Alkyne Hydrosilylation

Aldrich ChemFiles 2006, 6.5, 3.

[Cp*Ru(MeCN)3]PF6 and Other Catalysts

Vinyl-metal reagents play a pivotal role in organic synthesis. Among the vinyl-metal reagents available, silicon-based reagents are of increasing importance. This is largely due to their low cost, minimal toxicity, ease of handling, and the simplicity of byproduct removal. Particularly attractive is the ability to carry the silyl moiety through a series of synthetic manipulations. Much of the impetus for the growing relevance of vinylsilanes arises from the successful cross-coupling strategies developed for these useful organometallic species. Vinylsilanes are also useful as Michael acceptors in conjugate addition reactions and as masked ketones in Tamao–Fleming oxidations.

Of the available methods for preparation of vinylsilanes, the hydrosilylation of alkynes is the most direct and atom-economical approach (Scheme 1). A number of transition metal catalysts have been devised to execute these reactions in a regio- and stereocontrolled fashion (Figure 1). Methods for hydrosilylation of terminal alkynes were developed some time ago, particularly for the preparation of cis- and trans-β-vinylsilanes. Classical Pt-catalysis (Speier’s1 and Karstedt’s2 catalysts), as well as Rh-based catalysis ([Rh(cod)2]BF4 and [RhCl(nbd)]2 4), remain powerful methods for synthesis of trans-β-vinylsilanes. Wilkinson’s catalyst was also demonstrated to yield the trans product in polar solvents, with the cis isomer predominating in non-polar media.5 Ru-based catalysts (e.g. [Ru(benzene)Cl2]2 or [Ru(p-cymene)Cl2]2) allow for access to cis-β-vinylsilanes.6 Under certain conditions, Grubbs’ 1st generation catalyst also gives cis products, although the stereo- and regioselectivity of the hydrosilylation is highly dependent on the alkyne, silane, and solvent.7 While there exists a wealth of methods for preparation of linear β-vinylsilanes, until recently there were no general methods for the preparation of 1,1-disubstituted α-vinylsilanes.8 Moreover, although selective intramolecular hydrosilylation of internal alkynes can be achieved,9 a selective intermolecular variant was virtually unknown.10 The Trost group at Stanford University developed a remarkably robust protocol for hydrosilylation of terminal acetylenes to give α-vinylsilanes, relying on the ruthenium(II) catalyst, [Cp*Ru(MeCN)3]PF6.11,12 This catalyst also provides a competent method for regioselective intra- and intermolecular hydrosilylation of internal alkynes, giving exclusively Z-trisubstituted alkenes.

Scheme 1.

Figure 1.

back to top

Terminal Alkynes

A diverse set of terminal alkynes underwent rapid and mild hydrosilylation in the presence of [Cp*Ru(MeCN)3]PF6 to give 1,1-disubstituted a-vinylsilanes in good to excellent yield, often with low catalyst loadings (Scheme 2, Table 1). The reaction is tolerant to a wide range of functional groups including halogens, free alcohols, alkenes, internal alkynes, esters, and amines. Moreover, a breadth of silanes can be used in the reaction with excellent predictability.

Scheme 2.

Table 1.

The a-vinylsilanes are useful intermediates that can participate in a host of synthetically valuable transformations. The simplest manipulation, protodesilylation, is achieved by treatment of the vinylsilane with TBAF in the presence of catalytic CuI (Scheme 3).13

Scheme 3.

Internal vinylsilanes are also active towards ring-closing metathesis with Grubbs’ 2nd generation catalyst, yielding silicon-functionalized carbocycles that are amenable to further elaboration (Scheme 4).11 For example, both triethoxysilanes11 and benzyldimethylsilanes14 are active participants in fluoridepromoted, Pd-catalyzed cross-coupling (Schemes 5 and 6).

Scheme 4.

Scheme 5.

Scheme 6.

back to top

Intramolecular Hydrosilylation

Finally, intramolecular hydrosilylation is possible using hydroxyalkynes, as illustrated in the concise synthesis of the 3-hydroxypiperidine alkaloid (+)-spectaline (Scheme 10).16b Treatment of the homopropargyl alcohol with tetramethyldisilazane (TMDS), followed by regio- (distal) and stereoselective (Z) intramolecular hydrosilylation, gave a cyclic azidosiloxane. Tamao–Fleming oxidation followed by reduction with concomitant cyclization gave (+)-spectaline in respectable yield.

Scheme 10.

The sequence of intramolecular hydrosilylation and subsequent cross-coupling provides an excellent method for introducing a new carbon bond at an alkyne carbon that is in a remote position from a free hydroxyl group (Scheme 11).17

Scheme 11.

We are pleased to offer [Cp*Ru(MeCN)3]PF6, as well as a number of other catalysts and silanes for hydrosilylation.

back to top

Internal Alkynes

As illustrated in Scheme 1, non-selective hydrosilylation of internal alkynes would potentially give four isomeric addition products. The Trost group has demonstrated that hydrosilylation of internal alkynes with [Cp*Ru(MeCN)3]PF6 gives trisubstituted Z-vinylsilanes exclusively, as a result of trans addition of the silane to the alkyne (Scheme 7, Table 2).11 Importantly, the hydrosilylation reaction is regioselective as well. The regioselectivity can be summarized as follows: (i) hydrosilylation of 2-alkynes results in the formation of Z-alkenes with the silyl group occupying the less sterically-demanding position (entries 1 and 2); (ii) for substrates where the alkyne is not in the 2-position, the silyl substituent will occupy the more sterically-demanding position in the Z-alkene (entry 4); (iii) for propargylic, homopropargylic, and bishomopropargylic alcohol substrates, hydrosilylation occurs such that the silyl group resides distal to the hydroxyl functionality of the Z-alkene (entries 5–9); (iv) in the case of a,b-alkynylcarbonyls, the silyl group again selectively occupies the distal position of the Z-alkene (entries 10–13).11,15 For free propargylic, homopropargylic, and bishomopropargylic alcohols, hydrosilylation with a silane bearing a leaving group (e.g., an ethoxy substituent) results in the formation of a cyclic siloxane (entries 5 and 8). Significantly, the hydrosilylation using [Cp*Ru(MeCN)3]PF6 can be performed while maintaining the stereochemical integrity of asymmetric centers residing in the alkyne substrate (entry 9).

Scheme 7.

Table 2.

Like a-vinylsilanes, hydrosilylation products resulting from internal addition are active in numerous reaction processes including: protodesilylation, cycloaddition, Tamao–Fleming oxidation, and Pd-catalyzed cross-coupling.14 For example, though non-sterically differentiated alkynes may undergo stereobut non-regioselective hydrosilylation (entry 3), protodesilylation of the product mixture provides a single trans diastereomer.13 Therefore, the hydrosilylation-protodesilylation protocol provides a useful method for alkyne reduction to a trans alkene and is a complement to the cis-selectivity observed in the Lindlar reduction. As shown in Scheme 8, even highly reactive silanes can participate in hydrosilylation reaction, with excellent predictability.11b The resultant alkenylchlorosilane was trapped with a hexadienol to give a siloxane linkage. Heating the triene resulted in an intramolecular Diels-Alder (IMDA) reaction, yielding a siloxane with four contiguous stereocenters. The adduct could then be treated to protodesilylation or Tamao–Fleming conditions to furnish the primary alcohol or the diol respectively.

Scheme 8.

Manipulation of the alkene prior to protodesilylation or oxidation is also feasible. For example, vinylsilanes are readily epoxidized by m-CPBA in a diastereoselective fashion (Scheme 9). Subsequent protodesilylation furnishes the corresponding syn-epoxy alcohol, while Tamao–Fleming oxidation provides a syn-diol. Therefore, this process can be used as a surrogate to the aldol condensation.

Scheme 9.

back to top




  1. For a recent example, see: Denmark, S. E.; Wehrli, D. Org. Lett. 2000, 2, 565.
  2. For recent examples, see: (a) Itami, K. et al. J. Org. Chem. 2002, 67, 2645. (b) Denmark, S. E.; Wang, Z. Org. Lett. 2001, 3, 1073. (c) Denmark, S. E.; Wang, Z. Org. Synth. 2005, 81, 54.
  3. Takeuchi, R. et al. J. Org. Chem. 1995, 60, 3045.
  4. Sato, A. et al. Org. Lett. 2004, 6, 2217.
  5. Takeuchi, R.; Tanouchi, N. J. Chem. Soc., Perkin Trans. 1 1994, 2909.
  6. Na, Y.; Chang, S. Org. Lett. 2000, 2, 1887.
  7. (a) Maifeld, S. V. et al. Tetrahedron Lett. 2005, 46, 105. (b) Menozzi, C. et al. J. Org. Chem. 2005, 70, 10717. (c) Aricó, C. S.; Cox, L. R. Org. Biomol. Chem. 2004, 2, 2558.
  8. While references 7a and 7b illustrate access to a-vinylsilanes using Ph3SiH, the method does not appear to be general. Isomeric mixtures are often formed with other silanes.
  9. For recent examples, see: (a) Denmark, S. E.; Pan, W. Org. Lett. 2003, 5, 1119. (b) Denmark, S. E.; Pan, W. Org. Lett. 2002, 4, 4163. (c) Denmark, S. E.; Pan, W. Org. Lett. 2001, 3, 61.
  10. For a recent example, see: Hamze, A. et al. Org. Lett. 2005, 7, 5625.
  11. (a) Trost, B. M. et al. J. Am. Chem. Soc. 2001, 123, 12726. (b) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2005, 127, 17644.
  12. For a mechanistic rationale of this Ru-catalyzed hydrosilylation, see: Chung, L. W. et al. J. Am. Chem. Soc. 2003, 125, 11578.
  13. Trost, B. M. et al. J. Am. Chem. Soc. 2002, 124, 7922.
  14. Trost, B. M. et al. Org. Lett. 2003, 5, 1895.
  15. Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2004, 126, 13942.
  16. (a) Trost, B. M. et al. Angew. Chem. Int. Ed. 2003, 42, 3415. (b) Trost, B. M. et al. J. Am. Chem. Soc. 2005, 127, 10028. (c) Trost, B. M. et al. Org. Lett. 2005, 7, 4911.
  17. Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2003, 125, 30.

back to top

Related Links