Download PDF
Synlett 2006(10): 1485-1490  
DOI: 10.1055/s-2006-941582
LETTER
© Georg Thieme Verlag Stuttgart · New York

Radicals from Aldehydes: A Convergent Access to Dienes and δ-Lactones

Sharanjeet K. Bagal, Lucie Tournier, Samir Z. Zard*
Laboratoire de Synthèse Organique associé au CNRS, Ecole Polytechnique, 91128 Palaiseau, France
Fax: +33(1)69333851; e-Mail: zard@poly.polytechnique.fr;
Further Information

Publication History

Received 30 January 2006
Publication Date:
12 June 2006 (online)

    Permissions and Reprints All articles of this category

Abstract

A convenient method for the generation of O,S-acetal xanthates from aldehydes has been developed. The corresponding nucleophilic radicals undergo facile addition to unactivated olefins and the resulting adducts can be further elaborated to generate dienes and unsaturated δ-lactones.

Key words

aldehydes - xanthates - radical reactions - lactones - dienes

6

The reaction yields reported are for preliminary studies and hence are unoptimised.

7

Yields based upon recovered starting material are given in parentheses.

15

General Procedure for Preparation of Xanthates 4a-e.
To a flask containing freshly fused catalytic ZnCl2 (ca. 5 mg) under argon was added acetyl chloride (2.4 mmol) and the mixture cooled to -5 °C to -10 °C. The aldehyde (1 mmol) was then added dropwise and the resulting reaction mixture stirred at r.t. for 1 h. The mixture was then concentrated under reduced pressure to afford crude chloride 3. To a solution of crude chloride 3 in EtOH or acetone (1 M) at 0 °C under argon was added portionwise potassium O-ethyl xanthate (1.5 mmol) and the resulting mixture stirred at r.t. for 18 h overnight. The mixture was then concentrated under reduced pressure and diluted with H2O and Et2O. The aqueous layer was extracted with Et2O and the organic layers were combined, washed with H2O, brine, dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash chromatography (silica gel) gave xanthates 4 as yellow oils. Note that in some cases, using 0.5 equiv of acetyl chloride gave higher product yields.
Data for (±)-Xanthate 4e.
R f = 0.2 [PE (40-60)-Et2O, 97:3]. IR (film): νmax = 2929 (s), 2855 (s), 1753 (s), 1368 (s), 1221 (s), 1111 (s), 1051 (s) cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.93-1.30 (5 H, m), 1.40 (3 H, t, J = 7.0 Hz), 1.61-1.90 (6 H, m), 2.07 (3 H, s), 4.55-4.70 (2 H, m), 6.57 (1 H, d, J = 5.5 Hz). 13C NMR (100.6 MHz, CDCl3): δ = 13.7 (CH3), 20.9 (CH3), 25.8 (2 CH2), 26.0 (CH2), 28.5 (CH2), 28.9 (CH2), 42.0 (CH), 70.1 (CH2), 84.7 (CH), 169.3 (C), 210.7 (C). MS (CI): m/z (%) = 294 (10) [MNH4 +], 277 (10) [MH+], 217 (100). HRMS: m/z calcd for C12H20O3S2: 276.0854. Found: 276.0845 [M+].

16

General Procedure for Radical Addition. A solution of xanthate (1 mmol) and the desired olefin (2 mmol) in 1,2-dichloroethane (DCE, 2 mL) was refluxed for 15 min under nitrogen. Lauroyl peroxide (DLP, 5% mol) was then added to the refluxing solution, followed by additional portions (5% mol) every 1.5 h until the xanthate was completely consumed. The mixture was then cooled to r.t., concentrated under reduced pressure and purified by flash chromatography (silica gel). A small layer of basic alumina was placed on top of the silica to remove any lauric acid present. Data for (±)-Xanthate Adduct 5eD.
R f = 0.2 [PE (40-60)-Et2O, 4:1]. IR (film): νmax = 2929 (s), 2855 (s), 2251 (w), 1735 (s), 1446 (s), 1234 (s), 1051 (s), 733 (s) cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.93-1.28 (10 H, m), 1.36-1.45 (6 H, m), 1.45-1.59 (2 H, m), 1.59-1.80 (10 H, m), 1.97-2.08 (4 H, m), 2.05 (3 H, s), 2.09 (3 H, s), 2.80-3.05 (4 H, m), 3.78-3.87 (1 H, m), 3.88-3.97 (1 H, m), 4.59-4.68 (4 H, m), 4.78-4.86 (1 H, m), 4.88-4.97 (1 H, m). 13C NMR (100.6MHz, CDCl3): δ = 13.8 (2 CH3), 21.1 (2 CH3), 22.6 (CH2), 24.4 (CH2), 25.9 (2 CH2), 26.0 (2 CH2), 26.2 (CH2), 26.3 (CH2), 27.9 (CH2), 28.2 (CH2), 28.5 (CH2), 28.9 (CH2), 33.8 (CH2), 34.3 (CH2), 41.5 (CH), 41.9 (CH), 43.1 (CH), 43.9 (CH), 70.5 (CH2), 70.6 (CH2), 74.4 (2 CH), 116.9 (C), 117.1 (C), 170.5 (C), 171.0 (C), 212.0 (C), 212.3 (C). MS (EI): m/z (%) = 343 (40) [M+], 283 (100). HRMS: m/z calcd for C16H25O3NS2: 343.1276. Found: 343.1287 [M+].

17

Procedure for Preparation of Xanthate 12. To a flask containing levulinic acid (10, 8 g, 69 mmol, 1 equiv) under nitrogen at 0 °C was added dropwise freshly distilled SOCl2 (6 mL, 83 mmol, 1.2 equiv) and the resulting mixture stirred for 1 h. The reaction mixture was then allowed to warm to r.t. and concentrated in vacuo to afford crude chloride 11. To a solution of crude chloride 11 in acetone (70 mL) at 0 °C under nitrogen was added portionwise potassium O-ethyl xanthate (13.3 g, 83 mmol, 1.2 equiv) and the resulting mixture stirred at r.t. for 18 h overnight. The mixture was then concentrated under reduced pressure and diluted with H2O and Et2O. The aqueous layer was extracted with Et2O and the organic layers were combined, washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash chromatography [PE (40-60)-EtOAc, 9:1] gave xanthate 12 as a yellow oil (13.7 g, 90%, 2 steps).
Data for (±)-Xanthate 12.
R f = 0.1 [PE (40-60)-EtOAc, 9:1]. IR (film): νmax = 2981 (s), 2933 (s), 1791 (s), 1241 (s), 1128 (s), 1040 (s), 896 (s) cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.50 (3 H, t, J = 7.0 Hz), 1.96 (3 H, s), 2.35-2.42 (1 H, m), 2.63-2.91 (3 H, m), 4.67-4.77 (2 H, m). 13C NMR (100.6 MHz, CDCl3): δ = 13.7 (CH3), 28.6 (CH3), 28.8 (CH2), 35.2 (CH2), 70.2 (CH2), 94.4 (C), 175.1 (C), 209.4 (C). MS (CI): m/z (%) = 238 (100) [MNH4 +], 221 (48) [MH+]. HRMS: m/z calcd for C8H12O3S2: 220.0228. Found: 220.0234 [M+].

18

Data for (±)-Xanthate Adduct 13H.
R f = 0.15 [PE (40-60)-Et2O-CH2Cl2, 7.5:1.5:1]. IR (film): νmax = 2829 (s), 2856 (s), 1774 (s), 1737 (s), 1444 (s), 1364 (s), 1216 (s), 1052 (s), 734 (s) cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.23-1.50 (17 H, m), 1.46 (6 H, t, J = 7.0 Hz), 1.47 (3 H, s), 1.53 (3 H, s), 1.57-1.97 (9 H, m), 2.00-2.22 (8 H, m), 2.33 (4 H, t, J = 7.5 Hz), 2.36-2.46 (2 H, m), 2.54-2.75 (4 H, m), 3.69 (6 H, s), 3.78-3.96 (2 H, m), 4.67 (4 H, q, J = 7.0 Hz). 13C NMR (100.6 MHz, CDCl3): δ = 13.8 (2 CH3), 24.8 (CH3), 24.9 (2 CH2), 27.0 (CH3), 27.0 (CH2), 28.6 (CH2), 29.0 (2 CH2), 29.1 (3 CH2), 29.2 (4 CH2), 29.3 (CH2), 32.5 (CH2), 34.0 (2 CH2), 34.7 (2 CH2), 35.9 (CH2), 44.3 (CH2), 45.1 (CH2), 46.7 (CH), 47.3 (CH), 51.3 (2 CH3), 69.9 (CH2), 70.0 (CH2), 85.9 (C), 86.1 (C), 174.2 (2 C), 176.2 (C), 176.3 (C), 214.0 (C), 214.1 (C). MS (CI): m/z (%) = 436 (100) [MNH4 +], 419 (44) [MH+]. HRMS: m/z calcd for C20H34O5S2: 418.1848. Found: 418.1844 [M+].

19

General Procedure for Diene Formation. To a solution of xanthate (1 mmol) in CH2Cl2 or MeCN (0.1 M) at r.t. under nitrogen was added DBU (2.2 mmol) dropwise and the resulting mixture stirred for 18 h overnight. The mixture was then concentrated under reduced pressure and diluted with H2O and Et2O. The aqueous layer was extracted with Et2O and the organic layers were combined, washed several times with sat. aq NH4Cl and then brine, dried (Na2SO4), filtered and concentrated in vacuo. Purifi-cation was performed by flash chromatography (silica gel). Data for (±)-(2 E ,4 E )- and (±)-(2 Z ,4 E )-5-Cyclohexyl-penta-2,4-dienenitrile ( 17).
Purification by flash chromatography [PE(40-60)-CH2Cl2, 7:3) gave diene 17 as a pale yellow oil (81%) and as a mixture of 2 diastereomers in a 2E,4E/2Z,4E ratio of 1.3:1. Only traces of the 2E,4Z and 2Z,4Z diastereomers could be detected in the NMR spectra.
R f = 0.5 and 0.35 [PE (40-60)-CH2Cl2, 1:1]. IR (film):
νmax = 3039 (m), 2927 (s), 2856 (s), 2214 (s), 1637 (s), 1595 (s), 994 (s), 742 (s) cm-1. MS (CI): m/z (%) = 179 (100) [MNH4 +], 162 (1) [MH+]. HRMS: m/z calcd for C11H15N: 161.1205. Found: 161.1207 [M+] NMR Data for (±)-(2 E ,4 E )-Isomer.
1H NMR (400 MHz, CDCl3): δ = 1.08-1.43 (5 H, m), 1.59-1.86 (5 H, m), 2.07-2.26 (1 H, m), 5.28 (1 H, d, J = 16.0 Hz), 6.11-6.16 (2 H, m), 7.01 (1 H, dd, J = 16.0, 10.0 Hz).
13C NMR (100.6 MHz, CDCl3): δ = 24.3 (CH2), 24.4
(2 CH2), 30.6 (2 CH2), 41.2 (CH), 96.5 (CH), 115.4 (CN, very weak), 125.5 (CH), 151.4 (CH), 151.6 (CH). NMR Data for (±)-(2 Z ,4 E )-Isomer.
1H NMR (400 MHz, CDCl3): δ = 1.08-1.43 (5 H, m), 1.59-1.86 (5 H, m), 2.07-2.26 (1 H, m), 5.14 (1 H, d, J = 11.0 Hz), 6.11-6.20 (1 H, m), 6.55 (1 H, dd, J = 15.0, 11.0 Hz), 6.82 (1 H, t, J = 11.0 Hz). 13C NMR (100.6 MHz, CDCl3): δ = 24.3 (CH2), 24.5 (2 CH2), 30.7 (2 CH2), 41.1 (CH), 94.8 (CH), 117.1 (CN, very weak), 124.4 (CH), 150.2 (CH), 151.3 (CH).

20

General Procedure for Lactone Formation. To a solution of 5dD, 5cE or 5cF (100 mg) in EtOH (10 mL) at r.t. under nitrogen was added concd HCl (1 mL) and the resulting mixture refluxed (EtOH) for 72 h. The mixture was then cooled to r.t., concentrated under reduced pressure and diluted with Et2O (50 mL). The ethereal phase was washed with sat. aq K2CO3, dried (MgSO4), filtered and concen-trated in vacuo. Purification by flash chromatography (silica gel) gave lactones 19, 20, 21 as yellow oils. Data for (±)-6-Isobutyl-3-methyl-5,6-dihydro-pyran-2-one ( 21).
R f = 0.2 [PE (40-60)-EtOAc, 9:1]. IR (film): νmax = 2959 (s), 2929 (s), 1726 (s), 1368 (s), 1113 (s), 786 (s) cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.88 (6 H, d, J = 6.5 Hz), 1.26-1.37 (1 H, m), 1.65-1.75 (1 H, m), 1.77-1.92 (1 H, m), 1.86 (3 H, s), 2.17-2.28 (2 H, m), 4.34-4.46 (1 H, m), 6.49-6.58 (1 H, m). 13C NMR (100.6 MHz, CDCl3): δ = 17.0 (CH3), 22.1 (CH), 23.0 (CH3), 23.9 (CH3), 30.3 (CH2), 44.0 (CH2), 76.4 (CH), 128.4 (C), 139.0 (CH), 166.2 (C). MS (CI): m/z (%) = 186 (100) [MNH4 +], 169 (100) [MH+].