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Ruthenium hydride catalyzed silylvinylation of terminal alkynes under ethylene atmosphere at 80 psi
Tetrahedron Letters 58 (2017) 4054–4056
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Ruthenium hydride catalyzed silylvinylation of terminal alkynes under ethylene atmosphere at 80 psi Alexandre D.C. Dixon a,⇑, Robert J. Wilson a, Daniel D. Nguyen, Daniel A. Clark ⇑ Department of Chemistry, 1-014 Center for Science and Technology, Syracuse University, Syracuse, NY 13244, United States
a r t i c l e
i n f o
Article history: Received 26 July 2017 Accepted 13 September 2017 Available online 18 September 2017 Keywords: Catalysis Ruthenium hydride Dienes Silylvinylation Oxasilacycle
a b s t r a c t The development of methods for the stereoselective synthesis of polysubstituted 1,3-dienes is a challenge to synthetic chemistry. Herein is reported a selective approach for the synthesis of polysubstituted 1,3dienes using the ruthenium hydride catalyzed intramolecular silylvinylation of alkynes under 80 psi of ethylene gas. This strategy affords a single diene isomer, is applicable to substrates with aryl and alkyl substitution at the propargyl and homopropargyl positions, and has been utilized in the synthesis of 5and 6-membered oxasilacycles. Ó 2017 Elsevier Ltd. All rights reserved.
The stereoselective synthesis of highly substituted conjugated dienes remains a significant challenge in organic synthesis. New synthetic strategies for the construction of these substructures are in high demand due to the prevalence of 1,3-dienes in biologically active molecules and the utility of 1,3-dienes in natural product synthesis.1,2 Among the most common methods in conjugated diene synthesis include Stille and Suzuki coupling, olefin metathesis, and Horner-Wadsworth-Emmons reactions.1,3,4 More recent examples include hydrovinylation of alkynes using ruthenium catalysts.5–9 These methods function well in simple systems, but are not as selective for dienes containing tri- and tetrasubstituted alkenes. Recently our group developed a stereoselective ruthenium hydride catalyzed silylvinylation of internal alkynes, affording highly substituted conjugated dienes (Fig. 1).10–12 High selectivity was achieved starting from a vinylsilicon-tethered homopropargyl alcohol. These tightly arranged oxasilacycles have been used to influence stereoselectivity in studies by several groups with various transition metal catalysts.10,11,13–19 These transformations are 100% atom economical and avoid use of stoichiometric amounts of tin, phosphorus, or halogen precursors commonly employed in traditional cross-coupling approaches to 1,3-dienes. The vinylsilicon moiety posed as an excellent source of ethylene for transposition onto the starting alkyne. Some competitive cycloisomerization did occur to afford 6-membered rings (isomer B, Fig. 1, equation 1) even when using methyl vinyl ketone as an ⇑ Corresponding authors. a
E-mail address: [email protected] (A.D.C. Dixon). These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.tetlet.2017.09.023 0040-4039/Ó 2017 Elsevier Ltd. All rights reserved.
additive to hamper the reactivity of the sensitive ruthenium hydride intermediates (Fig. 1, equation 1).11 Under ethylene atmosphere we observed higher chemoselectivity (vinylation favored over cycloisomerization), however some stereochemical deterioration was observed (Fig. 1, equation 2).10 Interestingly, upon increasing the pressure of ethylene, a reversal of stereoselectivity was obtained in several substrates. Presumably formation of Z-olefin intermediate III is more rapid under higher pressures of ethylene, and subsequent ethylene insertion outcompetes the isomerization that leads to E-diene II (Fig. 2). Given the utility of this transformation, a streamlined approach toward the selective syn-silylvinylation of terminal alkynes was investigated (Fig. 1, equation 3). Initial optimization began with ruthenium hydride M1 in toluene under 80 psi of ethylene gas. The catalyst displayed full conversion while reaching 40% crude yield after 24 h (Table 1, entry 1). Along with toluene, other conventional solvents used in organometallic reactions were chosen. DCE and THF proceeded in 45% and 60% yield after 24 and 23 h, respectively (Table 1, entries 2 and 3). 1,4-Dioxane was also screened, but only reached 33% crude yield after 24 h (Table 1, entry 4). Reaction in toluene at 60 °C for 3 h yielded 68% of the desired product (Table 1, entry 5). 2-Methyltetrahydrofuran (MeTHF) and cyclopentylmethyl ether (CPME) were also screened; neither reaction reached full conversion after 23 and 18 h respectively, displaying 48% and 21% crude yield (Table 1, entries 6 and 7). Unsatisfied by these results, we increased the catalyst loading and temperature, hoping to enhance the efficiency of the reaction. Ruthenium hydride catalysts have been reported to isomerize
4055
A.D.C. Dixon et al. / Tetrahedron Letters 58 (2017) 4054–4056
Fig. 3.
Table 2 Catalyst and temperature screen.
Fig. 1.
a
Fig. 2.
Table 1 Solvent screen.
Entry a
1 2a 3a 4a 5a 6a 7a 8b 9b 10b 11b a b c
Solvent
Temp (°C)
Time (h)
Yieldc
PhMe DCE THF 1,4-Dioxane PhMe MeTHF CPME PhMe 1,4-Dioxane MeTHF CPME
80 80 60 60 60 50 60 110 110 110 110
24 24 23 24 3 23 18 0.5 0.5 0.5 0.5
40 45 60 33 68 48 21 52 67 40 65
Reaction conditions: Alkyne (0.3 mmol), RuH (2 mol%), solvent (0.2 M). RuH (5 mol%), solvent (0.1 M). Crude yield measured by 1H NMR mesitylene internal standard.
1,3-dienes11,13,15,20 and polymerize alkenes at high temperature.21 We looked to counteract this by decreasing the reaction time. Stopping the reaction in toluene at 110 °C after only 0.5 h achieved a crude yield of 52% (Table 1, entry 8). Reaction in dioxane proceeded smoothly with a crude yield of 67% (Table 1, entry 9). Reaction in MeTHF provided poor results (Table 1, entry 10), but CPME displayed promising reactivity (65%) after only 0.5 h (Table 1, entry
Entry
Catalyst
Temp (°C)
Time (h)
Yield 7aa
1 2 3 4 5 6 7 8 9
M1 M2 M3 M4 M5 M1 M1 M1 M1
110 110 110 110 110 100 90 80 70
0.5 0.5 0.5 0.5 0.5 0.5 0.5 1 2
65 21 52 44 55 73 76 81 79
Crude yield measured by 1HNMR mesitylene internal standard.
11). Initial optimization showed that reaction in CPME at 110 °C after 0.5 h was most effective, while these conditions utilized a green solvent.22 Previous results with bis-phosphino ruthenium catalysts showed little improvement from complex M1 (Fig. 3). However, catalyst M2-M5 were examined and compared to complex M1 (Table 2). Surprisingly, complex M2 reacted with alkyne 1a but only produced 21% of the desired diene 2a (Table 2, entry 2). Hydride catalysts M3-M5 (Table 2, entries 3–5) performed admirably, though the reactivity was not as effective as that with catalyst M1. Incrementally decreasing the reaction temperature improved the crude reaction yield (Table 2, entries 6–8). After 1 h, full conversion was reached at 80 °C, with an 81% crude yield (Table 2, entry 8). Lowering the temperature to 70 °C did not increase yield, even after 2 h of reaction time (Table 2, entry 9). The substrate scope of the transformation was then investigated (Table 3). The instability of these dienes to flash column chromatography on silica gel was somewhat problematic and affected the isolated yields, which were appreciably lower than the crude yields observed by 1H NMR. We obtained 58% isolated yield of biaryl substrate 2a, compared to 81% crude yield observed by 1H NMR with mesitylene internal standard. Increased substitution at the propargyl (2b and 2c) and homopropargyl (2d and 2e) positions appeared to enhance the stability of the dienes on silica. We believe this is the case because the resulting steric hinderance prevents formation of unwanted elimination byproducts during purification. Substrates 2b and 2c were therefore isolated in more satisfactory 82% and 75% yields, respectively. Cyclohexyl substituted 2d was isolated in 55% yield and substrate 2e was isolated in 60% yield. Substrates with less substitution at the propargyl and homopropargyl positions were less stable and lower isolated yields were often observed. 4-methylphenyl substituted 2f and 4-chlorophenyl substituted 2g were isolated in 45% and 38% yield, respectively. N-Pentyl substituted 2h was isolated in 49% yield. A diminished yield for 2h may have been observed due to its volatil-
4056
A.D.C. Dixon et al. / Tetrahedron Letters 58 (2017) 4054–4056 Table 3 Substrate scope.a
a
Isolated yields.
ity. The six-membered oxasilacycle 2i was obtained in 58% yield, though it yielded an inseparable mixture of stereoisomers as a 9.1:1 Z:E ratio. The 2-furyl substituted substrate 2j was isolated in 18% yield and rapidly decomposed when exposed to silica. In conclusion, the Z-selective intramolecular ruthenium hydride catalyzed synthesis of conjugated 1,3-dienes was demonstrated, proceeding via 5-exo-dig cyclizations. The method exploited the use of a vinylsilicon tether, displaying high Z-selectivity within the tightly prearranged system. This method was amenable to several substrates, including alkyl and aryl substituted homopropargyl vinylsilanes, to make 5- and 6- membered oxasilacycles. Acknowledgements
References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
We are grateful to the donors of the ACS PRF (DNI 50787) and the NSF (Career CHE-1352432) for generous financial support. We thank the Chisholm and Totah research groups (Syracuse University) for copious sharing of chemicals, instrumentation, and pertinent discussions. We thank Prof. John Chisholm for his help in preparing this manuscript. A. Supplementary data
13. 14. 15. 16. 17. 18. 19. 20. 21. 22.
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2017.09. 023.
Nicolaou KC, Bulger PG, Sarlah D. Angew Chem Int Ed. 2005;44:4442–4489. Denmark SE, Liu JH-C. Angew Chem Int Ed. 2010;49:2978–2986. 1,3-Dienes; Georg Thieme Verlag; 2009: Vol. 46. Diver ST, Giessert AJ. Chem Rev. 2004;104:1317–1382. Walkowiak J, Jankowska-Wajda M, Marciniec B. Chem Eur J. 2008;14:6679–6686. Nishida M, Adachi N, Onozuka K, Matsumura H, Mori M. J Org Chem. 1998;63:9158–9159. Neisius NM, Plietker B. Angew Chem Int Ed. 2009;48:5752–5755. Kakiuchi F, Uetsuhara T, Tanaka Y, Chatani N, Murai S. J Mol Catal A: Chem. 2002;182–183:511–514. Mori M, Tanaka D, Saito N, Sato Y. Organometallics. 2008;27:6313–6320. Wilson RJ, Kaminsky L, Ahmed I, Clark DA. J Org Chem. 2015;80:8290–8299. Liu S, Zhao J, Kaminsky L, Wilson RJ, Marino N, Clark DA. Org Lett. 2014;16:4456–4459. Wilson RJ. Ruthenium Catalyzed Silylvinylation of Alkynes. Syracuse University; 2015. Zhao J, Liu S, Marino N, Clark DA. Chem Sci. 2013;4:1547–1551. Kaminsky L, Clark DA. Org Lett. 2014;16:5450–5453. Kaminsky L, Wilson RJ, Clark DA. Org Lett. 2015;17:3126–3129. Denmark SE, Pan W. Org Lett. 2002;4:4163–4166. O’Malley SJ, Leighton JL. Angew Chem Int Ed. 2001;40:2915–2917. Denmark SE, Pan W. Org Lett. 2003;5:1119–1122. Anderson EA, Bracegirdle S. Chem Soc Rev. 2010;39:4114–4129. Clark JR, Griffiths JR, Diver ST. J Am Chem Soc. 2013;135:3327–3330. Ogo S, Uehara K, Abura T, Watanabe Y, Fukuzumi S. Organometallics. 2004;23:3047–3052. Watanabe K, Yamagiwa N, Torisawa Y. Org Process Res Dev. 2007;11:251–258.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Ruthenium hydride catalyzed silylvinylation of terminal alkynes under ethylene atmosphere at 80 psi Alexandre D.C. Dixon a,⇑, Robert J. Wilson a, Daniel D. Nguyen, Daniel A. Clark ⇑ Department of Chemistry, 1-014 Center for Science and Technology, Syracuse University, Syracuse, NY 13244, United States
a r t i c l e
i n f o
Article history: Received 26 July 2017 Accepted 13 September 2017 Available online 18 September 2017 Keywords: Catalysis Ruthenium hydride Dienes Silylvinylation Oxasilacycle
a b s t r a c t The development of methods for the stereoselective synthesis of polysubstituted 1,3-dienes is a challenge to synthetic chemistry. Herein is reported a selective approach for the synthesis of polysubstituted 1,3dienes using the ruthenium hydride catalyzed intramolecular silylvinylation of alkynes under 80 psi of ethylene gas. This strategy affords a single diene isomer, is applicable to substrates with aryl and alkyl substitution at the propargyl and homopropargyl positions, and has been utilized in the synthesis of 5and 6-membered oxasilacycles. Ó 2017 Elsevier Ltd. All rights reserved.
The stereoselective synthesis of highly substituted conjugated dienes remains a significant challenge in organic synthesis. New synthetic strategies for the construction of these substructures are in high demand due to the prevalence of 1,3-dienes in biologically active molecules and the utility of 1,3-dienes in natural product synthesis.1,2 Among the most common methods in conjugated diene synthesis include Stille and Suzuki coupling, olefin metathesis, and Horner-Wadsworth-Emmons reactions.1,3,4 More recent examples include hydrovinylation of alkynes using ruthenium catalysts.5–9 These methods function well in simple systems, but are not as selective for dienes containing tri- and tetrasubstituted alkenes. Recently our group developed a stereoselective ruthenium hydride catalyzed silylvinylation of internal alkynes, affording highly substituted conjugated dienes (Fig. 1).10–12 High selectivity was achieved starting from a vinylsilicon-tethered homopropargyl alcohol. These tightly arranged oxasilacycles have been used to influence stereoselectivity in studies by several groups with various transition metal catalysts.10,11,13–19 These transformations are 100% atom economical and avoid use of stoichiometric amounts of tin, phosphorus, or halogen precursors commonly employed in traditional cross-coupling approaches to 1,3-dienes. The vinylsilicon moiety posed as an excellent source of ethylene for transposition onto the starting alkyne. Some competitive cycloisomerization did occur to afford 6-membered rings (isomer B, Fig. 1, equation 1) even when using methyl vinyl ketone as an ⇑ Corresponding authors. a
E-mail address: [email protected] (A.D.C. Dixon). These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.tetlet.2017.09.023 0040-4039/Ó 2017 Elsevier Ltd. All rights reserved.
additive to hamper the reactivity of the sensitive ruthenium hydride intermediates (Fig. 1, equation 1).11 Under ethylene atmosphere we observed higher chemoselectivity (vinylation favored over cycloisomerization), however some stereochemical deterioration was observed (Fig. 1, equation 2).10 Interestingly, upon increasing the pressure of ethylene, a reversal of stereoselectivity was obtained in several substrates. Presumably formation of Z-olefin intermediate III is more rapid under higher pressures of ethylene, and subsequent ethylene insertion outcompetes the isomerization that leads to E-diene II (Fig. 2). Given the utility of this transformation, a streamlined approach toward the selective syn-silylvinylation of terminal alkynes was investigated (Fig. 1, equation 3). Initial optimization began with ruthenium hydride M1 in toluene under 80 psi of ethylene gas. The catalyst displayed full conversion while reaching 40% crude yield after 24 h (Table 1, entry 1). Along with toluene, other conventional solvents used in organometallic reactions were chosen. DCE and THF proceeded in 45% and 60% yield after 24 and 23 h, respectively (Table 1, entries 2 and 3). 1,4-Dioxane was also screened, but only reached 33% crude yield after 24 h (Table 1, entry 4). Reaction in toluene at 60 °C for 3 h yielded 68% of the desired product (Table 1, entry 5). 2-Methyltetrahydrofuran (MeTHF) and cyclopentylmethyl ether (CPME) were also screened; neither reaction reached full conversion after 23 and 18 h respectively, displaying 48% and 21% crude yield (Table 1, entries 6 and 7). Unsatisfied by these results, we increased the catalyst loading and temperature, hoping to enhance the efficiency of the reaction. Ruthenium hydride catalysts have been reported to isomerize
4055
A.D.C. Dixon et al. / Tetrahedron Letters 58 (2017) 4054–4056
Fig. 3.
Table 2 Catalyst and temperature screen.
Fig. 1.
a
Fig. 2.
Table 1 Solvent screen.
Entry a
1 2a 3a 4a 5a 6a 7a 8b 9b 10b 11b a b c
Solvent
Temp (°C)
Time (h)
Yieldc
PhMe DCE THF 1,4-Dioxane PhMe MeTHF CPME PhMe 1,4-Dioxane MeTHF CPME
80 80 60 60 60 50 60 110 110 110 110
24 24 23 24 3 23 18 0.5 0.5 0.5 0.5
40 45 60 33 68 48 21 52 67 40 65
Reaction conditions: Alkyne (0.3 mmol), RuH (2 mol%), solvent (0.2 M). RuH (5 mol%), solvent (0.1 M). Crude yield measured by 1H NMR mesitylene internal standard.
1,3-dienes11,13,15,20 and polymerize alkenes at high temperature.21 We looked to counteract this by decreasing the reaction time. Stopping the reaction in toluene at 110 °C after only 0.5 h achieved a crude yield of 52% (Table 1, entry 8). Reaction in dioxane proceeded smoothly with a crude yield of 67% (Table 1, entry 9). Reaction in MeTHF provided poor results (Table 1, entry 10), but CPME displayed promising reactivity (65%) after only 0.5 h (Table 1, entry
Entry
Catalyst
Temp (°C)
Time (h)
Yield 7aa
1 2 3 4 5 6 7 8 9
M1 M2 M3 M4 M5 M1 M1 M1 M1
110 110 110 110 110 100 90 80 70
0.5 0.5 0.5 0.5 0.5 0.5 0.5 1 2
65 21 52 44 55 73 76 81 79
Crude yield measured by 1HNMR mesitylene internal standard.
11). Initial optimization showed that reaction in CPME at 110 °C after 0.5 h was most effective, while these conditions utilized a green solvent.22 Previous results with bis-phosphino ruthenium catalysts showed little improvement from complex M1 (Fig. 3). However, catalyst M2-M5 were examined and compared to complex M1 (Table 2). Surprisingly, complex M2 reacted with alkyne 1a but only produced 21% of the desired diene 2a (Table 2, entry 2). Hydride catalysts M3-M5 (Table 2, entries 3–5) performed admirably, though the reactivity was not as effective as that with catalyst M1. Incrementally decreasing the reaction temperature improved the crude reaction yield (Table 2, entries 6–8). After 1 h, full conversion was reached at 80 °C, with an 81% crude yield (Table 2, entry 8). Lowering the temperature to 70 °C did not increase yield, even after 2 h of reaction time (Table 2, entry 9). The substrate scope of the transformation was then investigated (Table 3). The instability of these dienes to flash column chromatography on silica gel was somewhat problematic and affected the isolated yields, which were appreciably lower than the crude yields observed by 1H NMR. We obtained 58% isolated yield of biaryl substrate 2a, compared to 81% crude yield observed by 1H NMR with mesitylene internal standard. Increased substitution at the propargyl (2b and 2c) and homopropargyl (2d and 2e) positions appeared to enhance the stability of the dienes on silica. We believe this is the case because the resulting steric hinderance prevents formation of unwanted elimination byproducts during purification. Substrates 2b and 2c were therefore isolated in more satisfactory 82% and 75% yields, respectively. Cyclohexyl substituted 2d was isolated in 55% yield and substrate 2e was isolated in 60% yield. Substrates with less substitution at the propargyl and homopropargyl positions were less stable and lower isolated yields were often observed. 4-methylphenyl substituted 2f and 4-chlorophenyl substituted 2g were isolated in 45% and 38% yield, respectively. N-Pentyl substituted 2h was isolated in 49% yield. A diminished yield for 2h may have been observed due to its volatil-
4056
A.D.C. Dixon et al. / Tetrahedron Letters 58 (2017) 4054–4056 Table 3 Substrate scope.a
a
Isolated yields.
ity. The six-membered oxasilacycle 2i was obtained in 58% yield, though it yielded an inseparable mixture of stereoisomers as a 9.1:1 Z:E ratio. The 2-furyl substituted substrate 2j was isolated in 18% yield and rapidly decomposed when exposed to silica. In conclusion, the Z-selective intramolecular ruthenium hydride catalyzed synthesis of conjugated 1,3-dienes was demonstrated, proceeding via 5-exo-dig cyclizations. The method exploited the use of a vinylsilicon tether, displaying high Z-selectivity within the tightly prearranged system. This method was amenable to several substrates, including alkyl and aryl substituted homopropargyl vinylsilanes, to make 5- and 6- membered oxasilacycles. Acknowledgements
References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
We are grateful to the donors of the ACS PRF (DNI 50787) and the NSF (Career CHE-1352432) for generous financial support. We thank the Chisholm and Totah research groups (Syracuse University) for copious sharing of chemicals, instrumentation, and pertinent discussions. We thank Prof. John Chisholm for his help in preparing this manuscript. A. Supplementary data
13. 14. 15. 16. 17. 18. 19. 20. 21. 22.
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2017.09. 023.
Nicolaou KC, Bulger PG, Sarlah D. Angew Chem Int Ed. 2005;44:4442–4489. Denmark SE, Liu JH-C. Angew Chem Int Ed. 2010;49:2978–2986. 1,3-Dienes; Georg Thieme Verlag; 2009: Vol. 46. Diver ST, Giessert AJ. Chem Rev. 2004;104:1317–1382. Walkowiak J, Jankowska-Wajda M, Marciniec B. Chem Eur J. 2008;14:6679–6686. Nishida M, Adachi N, Onozuka K, Matsumura H, Mori M. J Org Chem. 1998;63:9158–9159. Neisius NM, Plietker B. Angew Chem Int Ed. 2009;48:5752–5755. Kakiuchi F, Uetsuhara T, Tanaka Y, Chatani N, Murai S. J Mol Catal A: Chem. 2002;182–183:511–514. Mori M, Tanaka D, Saito N, Sato Y. Organometallics. 2008;27:6313–6320. Wilson RJ, Kaminsky L, Ahmed I, Clark DA. J Org Chem. 2015;80:8290–8299. Liu S, Zhao J, Kaminsky L, Wilson RJ, Marino N, Clark DA. Org Lett. 2014;16:4456–4459. Wilson RJ. Ruthenium Catalyzed Silylvinylation of Alkynes. Syracuse University; 2015. Zhao J, Liu S, Marino N, Clark DA. Chem Sci. 2013;4:1547–1551. Kaminsky L, Clark DA. Org Lett. 2014;16:5450–5453. Kaminsky L, Wilson RJ, Clark DA. Org Lett. 2015;17:3126–3129. Denmark SE, Pan W. Org Lett. 2002;4:4163–4166. O’Malley SJ, Leighton JL. Angew Chem Int Ed. 2001;40:2915–2917. Denmark SE, Pan W. Org Lett. 2003;5:1119–1122. Anderson EA, Bracegirdle S. Chem Soc Rev. 2010;39:4114–4129. Clark JR, Griffiths JR, Diver ST. J Am Chem Soc. 2013;135:3327–3330. Ogo S, Uehara K, Abura T, Watanabe Y, Fukuzumi S. Organometallics. 2004;23:3047–3052. Watanabe K, Yamagiwa N, Torisawa Y. Org Process Res Dev. 2007;11:251–258.