Improved Protocols for the Molybdenum-Catalyzed Hydrostannation of Alkynes

Abstract

In the molybdenum-catalyzed hydrostannation of alkynes the addition mode of tributyltin hydride has a strong effect on the outcome of the reaction. Slow addition increases the yield, even if the amount of tributyltin hydride is reduced to only one equivalent. Microwave irradiation speeds up the reaction dramatically, sometimes at the cost of regioselectivity.

alkynes - hydrostannation - microwave - molybdenum - stannanes

References and Notes

1 Hegedus LS. Organische Synthese mit Übergangsmetallen   VCH; Weinheim: 1995. 

2 A comprehensive survey on palladium-catalyzed reactions can be found in: Malleron JL. Fiaud JC. Legros JY. Handbook of Palladium-Catalyzed Organic Reactions   Academic Press; San Diego: 1997. 

3a Heck RF. Palladium Reagents in Organic Synthesis   Academic Press; New York: 1985. 

3b Stille JK. Angew. Chem., Int. Ed. Engl.  1986,  25:  508 ; Angew. Chem. 1986, 98, 504

3c Pereyre M. Quintard JP. Rahm A. Tin in Organic Synthesis   Butterworth; London: 1987. 

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10

Hydrostannations under Slow Addition Conditions; General Procedure To a 1 M solution of the propargylic substrate in anhyd THF was added Mo(CO)₃ (CNt-Bu)₃ (2 mol%) and hydroquinone (5%) and the mixture was heated to 55 °C. A 1 M solution of Bu₃SnH in anhyd THF was added via syringe pump over a period of 7 h under an Ar atmosphere. After additional 5 h at 55 °C the reaction mixture was concentrated. The crude product was purified via column chromatography (hexane-EtOAc-Et₃N).
(2-Tributylstannyl)- N -allyl Phthalimide ( 3c) ¹H NMR (500 MHz, CDCl₃): δ = 0.83 (t, J = 7.3 Hz, 9 H, 4′-H), 0.91 (t, J = 8.2 Hz, J _Sn,H = 51.6 Hz, 6 H, 1′-H), 1.25 (tq, J = 7.3, 7.3 Hz, 6 H, 3′-H), 1.45 (tt, J = 8.2, 7.3 Hz, 6 H, 2′-H), 4.40 (t, J = 1.7 Hz, J _Sn,H = 24.3 Hz, 2 H, 1-H), 5.25 (td, J = 1.6, 1.6 Hz, J _Sn,H = 58.3, 1 H, 3-H), 5.69 (td, J = 1.7, 1.7 Hz, J _Sn,H = 121.7 Hz, 1 H, 3-H), 7.69 (dd, J = 5.4, 3.2 Hz, 2 H, ArH _m ), 7.83 (dd, J = 5.4, 2.7 Hz, 2 H, ArH _o ). ¹³C NMR (125 MHz, CDCl₃): δ = 9.5 (J _{1 ′,Sn} = 340.7 Hz), 13.6, 27.3 (J _{3 ′,Sn} = 58.5 Hz), 29.0 (J _{2 ′,Sn} = 20.2 Hz), 45.7, 123.2, 125.4, 132.2, 133.9, 147.4, 168.0. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -38.8. Anal. Calcd for C₂₃H₃₅NO₂Sn: C, 58.01; H, 7.41; N, 2.94. Found: C, 58.16; H, 7.66; N, 2.89.
Selected analytical data for the (E)-vinyltin isomer: δ = 4.30 (dd, J = 5.0, 1.3 Hz, 2 H, 1-H), 5.95 (dt, J = 18.9, 5.0 Hz, 1 H, 2-H), 6.13 (dt, J = 18.9, 1.4 Hz, J _Sn,H = 66.8 Hz, 1 H, 3-H). ¹³C NMR (125 MHz, CDCl₃): δ = 42.9, 117.7, 140.2. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -45.9.
p -Nitrophenyl-(2-tributylstannyl)allylether ( 3d) ¹H NMR (500 MHz, CDCl₃): δ = 0.85 (t, J = 7.4 Hz, 9 H, 4′-H), 0.93 (t, J = 8.2 Hz, J _Sn,H = 53.3 Hz, 6 H, 1′-H), 1.28 (tq, J = 7.4, 7.4 Hz, 6 H, 3′-H), 1.47 (tt, J = 7.7, 7.7 Hz, 6 H, 2′-H), 4.74 (t, J = 1.6 Hz, J _Sn,H = 29.6 Hz, 2 H, 1-H), 5.39 (td, J = 1.6, 1.6 Hz, J _Sn,H = 58.0 Hz, 1 H, 3 _cis -H), 5.96 (td, J = 1.9, 1.9 Hz, J _Sn,H = 123.5 Hz, 1 H, 3 _cis -H), 6.92 (d, J = 9.1 Hz, 2 H, ArH _m ), 8.17 (d, J = 9.1 Hz, 2 H, ArH _o ). ¹³C NMR (125 MHz, CDCl₃): δ = 9.8 (J _{1 ′,Sn} = 333.8 Hz), 13.7, 27.2 (J _{3 ′,Sn} = 58.2 Hz), 29.0 (J _{2 ′,Sn} = 20.0 Hz), 75.9, 114.8, 125.9, 126.4, 141.4, 150.0, 163.7. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -40.3. Anal. Calcd for C₂₁H₃₅NO₃Sn: C, 53.87, H, 7.53; N, 2.99. Found: C, 54.02; H, 7.86; N, 2.98.
Selected analytical data for the (E)-vinyltin isomer: δ = 4.64 (dd, J = 4.9, 1.4 Hz, 2 H, 1-H), 6.12 (dt, J = 19.2, 4.9 Hz, 1 H, 2-H), 6.37 (dt, J = 19.2, 1.5 Hz, J _Sn,H = 65.2 Hz, 1 H, 3-H). ¹³C NMR (125 MHz, CDCl₃): δ = 9.5, 27.2, 71.9, 133.8, 141.0. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -45.3.

11 Kazmaier U. Wesquet AO. Synlett  2005,  1271 

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13

A CEM Discover microwave oven was used.

For some representative examples of microwave-assisted cross-couplings and one-pot hydrostannation/Stille coupling reactions:

14a Larhed M. Hallberg A. J. Org. Chem.  1996,  61:  9582 

14b Olofsson K. Kim S.-Y. Larhed M. Curran DP. Hallberg A. J. Org. Chem.  1999,  64:  4539 

14c Maleczka RE. Lavis JM. Clark DH. Gallagher WP. Org. Lett.  2000,  2:  3655 

15

Hydrostannation under Microwave Irradiation; General Procedure A mixture of propargylic substrate (1.5-2.5 mmol), Mo(CO)₃ (CNt-Bu)₃ (5 mol%) and hydroquinone (10 mol%) was dissolved in anhyd THF (5 mL) in a flame-dried flask, then Bu₃SnH (1.1 equiv) was added. After the flask was sealed under a dry argon atmosphere, the solution was heated in a microwave oven for 5-10 min at 100-250 W. After cooling, the reaction mixture was concentrated and the residue purified by chromatography (hexanes-EtOAc) to obtain the desired product as a colorless oil.
Caution! The rapid increase in temperature and pressure may result in an explosion, therefore the microwave-assisted reactions should only be repeated in vessels with a suitable septum as a pressure-relief device.

16

2-(2-Tributylstannylprop-2-ene-1-sulfonyl)pyridine ( 3f) ¹H NMR (500 MHz, CDCl₃): δ = 0.86 (t, J = 7.4 Hz, 9 H, 4′-H), 0.96 (t, J = 8.2 Hz, J _Sn,H = 52.7 Hz, 6 H, 1′-H), 1.27 (tq, J = 7.4, 7.4 Hz, 6 H, 3′-H), 1.41-1.49 (m, 6 H, 2′-H), 4.24 (d, J = 1.3 Hz, J _Sn,H = 39.7 Hz, 2 H, 1-H), 5.36 (d, J = 1.9 Hz, J _Sn,H = 51.1 Hz, 1 H, 3-H), 5.69 (dt, J = 1.9, 1.3 Hz, J _Sn,H = 117.9 Hz, 1 H, 3-H), 7.49 (ddd, J = 7.7, 4.7, 1.6 Hz, 1 H, Ar-H _p ), 7.88 (ddd, J = 7.7, 7.7, 1.9 Hz, 1 H, Ar-H _m ), 7.96 (dd, J = 7.7, 1.6 Hz, 1 H, Ar-H _o ), 8.72 (dd, J = 4.7, 1.9 Hz, 1 H, Ar-H _{m ′}). ¹³C NMR (125 MHz, CDCl₃): δ = 10.4 (J _{1 ′,Sn} = 338.8 Hz), 13.6, 27.3 (J _{3 ′,Sn} = 59.5 Hz), 28.8 (J _{2 ′,Sn} = 20.2 Hz), 61.6 (J _1,Sn = 34.6 Hz), 122.8, 127.1, 136.2 (J _3,Sn = 19.2 Hz), 137.6, 140.9, 150.1, 156.8. ¹¹⁹Sn NMR (74.7 MHz, CDCl₃): δ = -35.1. HRMS (CI⁺): m/z calcd for C₁₆H₂₆NO₂S¹²⁰Sn [M -Bu]⁺: 416.0706; found: 416.0683. HRMS (CI⁺): m/z calcd for C₁₆H₂₆NO₂S¹¹⁸Sn [M - Bu]⁺: 414.0700; found: 414.0689.
Selected analytical data for the (E)-vinyltin isomer:
¹H NMR (500 MHz, CDCl₃): δ = 4.16 (dd, J = 6.7, 1.2 Hz, 2 H, 1-H), 5.84 (dt, J = 18.9, 6.7 Hz, J _Sn,H = 57.7 Hz, 1 H, 2-H), 6.16 (dt, J = 18.9, 1.2 Hz, J _Sn,H = 62.4 Hz, 1 H, 3-H). ¹³C NMR (125 MHz, CDCl₃): δ = 59.6, 122.9, 127.1, 132.3, 137.6, 150.1, 143.2. ¹¹⁹Sn NMR (74.7 MHz, CDCl₃): δ = -48.0.
(2-Tributylstannylprop-2-ene-1-sulfanyl)benzene ( 3g) ¹H NMR (500 MHz, CDCl₃): δ = 0.86 (t, J = 7.3 Hz, 9 H, 4′-H), 0.93 (t, J = 8.2 Hz, J _Sn,H = 52.3 Hz, 6 H, 1′-H), 1.24-1.32 (m, 6 H, 3′-H), 1.43-1.50 (m, 6 H, 2′-H), 3.77 (dd, J = 1.3, 1.3 Hz, J _Sn,H = 39.7 Hz, 2 H, 1-H), 5.19 (dt, J = 2.2, 1.3 Hz, J _Sn,H = 56.7 Hz, 1 H, 3-H), 5.82 (dt, J = 2.2, 1.3 Hz, J _Sn,H = 124.7 Hz, 1 H, 3-H), 7.12 (tt, J = 7.3, 1.0 Hz, 1 H, Ar-H _p ), 7.21-7.28 (m, 4 H, Ar-H _o , Ar-H _m ). ¹³C NMR (125 MHz, CDCl₃): δ = 10.0 (J _{1 ′,Sn} = 328.0 Hz), 13.7, 27.4 (J _{3 ′,Sn} = 57.2 Hz), 29.1 (J _{2 ′,Sn} = 18.2 Hz), 44.2 (J _1,Sn = 44.4 Hz), 125.6, 127.4 (J _3,Sn = 25.0 Hz), 128.6, 128.9, 136.8, 150.0. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -41.5.
Selected analytical data for the (E)-vinyltin isomer:
¹H NMR (500 MHz, CDCl₃): δ = 3.59 (d, J = 5.7, Hz, 2 H, 1-H), 5.94 (dt, J = 18.8, 5.7 Hz, J _Sn,H = 59.3 Hz, 1 H, 2-H), 6.02 (d, J = 18.8 Hz, J _Sn,H = 68.1 Hz, 1 H, 3-H). ¹³C NMR (125 MHz, CDCl₃): δ = 40.6, 128.6, 130.0, 132.4, 142.8. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -47.0.
4-(2-Tributylstannylprop-2-ene-1-sulfanyl)pyridine ( 3h) ¹H NMR (500 MHz, CDCl₃): δ = 0.84 (t, J = 7.5 Hz, 9 H, 4′-H), 0.91 (t, J = 8.2 Hz, J _Sn,H = 52.9 Hz, 6 H, 1′-H), 1.26 (tq, J = 7.5, 7.5 Hz, 6 H, 3′-H), 1.38-1.50 (m, 6 H, 2′-H), 3.82 (dd, J = 1.4, 1.4 Hz, J _Sn,H = 34.6 Hz, 2 H, 1-H), 5.29 (dt J = 1.9, 1.4 Hz, J _Sn,H = 55.4 Hz, 1 H, 3-H), 5.95 (dt, J = 1.9, 1.4 Hz, J _Sn,H = 120.6 Hz, 1 H, 3-H), 7.06 (dd, J = 4.7, 1.6 Hz, 2 H, Ar-H _o ), 8.32 (dd, J = 4.7, 1.6 Hz, 2 H, Ar-H _m ). ¹³C NMR (125 MHz, CDCl₃): δ = 10.0 (J _{1 ′,Sn} = 332.1 Hz), 13.6, 27.3 (J _{3 ′,Sn} = 58.5 Hz), 29.0 (J _{2 ′,Sn} = 20.2 Hz), 41.4 (J _1,Sn = 45.1 Hz), 121.0, 128.3 (J _3,Sn = 24.0 Hz), 148.6, 148.8, 149.0. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -39.7. HRMS (CI⁺): m/z calcd for C₁₆H₂₆NS¹²⁰Sn [M - Bu]⁺: 384.0808; found: 384.0854. HRMS (CI⁺): m/z calcd for C₁₆H₂₆NS¹¹⁸Sn [M - Bu]⁺: 382.0802; found: 382.0817.
Selected analytical data for the (E)-vinyltin isomer:
¹H NMR (500 MHz, CDCl₃): δ = 3.66 (dd, J = 6.0, 1.5 Hz, 2 H, 1-H), 5.93 (dt, J = 18.7, 6.0 Hz, J _Sn,H = 57.4 Hz, 1 H, 2-H), 6.26 (dt, J = 18.7, 1.5 Hz, J _Sn,H = 65.9 Hz, 1 H, 3-H). ¹³C NMR (125 MHz, CDCl₃): δ = 37.1, 121.1, 134.1, 140.8, 149.1. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -45.4.
1-(2-Tributylstannylprop-2-ene-1-sulfanyl)-2,3,4,5,6-pentafluorobenzene ( 3i) ¹H NMR (500 MHz, CDCl₃): δ = 0.87 (t, J = 7.4 Hz, 9 H, 4′-H), 0.95 (t, J = 8.2 Hz, J _Sn,H = 49.8 Hz, 6 H, 1′-H), 1.29 (tq, J = 7.4, 7.4 Hz, 6 H, 3′-H), 1.35-1.49 (m, 6 H, 2′-H), 3.69 (s, J _Sn,H = 41.2 Hz, 2 H, 1-H), 5.11 (d, J = 1.9 Hz, J _Sn,H = 53.2 Hz, 1 H, 3-H), 5.61 (d, J = 1.9 Hz, J _Sn,H = 119.2 Hz, 1 H, 3-H). ¹³C NMR (125 MHz, CDCl₃): δ = 9.9 (J _{1 ′,Sn} = 332.1 Hz), 13.6, 27.4 (J _{3 ′,Sn} = 59.5 Hz), 29.0 (J _{2 ′,Sn} = 19.2 Hz), 44.8 (J _1,Sn = 42.2 Hz), 128.6 (J _3,Sn = 24.0 Hz), 136.3-136.8 (m), 138.5-138.9 (m), 139.8-140.2 (m), 141.9-142.2 (m), 146.3-146.6 (m), 148.2-148.5 (m), 148.9. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -40.2.
Selected analytical data for the (E)-vinyltin isomer:
¹H NMR (500 MHz, CDCl₃): δ = 3.48 (d, J = 5.4 Hz, 2 H, 1-H), 5.75-5.95 (m, 2 H, 2-H, 3-H). ¹³C NMR (125 MHz, CDCl₃): δ = 40.9, 134.1, 141.7. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -47.8.
1-(Allyloxymethylvinyl)tributylstannane ( 3k) ¹H NMR (500 MHz, CDCl₃): δ = 0.87 (t, J = 7.3 Hz, 9 H, 4′-H), 0.90 (t, J = 8.2 Hz, J _Sn,H = 52.3 Hz, 6 H, 1′-H), 1.29 (tq, J = 7.3, 7.3 Hz, 6 H, 3′-H), 1.44-1.51 (m, 6 H, 2′-H), 3.93 (ddd, J = 5.4, 1.5, 1.5 Hz, 2 H, 1′′-H), 4.08 (dd, J = 1.6, 1.6 Hz, J _Sn,H = 34.1 Hz, 2 H, 1-H), 5.14 (ddt, J = 10.4, 1.5, 1.5 Hz, 1 H, 3′′-H), 5.24 (ddt, J = 17.3, 1.5, 1.5 Hz, 1 H, 3′′-H), 5.24 (dt, J = 2.7, 1.6 Hz, J _Sn,H = 61.8 Hz, 1 H, 3-H), 5.84 (dt, J = 2.7, 1.6 Hz, J _Sn,H = 130.8 Hz, 1 H, 3-H), 5.89 (ddt, J = 17.3, 10.4, 5.4 Hz, 1 H, 2′′-H). ¹³C NMR (125 MHz, CDCl₃): δ = 9.6 (J _{1 ′,Sn} = 333.0 Hz), 13.7, 27.4 (J _{3 ′,Sn} = 55.7 Hz), 29.1 (J _{2 ′,Sn} = 20.2 Hz), 71.0, 77.5 (J _1,Sn = 34.5 Hz), 116.5, 124.6 (J _3,Sn = 20.2 Hz), 134.9, 152.9. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -44.6. Anal. Calcd for C₁₈H₃₆OSn: C, 55.84; H, 9.37. Found: C, 55.71; H, 8.95. HRMS (FAB⁺): m/z calcd for C₁₄H₂₇O¹²⁰Sn [M - Bu]⁺: 331.1084; found: 331.1148. HRMS (FAB⁺): m/z calcd for C₁₄H₂₇O¹¹⁸Sn [M - Bu]⁺: 329.1078; found: 329.1090.
Selected analytical data for the (E)-vinyltin isomer:
¹H NMR (500 MHz, CDCl₃): δ = 3.96 (ddd, J = 5.7, 1.4, 1.4 Hz, 2 H, 1′′-H), 3.99 (dd, J = 5.1, 1.3 Hz, 2 H, 1-H), 5.16 (ddt, J = 10.2, 1.6, 1.4 Hz, 1 H, 3′′-H), 5.26 (ddt, J = 16.8, 1.6, 1.4 Hz, 1 H, 3′′-H), 5.91 (ddt, J = 16.8, 10.2, 5.7 Hz, 1 H, 2′′-H), 6.04 (dt, J = 19.2, 5.1 Hz, J _Sn,H = 62.1 Hz, 1 H, 2-H), 6.20 (dt, J = 19.2, 1.3 Hz, J _Sn,H = 71.9 Hz, 1 H, 3-H). ¹³C NMR (125 MHz, CDCl₃): δ = 71.0, 74.0, 117.0, 131.3, 134.9, 144.5. ¹¹⁹Sn NMR (186.5 MHz, CDCl₃): δ = -47.3.