiEt3,7 the NHCs should affect the ratelimiting dissociation and recoordination of PCy3 for all intermediates, e.g. [RuCl{SiMe(OSiMe 3) 2 }(CO)(NHC)(PCy3)]. The lower efficacy of the complexes bearing unsaturated NHCs in the hydrosilylation is consistent with the results obtained from Grubbs second generation catalyst system in olefin metathesis, which involves a rate-determining dissociation of PCy3.12 These results suggest that saturated NHCs favor the liberation of PCy3 from a resting-state 16electron complex to generate the active 14-electron species such as [RuCl{SiMe(OSiMe3)2}(CO)(H2IMes)] during the hydrosilylation. The observed high stereoselectivity of the hydrosilylation could be attributed to the steric bulk of the NHC-ligated ruthenium complex. Even when the less bulky HSiMe2Ph was employed in the [RuHCl(CO)(H2IMes)(PCy3)]-catalyzed hydrosilylation of phenylacetylene, the corresponding product was also obtained in a Z/E ratio of 99:1. Use of the less bulky ruthenium catalysts such as [RuHCl(CO)(Pi-Pr3)2] and [RuHCl(CO)(PCy3)2] in the hydrosilylation with HSiMe2Ph afforded Z/E product ratios of 97:3 and 96:4, respectively.8 To explore the scope of this reaction with respect to the substrates, various terminal alkynes were used to afford the corresponding alkenylsilanes with excellent (Z)-selectivity (Scheme 2). Under the established conditions, 4-substituted

a

General reaction conditions: [RuHCl(CO)(H2IMes)(PCy3)] (1 mol %), 1 (1.1 equiv), HSiMe(OSiMe3)2 (1.0 equiv), CH2Cl2 (0.1 M). Unless otherwise specified, the Z/E ratio (>99:1) was based on the 1H NMR analysis of the crude product. Isolated yields are shown in parentheses. bThe reaction was conducted at 70 °C in toluene.

(Z)-styrylsiloxanes 2b and 2c were obtained in high yields. Trifluoromethyl-substituted phenylacetylene (1d) exhibited a comparatively low reactivity, albeit 2d was formed in 96% yield when the reaction was performed at 70 °C. This decreased reactivity may be rationalized in terms of a weaker coordinating ability of the alkyne to the ruthenium center. Notably, the bromo functionality is tolerated in this hydrosilylation, and the corresponding products (2e−g) were obtained regardless of the position of the bromine atom on the benzene ring. The relatively low reactivity in the reaction leading to 2g is probably due to steric congestion. The compatibility of heteroaryl-substituted terminal acetylenes such as ethynylthiophenes (1h and 1i) and 2-ethynylbenzofurane (1j) was also evaluated, as the reactivity of ethynylheteroaromatics in the hydrosilylation reaction has not yet been documented. The reactions were generally sluggish, but 2h−j were obtained diastereoselectively in high yields without the need to increase the catalyst loading. The reaction of 4-ethynylcoumarin (1k), a bulkier cyclic ester with an alkyne moiety, reached completion after 60 h at 70 °C to afford (Z)-2k as the major product. Longer reaction times and/or higher temperatures were required for the reactions of 1h−k, given that these alkynes contain sulfur and oxygen atoms, which are able to coordinate to the ruthenium center. The oxygen atom 5205

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Organic Letters

stereospecific access to biologically relevant (Z)-stilbene derivatives.

in 1j and 1k may act as a directing group that leads to the formation of α-isomers.9b,13 In addition to aryl-substituted alkynes, alkyl-substituted alkynes also underwent this stereospecific hydrosilylation. The reaction of 1-hexyne (1l) at room temperature yielded 2l in 90% after 24 h. The hydrosilylation of an alkyne derived from dimethyl malonate furnished the corresponding product (2m) in 60% yield after 14 h at 70 °C. Again, the relatively low yield of this reaction should be attributed to the steric demand of the substrate and the coordination ability of the functional group. Finally, the synthetic utility of 2 was explored by synthesizing biologically active compounds. We examined the fluoride-free Hiyama cross-coupling3f,14 of 2 with 3,4,5-trimethoxyiodobenzene (Scheme 3, eq 1). The reaction proceeded in

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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.7b02477. Experimental procedures (PDF) X-ray crystallographic data for [RuHCl(CO)(H2IMes)(PCy3)] (CCDC 1543773) (CIF) [RuHCl(CO)(IPr)(PCy3)] (CCDC 1543774) (CIF) 3b (CCDC 1566459) (CIF)

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Scheme 3. Functionalization of the Obtained Hydrosilylation Productsa

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (Y.M.). *E-mail: [email protected] (S.S.). ORCID

Yuichiro Mutoh: 0000-0002-5254-9383 Shinichi Saito: 0000-0001-8520-1116 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors thank Mr. Yuta Inoue, Dr. Shintaro Kodama, and Prof. Youichi Ishii for elemental analysis measurements (Chuo University).

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REFERENCES

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a

The Z/E ratio (99:1) was estimated based on the 1H NMR analysis of the crude products. Isolated yields are shown in parentheses. Si = SiMe(OSiMe3)2

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