The Cyclopropylmethylsilane Terminated Prins Reaction: Stereoelectronic Controlled Formation of (E)-Skipped Dienes Alcohols and a (Z)-Skipped Diene Modification

Abstract

The reaction of 1-phenyldimethylsilyl-2-vinyl cyclopropane with aldehydes under the influence of dimethylaluminium chloride proceeds smoothly to provide skipped diene alcohols with exclusive E-olefin geometry regardless of the initial cis/trans configuration of the starting cyclopropane. The reaction is under stereoelectronic control where the Prins cation favours an anti-bisected conformation. A syn-bisected conformation can be partially induced by the introduction of a buttressing trimethylsilyl group on the cyclopropane ring, leading to competitive (masked) Z-skipped diene formation.

Prins - skipped dienes - stereoelectronic - buttressing - cyclopropylmethyl cation

References

1 Snider BB. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.527 

2 For the ‘pinacol-terminated Prins reaction’ and its application for the preparation of multifunctional tetrahydrofurans see: Hanaki N. Link JT. MacMillan DWC. Overman LE. Trankle WG. Wurster JA. Org. Lett.  2000,  2:  223 ; and references cited therein

3 Hosomi A. Sakurai H. Tetrahedron Lett.  1976,  16:  1295 

4 Snider BB. Acc. Chem. Res.  1980,  13:  426 

5 Danishefsky SJ. Aldrichimica Acta  1986,  19:  59 

6 Braddock DC. Badine DM. Gottschalk T. Synlett  2001,  1909 

7a Pittman CU. Olah GA. J. Am. Chem. Soc.  1965,  87:  5123 

7b The bisected comformation of the parent cyclopropylmethyl cation has been shown to be 14Kcalmol^-1 more stable than the perpendicular conformation: Kabakoff DS. Nanamworth E. J. Am. Chem. Soc.  1970,  92:  3234 

8

General Procedure: Dimethylalumiumchloride solution, 1 M in hexanes (1.85 mL, 1.85 mmol) was added dropwise to a solution of aldehyde (1.85 mmol) and a 1:1 mixture of cis and trans vinyl cyclopropane 2 (200 mg, 0.92 mmol) in CH₂Cl₂ (4.0 mL), at -78 °C. The pale yellow solution was allowed to warm to r.t. overnight. The reaction was quenched by cautious, dropwise addition of aq HCl (2 M, 4.0 mL), and the biphasic mixture was stirred vigorously for 8 h, diluted with CH₂Cl₂ (10 mL) and sat. brine (10 mL). The CH₂Cl₂ layer was separated and the aq layer was extracted with CH₂Cl₂ (3 × 20 mL). Combined organics were washed with saturated brine (1 × 20 mL), dried (MgSO₄), concentrated and chromatographed (CH₂Cl₂-petroleum ether 40-60 °C) to give the skipped diene alcohol product.

9

Data for compounds 5a-k. Diene 5a: Colourless oil. IR (thin film): 3404 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 5.81 (ddt, 1 H, J = 16.6, 10.2, 6.5 Hz), 5.50 (m, 2 H), 5.00 (m, 2 H), 3.58 (m, 1 H), 2.77 (t, 2 H, J = 6.2 Hz), 2.22 (m, 1 H), 2.07 (m, 1 H), 1.55 (s, 1 H), 1.42 (s, 2 H), 1.26 (s, 8 H), 0.86 (t, 3 H, J = 6.4 Hz). ¹³C NMR (68 MHz, CDCl₃): δ = 136.9, 131.6, 127.4, 115.2, 71.1, 40.7, 36.8, 31.9, 29.4, 25.7, 22.7, 14.1. MS (CI⁺, NH₃): m/z = 214 [M + NH₄]⁺. HRMS (CI) calcd for C₁₃H₂₈NO: [M + NH₄]⁺ 214.2171. Found: [M + NH₄]⁺ 214.2168. Diene 5b: Colourless oil. IR (thin film): 3350 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 5.80 (ddt, 1 H, J = 16.6, 10.2, 6.5 Hz), 5.50 (m, 2 H), 5.00 (m, 2 H), 3.57 (m, 1 H), 2.76 (t, 2 H, J = 6.2 Hz), 2.22 (m, 1 H), 2.07 (m, 2 H), 1.60 (m, 1 H), 1.42 (m, 2 H), 1.25 (m, 14 H), 0.86 (t, 3 H, J = 6.4 Hz). ¹³C NMR (68 MHz, CDCl₃): δ = 136.9, 131.6, 127.4, 115.2, 71.0, 40.8, 36.8, 31.9, 29.7, 29.7, 29.6, 29.4, 25.7, 22.7, 14.1. MS (CI⁺, NH₃): m/z = 256 [M + NH₄]⁺. HRMS (CI) calcd for C₁₆H₃₄NO: [M + NH₄]⁺ 256.2640. Found: [M + NH₄]⁺ 256.2642. Diene 5c: Colourless oil. IR (thin film): 3414 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 5.79 (ddt, 1 H J = 16.6, 10.2, 6.5 Hz), 5.50 (m, 2 H), 5.00 (m, 2 H), 3.32 (m, 1 H), 2.75 (t, 2 H, J = 6.3 Hz), 2.22, (m, 1 H), 2.03 (m, 1 H), 1.64 (m, 2 H), 0.90 (d, 3 H, J = 6.7 Hz), 0.89 (d, 3 H, J = 6.7 Hz). ¹³C NMR (68 MHz, CDCl₃): δ = 136.9, 131.6, 127.8, 115.2, 75.7, 37.6, 36.8, 33.0, 18.8, 17.6. MS (CI⁺, NH₃): m/z = 172 [M + NH₄]⁺. HRMS (CI) calcd for C₁₀H₂₂NO: [M + NH₄]⁺ 172.1701. Found: [M + NH₄]⁺ 172.1705. Diene 5d: Colourless oil. IR (thin film): 3417
cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 5.80 (ddt, 1 H, J = 16.6, 10.2, 6.5 Hz), 5.52 (m, 2 H), 4.99 (m, 2 H), 3.19 (dd, 1 H, J = 10.6, 2.3 Hz), 2.76, (t, 2 H, J = 5.9 Hz), 2.30 (m, 1 H), 1.94 (m, 1 H), 0.90 (s, 9 H). ¹³C NMR (68 MHz, CDCl₃): δ = 136.9, 131.5, 128.9, 115.2, 78.5, 36.8, 35.3, 34.6, 25.8. MS (CI⁺, NH₃): m/z = 186 [M + NH₄]⁺. HRMS (CI) calcd for C₁₁H₂₄NO: [M + NH₄]⁺ 186.1858. Found: [M + NH₄]⁺ 186.1855. Diene 5e: Colourless oil. IR (thin film): 3473, 1736 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 5.79 (ddt, 1 H, J = 16.4, 9.9, 6.2 Hz), 5.49 (m, 2 H), 4.99 (m, 2 H), 4.22 (m, 3 H), 2.74, (m, 3 H), 2.45 (m, 2 H), 1.27 (t, 3 H, J = 7.1). ¹³C NMR (68 MHz, CDCl₃): δ = 174.5, 136.7, 132.3, 124.9, 115.3, 70.3, 61.6, 37.6, 36.7, 14.2. MS (CI⁺, NH₃): m/z = 202 [M + NH₄]⁺ 185 [M + H]⁺. HRMS (CI) calcd for C₁₀H₂₀NO₃: [M + NH₄]⁺ 202.1443. Found: [M + NH₄]⁺ 202.1446. Diene 5f: Colourless oil. IR (thin film): 3398 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 7.33 (m, 5 H), 5.79 (m, 1 H), 5.51 (m, 2 H), 5.01 (m, 2 H), 4.67 (t, 1 H, J = 5.9 Hz), 2.77 (t, 2 H, J = 6.2 Hz), 2.45 (m, 2 H), 2.20 (s, 1 H). ¹³C NMR (68 MHz, CDCl₃): δ = 144.1, 136.9, 132.1, 128.4, 127.5, 127.0, 125.9, 115.3, 73.7, 42.8, 36.8. MS (CI⁺, NH₃): m/z = 188 [M + H]⁺. HRMS (CI) calcd for C₁₃H₂₀NO: [M + NH₄]⁺ 206.1544. Found: [M + NH₄]⁺ 206.1541. Diene 5g: Colourless oil. IR (thin film): 3381 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 7.28 (m, 4 H), 5.77 (ddt, 1 H, J = 17.7, 9.7, 6.2 Hz), 5.55 (dt, 1 H, J = 15.4, 6.2 Hz), 5.40 (m, 1 H), 5.00 (m, 2 H), 4.65 (dd, 1 H, J = 7.6, 5.3 Hz), 2.75 (t, 2 H, J = 5.0 Hz), 2.42 (m, 2 H), 2.10 (s, 1 H). ¹³C NMR (68 MHz, CDCl₃): δ = 142.5, 136.7, 133.1, 132.7, 128.5, 127.3, 126.5, 115.4, 72.9, 42.8, 36.8. MS (CI⁺, NH₃): m/z = 224, 222 [M + H⁺]. HRMS (CI) calcd for C₁₃H₁₉NOCl: [M + NH₄]⁺ 240.1155. Found: [M + NH₄]⁺ 240.1165. Diene 5h: Colourless oil. IR (thin film): 3341
cm^-1. ¹H NMR (CDCl₃, 270 MHz): δ = 7.23 (m, 4 H), 5.78 (m, 1 H), 5.53 (m, 1 H), 5.43 (m, 1 H), 5.00 (m, 2 H), 4.65 (m, 1 H), 2.77 (dd, 2 H, J = 4.9, 7.6 Hz), 2.42 (m, 2 H).
¹³C NMR (CDCl₃, 68 MHz): δ = 146.1, 136.7, 134.3, 132.7, 129.7, 127.6, 126.4, 126.1, 124.0, 115.4, 72.3, 42.8, 36.8. MS (CI⁺, NH₃): m/z = 240, 242 [M + NH₄]⁺. HRMS (CI) calcd for C₁₃H₁₉NOCl: [M + NH₄]⁺ 240.1155. Found: [M + NH₄]⁺ 240.1149. Diene 5i: Colourless oil. IR (thin film): 3385 cm^-1. ¹H NMR (CDCl₃, 270 MHz): δ = 7.53 (d, 1 H, J = 7.5 Hz), 7.25 (m, 3 H), 5.80 (ddt, 1 H, J = 16.6, 10.2, 6.2 Hz), 5.56 (m, 2 H), 5.10 (dd, 1 H, J = 8.1, 3.9 Hz), 5.01 (m, 2 H), 2.78 (m, 2 H), 2.58 (m, 1 H), 2.28 (m, 2 H). ¹³C NMR (CDCl₃, 68 MHz): δ = 141.4, 136.8, 132.4, 131.7, 129.4, 128.4, 127.1, 127.0, 126.7, 115.4, 70.0, 41.0, 36.8. MS (CI⁺, NH₃): m/z = 240, 242 [M + NH₄]⁺. HRMS (CI) calcd for C₁₃H₁₇NCl: [M + NH₄ - H₂O]⁺ 222.1050. Found: [M +
NH₄ - H₂O]⁺ 222.1051. Diene 5j: Yellow oil. IR (thin film): 3409 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 8.15 (d, 2 H, J = 8.6 Hz), 7.47 (d, 2 H, J = 8.6 Hz), 5.74 (m, 1 H), 5.54 (dt, 1 H, J = 15.2, 6.5 Hz), 5.40 (m, 1 H), 5.00 (m, 1 H), 4.98 (m, 2 H), 4.78 (br t, 1 H, J = 5.3 Hz), 2.74 (t, 2 H, J = 5.5 Hz), 2.43 (m, 3 H). ¹³C NMR (68 MHz, CDCl₃): δ = 151.5, 147.1, 136.5, 133.2, 126.6, 125.7, 124.6, 123.5, 115.4, 72.5, 42.7, 36.6. MS (CI⁺, NH₃): m/z = 251 [M + NH₄]⁺. HRMS (CI) calcd for C₁₃H₁₉N₂O₃: [M + NH₄]⁺ 251.1395. Found: [M + NH₄]⁺ 251.1399. Diene 5k: Pale yellow solid. Mp 53-54 °C. IR (DRIFTS): 3555 cm^-1; ¹H NMR (270 MHz, CDCl₃): δ = 7.89 (dd, 1 H, J = 8.2, 1.5 Hz), 7.79 (dd, 1 H, J = 7.9, 1.5 Hz), 7.62 (dt, 1 H, J = 7.4, 1.2), 7.39 (dt, 1 H, J = 8.2, 1.5 Hz), 5.77 (m, 1 H), 5.55 (m, 2 H), 5.27 (m, 1 H), 4.97 (m, 2 H), 2.77 (t, 2 H, J = 6.3 Hz), 2.62 (m, 1 H), 2.41 (m, 2 H). ¹³C NMR (68 MHz, CDCl₃): δ = 147.9, 139.4, 136.6, 133.4, 132.9, 128.2, 128.1, 126.4, 124.4, 115.5, 68.7, 41.8, 36.8. MS (CI⁺, NH₃): m/z = 251 [M + NH₄]⁺. HRMS (CI) calcd for C₁₃H₁₉N₂O₃: [M + NH₄]⁺ 251.1395. Found: [M + NH₄]⁺ 251.1391.

10 Martin M. Synth. Commun.  1983,  13:  809 

11 Using Cu(0)-CuSO₄. For an example see: Wilson SR. Zucker PA. J. Org. Chem.  1988,  53:  4682 

12

An analytically pure sample of ester 11a could be obtained after extensive chromatography: Colourless oil. IR (thin film, NaCl plates): 1711 cm^-1. ¹H NMR (CDCl₃, 270 MHz): δ = 7.51 (m, 2 H), 7.35 (m, 3 H), 4.13 (m, 2 H), 1.26 (t, 3 H, J = 7.2 Hz), 1.09 (m, 3 H), 0.85 (m, 2 H), 0.32 (s, 6 H), 0.00 (s, 9 H). ¹³C NMR (CDCl₃, 68 MHz): δ = 174.1, 139.0, 133.6, 129.0, 127.8, 60.3, 20.5, 19.2, 17.7, 14.7, 14.5, -2.2, -2.8; MS (CI⁺): m/z = 352 [M + NH₄]⁺. HRMS (CI) calcd for C₁₈H₃₄NO₂Si₂: [M + NH₄] 352.2128. Found: [M + NH₄], 352.2133. Anal. Calcd for C₁₈H₃₀O₂Si₂: C, 64.61; H, 9.04. Found: C, 64.53; H, 8.93.

13

Irradiation of the TMS group in alcohol 12a results in enhancements for two cyclopropyl protons. For alcohol 12b only one cyclopropyl proton is enhanced. Relative to the TMS group, this unambiguously places the pendant phenyldimethylsilylmethyl group trans for the former and cis for the latter.

14 Dess DB. Martin JC. J. Am. Chem. Soc.  1991,  113:  7277 

15

Data for silylcyclopropanes 12a,b-14a,b. Alcohol 12a: Colourless oil. IR (thin film): 3300 cm^-1. ¹H NMR (CDCl₃, 400 MHz): δ = 7.56 (m, 2 H), 7.38 (m, 3 H), 3.76 (d, 1 H, J = 11.4 Hz), 3.54 (d, 1 H, J = 11.4 Hz), 1.11 (dd, 1 H, J = 4.0, 13.9 Hz), 0.81 (m, 1 H), 0.78 (dd, 1 H, J = 9.6, 13.9 Hz), 0.65 (dd, 1 H, J = 7.6, 4.4 Hz), 0.38 (s, 3 H), 0.37 (s, 3 H), 0.06 (t, 1 H, J = 4.4 Hz), 0.00 (s, 9 H). ¹³C NMR (CDCl₃, 68 MHz): δ = 139.2, 133.3, 128.8, 127.9, 65.3, 15.8, 15.5, 14.5, 14.1, -2.4, -2.6, -2.9. MS (CI⁺): m/z = 310 [M + NH₄]⁺. HRMS (CI⁺) calcd for C₁₆H₃₂N₁O₁Si₂: [M + NH₄]⁺ 310.2022. Found: [M + NH₄]⁺, 310.2029. Alcohol 12b: Colourless oil. IR (thin film): 3367 cm^-1. ¹H NMR (CDCl₃, 400 MHz): δ = 7.42 (m, 2 H), 7.25 (m, 3 H), 3.62 (d, 1 H, J = 10.8 Hz), 2.73 (d, 1 H, J = 10.8 Hz), 1.22 (dd, 1 H, J = 2.9, 14.4 Hz), 0.64 (m, 1 H), 0.38 (dd, 1 H, J = 11.6, 14.4 Hz), 0.33 (dd, 1 H, J = 4.4, 10.5 Hz), 0.23 (s, 3 H), 0.21 (s, 3 H), 0.10 (t, 1 H, J = 4.4 Hz), 0.00 (s, 9 H). ¹³C NMR (CDCl₃, 68 MHz): δ = 139.3, 133.7, 129.0, 127.8, 72.6, 19.8, 18.1, 15.7, 15.2, 0.0, -2.6, -3.0. MS (CI⁺): m/z = 310 [M + NH₄]⁺. HRMS (CI) calcd for C₁₆H₃₂N₁O₁Si₂: [M + NH₄]⁺ 310.2022. Found: [M + NH₄]⁺, 310.2028. Aldehyde 13a: Colourless oil. ¹H NMR (CDCl₃, 270 MHz): δ = 9.33 (s, 1 H), 7.53 (m, 2 H), 7.39 (m, 3 H), 1.50-1.00 (m, 5 H), 0.36 (s, 6 H), 0.04 (s, 9 H). Aldehyde 13b: Colourless oil. ¹H NMR (CDCl₃, 270 MHz): δ = 8.66 (s, 1 H), 7.54 (m, 2 H), 7.40 (m, 3 H), 1.50-0.52 (m, 5 H), 0.38 (s, 6 H), 0.17 (s, 9 H). Alkene 14a: Colourless oil. IR (thin film): 3069 cm^-1. ¹H NMR (CDCl₃, 270 MHz): δ = 7.55 (m, 2 H), 7.38 (m, 3 H), 5.86 (dd, 1 H, J = 16.9, 10.1 Hz), 5.10 (d, 1 H, J = 10.1 Hz), 4.93 (d, 1 H, J = 16.9 Hz), 1.40-0.30 (m, 5 H), 0.34 (s, 6 H), -0.04 (s, 9 H). ¹³C NMR (CDCl₃, 68 MHz): δ = 139.7, 139.3, 133.7, 128.9, 127.8, 116.5, 18.1, 16.1, 16.0, 15.2, -2.67, -2.71,
-3.2. MS (CI⁺): m/z = 289 [M]. HRMS (CI) calcd for C₁₇H₂₉Si₂: [M + 1]⁺ 289.1808. Found: [M + 1]⁺ 289.1809. Anal. Calcd for C₁₇H₂₈Si₂: C, 70.76; H, 9.78. Found: C, 70.55; H, 9.61. Alkene 14b: Colourless oil. IR (thin film): 3069 cm^-1. ¹H NMR (CDCl₃, 270 MHz): d = 7.52 (m, 2 H), 7.35 (m, 3 H), 5.95 (d, 1 H, J = 17.1, 10.2 Hz), 4.86 (d, 1 H, J = 10.2 Hz), 4.80 (d, 1 H, J = 17.1 Hz) 1.24-0.20 (m, 5 H), 0.30 (s, 3 H), 0.29 (s, 3 H), 0.03 (s, 9 H). ¹³C NMR (CDCl₃, 68 MHz): δ = 144.7, 140.1, 134.3, 129.5, 128.4, 112.8, 22.7, 19.2, 18.7, 18.4, 0.0, -2.1, -2.3. HRMS (CI) calcd for C₁₇H₂₉Si₂:
[M + 1]⁺ 289.1808. Found: [M + 1] ⁺, 289.1807.

16a The diene isomers were assigned by the NMR method of Chan et. al.: Chan TH. Mychajlowskij W. Amouroux R. Tetrahedron Lett.  1977,  19:  1605 

16b

Skipped diene (E)-15 shows a ¹³C resonance for the TMS group at -1.20 ppm. Skipped diene (Z)-15 displays its equivalent resonance at 0.41 ppm.