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Synlett 2008(11): 1618-1622  
DOI: 10.1055/s-2008-1077825
LETTER
© Georg Thieme Verlag Stuttgart · New York

Conjugate Allylation of Cyclic α,β-Unsaturated Esters

Christine Hofmann, Angelika Baro, Sabine Laschat*
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: +49(711)68564285; e-Mail: sabine.laschat@oc.uni-stuttgart.de;
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Publication History

Received 10 January 2008
Publication Date:
11 June 2008 (online)

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Abstract

The conjugate allylation of a homologous series of α,β-unsaturated cyclic esters 8-10 by addition of diallylcuprate (method A), fluoride ion catalyzed addition of trimethylallylsilane (method B), and aluminium tris(2,6-diphenylphenoxide) (ATPH)-mediated addition of allyllithium (method C) was investigated. Method A was not selective in all cases. For methods B and C an influence of ester moiety and ring size on the regioselectivity was observed. Meth­yl cyclopentenoate 8c gave mainly the 1,2/1,2-product regardless the allylation method while tert-butyl and benzyl ester moieties favored the 1,4-products. For larger rings 9, 10 and the anellated system 19 methods B and C behave complementary depending on the ester function: Method B gave best results of 1,4-addition products for benzyl esters while method C worked better for tert-butyl esters.

Key words

conjugate allylation - cycloalkenecarboxylates - regio­selectivity - pentalene

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The initial 1,2-adduct, an enone, is capable of further 1,2-addition, giving the tertiary alcohol.5

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General Procedures for the Allylation According Method B
In a Schlenk flask 4 Å MS (2.00 g) and TBAF (1.31 g, 0.50 mmol) were dried under high vacuum for 30 min. Under N2 atmosphere DMF (15 mL) was added, the mixture stirred for 30 min, transferred via cannula in a Schlenk flask with 4 Å MS (2.00 g), and stirred for a further 30 min. A solution of the respective ester (1 mmol) in DMF (5 mL) was added followed by HMPA (1.04 mL, 1.07 g, 6.00 mmol) and a solution of trimethylallylsilane (0.95 mL, 685 mg, 6.00 mmol) in DMF (5 mL) at 0 °C. After stirring at 0 °C for 10 min, 1 N HCl in MeOH (5 mL) and H2O (40 mL) were successively added, and the aqueous layer was extracted with EtOAc (2 × 100 mL). The combined organic layers were dried (MgSO4), concentrated under vacuum, and the crude product was chromatographed on SiO2 with hexanes-EtOAc.
Benzyl 2-Allylcyclohexanecarboxylate (15b)
R f = 0.37 (hexanes-EtOAc, 10:1). 1H NMR (500 MHz, CDCl3): δ = 0.89-0.98 (m, 1.5 H, CH2), 1.14-2.03 (m, 13.5 H, Ha-1′, Ha*-1′, H-2, H*-2, H-3, H*-3, H-4, H*-4, H-5, H*-5, H-6, H*-6), 2.06-2.16 (m, 2.5 H, Hb-1′, Hb*-1′, H-1), 2.65 (dt, J = 8.1, 4.1 Hz, 0.5 H, H*-1) 4.90-4.98 (m, 2 H, H-3′), 5.06-5.15 (m, 3 H, ArCH 2, ArCH 2*), 5.65-5.76 (m, 1.5 H, H-2′, H*-2′), 7.29-7.38 (m, 7.5 H, Ar, Ar*) ppm. 13C NMR (125 MHz, CDCl3): δ = 22.6*, 23.8*, 25.4, 25.4*, 25.6, 28.0*, 30.1, 30.8 (C-3, C-4, C-5, C-6), 37.2*, 38.7 (C-2), 34.9*, 39.3 (C-1′), 44.8*, 49.4 (C-1), 65.8*, 65.9 (ArCH2), 115.9*, 116.3 (C-3′), 128.09*, 128.1, 128.1*, 128.2, 128.5, 128.5* (Ar), 136.0, 136.1* (Ar), 136.3, 137.3* (C-2′), 174.6*, 175.9 (CO) ppm. (* denotes minor diastereomer). FT-IR (ATR): 2319 (s), 2856 (s), 2360 (s), 1732 (vs), 1259 (s), 1164 (s), 749 (vs) cm-1. MS (ESI): m/z (%) = 241 (15) [M+ - O], 223 (36), 131 (28), 117 (20), 91 (71) [C7H7 +]. HRMS (ESI): m/z calcd for C17H22NaO2 [M + Na]: 281.1512; found: 281.1503.
Benzyl (3a′ R ,4′ R ,5′ R ,6a′ S )-4′-Allylhexahydro-2′ H -spiro[1,3-dioxolane-2,1′-pentalene]-5′-carboxylate (4) R f = 0.58 (hexanes-EtOAc, 6:1); [α]D 20 +23 (c 1.00, CH2Cl2). 1H NMR (500 MHz, CDCl3): δ = 1.45 (ddd, J = 12.6, 7.3, 2.7 Hz, 1 H, Ha-2′), 1.66-1.71 (m, 1 H, Ha-3′), 1.74-1.87 (m, 2 H, Ha-6, Hb-2′), 1.89-1.98 (m, 2 H, H-4′, Hb-3′), 2.04 (ddd, J = 12.9, 8.6, 6.3 Hz, 1 H, Hb-6′), 2.10-2.27 (m, 3 H, H-1′′, H-3a′), 2.35-2.44 (m, 2 H, H-5′, H-6a′), 3.79-3.98 (m, 4 H, OCH2CH2O), 5.09 (d, J = 5.3 Hz, 2 H, CH 2Ph), 4.92 (ddt, J = 10.0, 2.1, 1.0 Hz, 1 H, Ha-3′′), 4.98 (ddt, J = 17.1, 2.1, 1.4 Hz, 1 H, Hb-3′′), 5.73 (ddt, J = 17.1, 10.0, 7.2 Hz, 1 H, H-2′′), 7.28-7.38 (m, 5 H, Ph) ppm. 13C NMR (125 MHz, CDCl3): δ = 27.8 (C-2′), 32.9, 33.1 (C-6′, C-3′), 37.8 (C-1′′), 46.7 (C-3a′), 48.9, 51.1 (C-5′, C-6a′), 50.4 (C-4′), 63.8, 64.8 (OCH2CH2O), 66.1 (CH2Ph), 116.3 (C-3′′), 118.2 (C-1′), 127.6, 128.1, 128.2 (Ph), 136.1 (CH2 Ph), 136.4 (C-2′′), 174.6 (CO) ppm. FT-IR (ATR): 2946 (w), 2880 (w), 2362 (w), 2342 (w), 1455 (w), 1338 (w), 1152 (s), 1023 (s), 697 (s) cm-1. GC-MS (EI): m/z (%) = 342 (2) [M+], 301 (8) [M+ - C3H5], 251 (6) [M+ - C7H7], 223 (6), 207 (14) [M+ - CO2CH2C6H5], 107 (10) [C7H7O+], 99 (100), 91 (30) [C7H7 +]. HRMS (ESI): m/z calcd for C21H26O4Νa [M + Na]: 365.1723; found: 365.1722.

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General Procedures for the Allylation According Method C Trimethyl aluminium (1.10 mL, 1 M in hexane, 1.10 mmol) was slowly added to a solution of 2,6-diphenylphenol (813 mg, 3.30 mmol) in toluene (6 mL) in a Schlenk flask, and the mixture stirred at r.t. for 30 min. Then a solution of the respective ester (1.00 mmol) in toluene (3 mL) was added. After 5 min, the mixture was cooled to -78 °C and stirred for 1 h. In a further flask n-BuLi (0.88 mL, 1.6 M in hexane, 1.40 mmol) was slowly added to a solution of allyltributyltin (0.43 mL, 463 mg, 1.40 mmol) in THF (4 mL) at -78 °C, and after stirring for 45 min, this allyllithium solution was transferred via cannula to the solution of the ATPH complex, and the reaction mixture stirred at -78 °C for a further 45 min. The reaction was quenched with MeOH (10 mL) and 1 N HCl (5 mL), and the aqueous layer extracted with Et2O (50 mL). The organic layer was separated, dried (MgSO4), concentrated, and the crude product chromatographed on SiO2 with hexanes-EtOAc (50:1).
tert -Butyl 2-Allylcyclopentanecarboxylate (11a)
R f = 0.74 (hexanes-EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 1.21-1.27 (m, 1 H, Ha-3), 1.44 [s, 9 H, C(CH3)3], 1.45 [s, 4.5 H, C(CH3)3*], 1.49-1.54 (m, 1 H, Ha*-4, Ha*-3), 1.58-1.69 (m, 2 H, H-4), 1.70-2.00 (m, 5.5 H, Hb-3, H-5, Ha*-1′, Hb*-3, Hb*-4, H*-5), 2.02-2.09 (m, 1 H, Ha-1′), 2.09-2.18 (m, 1.5 H, H-2, H*-2), 2.19-2.29 (m, 2.5 H, H-1, Hb-1′, Hb*-1′), 2.78 (ddd, J = 7.8, 7.8, 5.6 Hz, 0.5 H, H*-1), 4.95-5.05 (m, 3 H, H-3′, H*-3′), 5.75-5.86 (m, 1.5 H, H-2′, H*-2′) ppm. 13C NMR (75 MHz, CDCl3): δ = 23.5*, 24.6 (C-4), 28.1, 28.2* [C(CH3)3], 28.3*, 30.2 (C-5), 30.7*, 32.1 (C-3), 35.4*, 39.3 (C-1′), 43.3*, 43.7 (C-2), 48.4*, 50.7 (C-1), 79.8, 80.0* [C(CH3)3], 115.3*, 115.6 (C-3′), 137.3, 137.9* (C-2′), 174.8*, 175.8 (CO) ppm. (* denotes minor diastereomer). FT-IR (ATR): 1723 (s), 1365 (s), 1256 (s), 1144 (vs) cm-1. GC-MS (EI): m/z (%) = 210 (1) [M+], 154 (60) [M+ - C(CH3)], 137 (28) [M+ - OCMe3], 109 (56)
[M+ - CO2CMe3], 67 (32), 57 (100) [C4H9 +]. HRMS (ESI): m/z calcd for C13H22NaO2 [M + Na]: 233.1512; found: 233.1510.
tert -Butyl 2-Allylcycloheptanecarboxylate (16a)
R f = 0.68 (hexanes-EtOAc, 10:1). 1H NMR (500 MHz, CDCl3): δ = 1.25-1.34 (m, 1 H, Ha-3), 1.37-1.51 (m, 3 H, Ha-4, CH2), 1.46 [s, 9 H, C(CH3)3], 1.53-1.75 (m, 6 H, Hb-3, Hb-4, H-7, CH2), 1.89-1.99 (m, 2 H, Ha-1′, H-2), 2.00-2.22 (m, 2 H, H-1, Hb-1′), 4.96-5.04 (m, 2 H, H-3′), 5.72-5.81 (m, 1 H, H-2′) ppm. 13C NMR (125 MHz, CDCl3): δ = 26.1, 26.2, 26.3*, 26.5* (C-5, C-6), 28.1, 28.2* [C(CH3)3], 28.3*, 29.3 (C-4), 28.6*, 30.3 (C-7), 30.7, 30.7* (C-3), 37.7*, 40.6 (C-1′), 40.2*, 40.5 (C-2), 48.2*, 51.8 (C-1), 79.7, 79.8* [C(CH3)3], 115.7*, 116.3 (C-3′), 137.1, 138.0* (C-2′), 175.1*, 176.4 (CO) ppm. FT-IR (ATR): 2923 (s), 1723 (vs), 1366 (s), 1142 (vs), 910 (s) cm-1. GC-MS (EI): m/z (%) = 238 (4) [M+], 181 (100) [M+ - CMe3], 165 (24) [M+ - OCMe3], 140 (14), 136 (16) [M+ - CO2CMe3], 122 (10), 109 (20), 95 (56), 81 (24), 67 (12), 57 (90) [C4H9 +], 41 (24) [C3H5 +], 29 (10). HRMS (ESI): m/z calcd for C15H27O2 [M + H]: 239.2006; found: 239.2017.
1-{(3a′ R ,6a′ S )-3′,3a′6′,6a′-tetrahydro-2′ H -spiro[1,3-dioxolane-2,1′-pentalen]-5′-yl}but-3-en-1-one (20)
R f = 0.38 (hexanes-EtOAc, 6:1). 1H NMR (500 MHz, CDCl3): δ = 1.54-1.72 (m, 3 H, Ha-3′, H-2), 1.98 (dddd, J = 12.1, 10.7, 9.1, 6.5 Hz, 1 H, Hb-3′), 2.59-2.68 (m, 2 H, Ha-6′, H-6a′), 2.76 (dddd, J = 12.6, 2.9, 1.9, 1.9 Hz, 1 H, Hb-6′), 3.44 (dddd, J = 6.7, 2.2, 1.4, 1.4 Hz, 2 H, CH 2CH=CH2), 3.44-3.51 (m, 1 H, H-3a′), 3.85-3.95 (m, 4 H, OCH2CH2O), 5.09-5.20 (m, 2 H, CH2CH=CH 2), 5.96 (ddt, J = 17.2, 10.3, 6.7 Hz, 1 H, CH2CH=CH2), 6.52 (dddd, J = 3.7, 1.9, 1.9, 0.9 Hz, 1 H, H-4′) ppm. 13C NMR (125 MHz, CDCl3): δ = 27.7 (C-3′), 32.9 (C-6′), 33.4 (C-2′), 44.2 (CH2CH=CH2), 46.3 (C-6a′), 49.6 (C-3a′), 63.9, 64.9 (OCH2CH2O), 118.2 (CH2 CH=CH2), 127.7 (C-1′), 131.4 (CH=), 143.6 (C-5′), 145.3 (C-4′), 197.6 (CO) ppm. FT-IR (ATR): 2952 (s), 2875 (s), 1665 (vs), 1617 (s), 1202 (s), 1105 (vs), 1028 (vs), 993 (s), 914 (s), 735 (s) cm-1. MS (ESI): m/z (%) = 257 (100)
[M + Na], 235 (6) [M + H], 211 (8), 193 (16) [M+ - C3H5], 173 (8), 149 (76) [C11H17 +], 131 (8), 121 (8) [C9H13 +], 105 (16), 99 (8). HRMS (ESI): m/z calcd for C14H19O3 [M + H]: 235.1329; found: 235.1320.

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tert -Butyl 2-(2-Hydroxyethyl)cyclopentane-carboxylate (13)
Ozone was passed through a solution of 11a (70 mg, 0.33 mmol) in MeOH-CH2Cl2-pyridine (4:4:1) at -78 °C. Then N2 was passed for 1 min, NaBH4 (33 mg, 0.84 mmol) was added, and the reaction mixture warmed to 0 °C and stirred for 3 h. After quenching with a sat. NH4Cl soln (5 mL), the reaction mixture was extracted with EtOAc (20 mL). The combined organic layers were washed with brine (10 mL), dried (MgSO4), and concentrated under vacuum. The residue was chromatographed on SiO2 with hexanes-EtOAc (3:1, R f = 0.34) to give 13 as a colorless oil (52 mg, 74%, dr 67:33). 1H NMR (500 MHz, CDCl3): δ = 1.18-1.28 (m, 1 H, Ha-3), 1.45 [s, 13.5 H, C(CH3)3, C(CH3)3*], 1.52-1.96 (m, 11 H, H-1′, H*-1′, Hb-3, H*-3, H-4, H*-4, H-5, H*-5), 2.11-2.25 (m, 1.5 H, H-2, H-2*), 2.29 (dt, J = 8.8, 7.8 Hz, 1 H, H-1), 2.76 (dt, J = 7.8, 4.6 Hz, 0.5 H, H*-1), 3.60-3.76 (m, 3 H, H-2′, H*-2′) ppm. 13C NMR (125 MHz, CDCl3): δ = 23.6*, 24.8 (C-4), 28.1, 28.2* [C(CH3)3], 28.5*, 30.6 (C-5), 31.2*, 33.3 (C-3), 34.1*, 38.4 (C-1′), 40.2, 40.6* (C-2), 48.4, 50.9 (C-1), 61.6, 62.2 (C-2′), 80.2*, 80.3 [C(CH3)3], 175.1*, 175.5 (CO) ppm. FT-IR (ATR): 2935 (s), 2871 (s), 1722 (vs), 1366 (s), 1145 (vs), 1051 (s), 847 (s) cm-1. GC-MS (EI): m/z (%) = 184 (1), 158 (18) [M+ - C(CH3)], 141 (44) [M+ - OCMe3], 129 (12), 112 (8) [M+ - CO2CMe3], 95 (50), 67 (16), 57 (100) [C4H9 +], 41 (18) [C3H5 +]. HRMS (ESI): m/z calcd for C12H22NaO3 [M + Na]: 237.1461; found: 237.1453.

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Compound 19 was obtained from enantiomerically pure pentalene-1,4-dione monoacetal1b via α-acylation, reduction of the carbonyl group, and subsequent dehydration following the method by Burgess.24