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Synlett 2006(10): 1523-1526  
DOI: 10.1055/s-2006-941598
LETTER
© Georg Thieme Verlag Stuttgart · New York

Lactones, Part 28: [1] A New Approach for the Synthesis of α-Methylene Lactones from Alkenes

Antoni Szumny*, Czeslaw Wawrzenczyk
Department of Chemistry, Agricultural University, Norwida 25, 50-375 Wroclaw, Poland
e-Mail: antjasz@o2.pl;
Further Information

Publication History

Received 23 January 2006
Publication Date:
12 June 2006 (online)

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Abstract

A facile two-step procedure for synthesis of α-methylene lactones from alkenes and cycloalkenes is presented. Reactions ­carried out on some monoterpene alkenes afforded corresponding lactones in enantiomerically pure forms.

Key words

α-methylene lactone - CAN - Meldrum’s acid

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General Procedure.
CAN (20 mmol) was slowly added to a cooled (ice bath) and vigorously stirred solution of alkene (10 mmol) and Meldrum’s acid (or ethyl acetoacetate for compound 10) (10 mmol) in 50 mL MeCN. The reaction was complete when the orange color of the mixture turned to pale-yellow (usually after 1 h). Then the solvent was evaporated (below 50 °C, because of possible decarboxylation reaction). Then, H2O (100 mL) was added to the residue and the product was extracted with EtOAc (3 × 40 mL). Combined ethereal solutions were washed with brine. The purification of crude product via NaHCO3-HCl procedure significantly decreased the yield of this reaction. So in the next step crude α-car-boxylactone was stirred overnight with 3 mL of stock solution containing Et2NH (3 mL), 30% formaldehyde (6 mL), NaOAc (0.2 g) and AcOH (8 mL). The reaction mixture was acidified with 10% HCl (50 mL) and extracted with Et2O. Crude product was purified by column chromatography (eluent hexane-Et2O, starting from 20:1 and next 2:1).The physical and spectral data of compounds obtained are presented below.

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Analytical Data for Compounds Obtained.
Compound 1a: n D 20 1.4605. 1H NMR (300 MHz, CDCl3): δ = 6.19 (1 H, t, J = 2.8 Hz, =CH2), 5.57 (1 H, t, J = 2.4 Hz, =CH2), 2.72 (1 H, dt, J = 16.8, 2.8 Hz, CH2 in lactone), 2.68 (1 H, dt, J = 16.8, 2.4 Hz, CH2 in lactone), 1.71 and 1.65 [2 H, 2 d, J = 14.8 Hz ,(CH3)3CCH 2, AB system], 1.44 [3 H, s, (CH3)CO], 1.00 [9 H, s, (CH 3)3CCH2]. IR (film): 1778 (s), 1675 (m), 1290 (m), 1108 (m) cm-1. MS (EI): m/z (%) = 183 [M + H](7), 167 (1), 126 (4), 111 (100), 83 (18), 68 (5).
Compound 2a: mp 86 °C. 1H NMR (300 MHz, CDCl3): δ = 6.21 (1 H, t, J = 2.9 Hz, =CH2), 5.61 (1 H, t, J = 2.4 Hz, =CH2), 4.50 [1 H, tt, J = 7.6, 5.6 Hz, >CH(O)], 3.01 (1 H, ddt, J = 17.0, 7.6, 2.5 Hz, CH2 in lactone), 2.56 (1 H, ddt, J = 17.0, 5.9, 2.9 Hz, CH2 in lactone), 1.52-1.76 [2 H, m, CH3(CH2)10CH 2], 1.16-1.44 [20 H, m, CH3(CH 2)10CH2], 0.86 [3 H, t, J = 6.9 Hz, CH 3(CH2)10CH2]. IR (KBr): 1776 (s), 1676 (w), 1284 (m), 1124 (m), 944 (m) cm-1. MS (EI): m/z (%) = 267 (72) [M + H], 249 (13), 227 (13), 221 (25), 171 (23), 123 (34), 109 (52), 97 (100), 83 (31), 69 (69).
Compound 3a: n D 20 1.4885. 1H NMR (300 MHz, CDCl3): δ = 6.22 (1 H, m, >C=CH2), 5.85 (1 H, dd, J = 17.2, 11.0 Hz, CH2=CH), 5.60 (1 H, m, =CH2), 5.22 (1 H, d, J = 17.2 Hz, CH 2=CH), 5.17 (1 H, d, J = 11.0 Hz, CH 2=CH), 5.06 [1 H, t, J = 5.6 Hz, (CH3)2C=CH], 2.82 (2 H, s, CH2 in lactone), 2.06 (2 H, m, =CHCH 2CH2), 1.76 (2 H, t, J = 8.2 Hz, =CHCH2CH 2), 1.67 [3 H, s, =C(CH3)2], 1.59 [3 H, s, =C(CH3)2]. IR (film,): 1766 (s), 1665 (w), 1276 (m), 1072 (w), 934 (w) cm-1. MS (EI): m/z (%) = 207 [M + H] (59), 189 (54), 173 (8), 161 (100), 145 (35), 133 (18), 121 (80), 105 (29), 93 (48), 67 (4).
Compound 4a: n D 20 1.4962. 1H NMR (300 MHz, CDCl3): δ = 6.20 (1 H, d, J = 3.0 Hz, =CH2), 5.44 (1 H, d, J = 2.7 Hz, =CH2), 2.73 (1 H, m, >CHCH2), 1.71-1.25 [m, 8 H, (CH2)4 in cyclohexyl], 1.46 (3 H, s, CH3). IR (film): 1776 (s), 1676 (m), 1168 (m), 936 (m) cm-1. MS (EI): m/z = 167 (100) [M + H], 151 (14), 138 (10), 123 (61), 108 (9), 95 (18), 79 (8), 67 (10).
Compound 5a: n D 20 1.5085. 1H NMR (600 MHz, CDCl3): δ = 6.20 (1 H, t, J = 2.8 Hz, =CH2), 5.58 (1 H, m, =CH2), 5.35 (1 H, m, >C=CH), 2.87 (dt, J = 17.1, 2.8 Hz, CH2 in lactone, diastereomer A), 2.86 (dt, J = 17.0, 3.1 Hz, CH2 in lactone, diastereomer B), 2.57 (1 H, dt, J = 17.0, 2.8 Hz, CH2 in lactone, diastereomer B), 2.56 (1 H, dt, J = 17.1, 2.4 Hz, CH2 in lactone, diastereomer A), 1.70-2.12 (7 H, m, CH2 and >CH in cyclohexyl), 1.61 [3 H, s, =C(CH3)], 1.35 and 1.34 [3 H, 2 s, >C(O)CH3 for both diastereomers]. IR (film): 1768 (s), 1668 (w), 1296 (s), 1060 (m) cm-1. MS (EI): m/z (%) = 207 (40) [M + H], 189 (9), 161 (15), 121 (100), 111 (37), 93 (27), 93 (27), 83 (19).
Compound 6a: [α]D 20 -46 (c 1.85 CHCl3); n D 20 1.5321. 1H NMR (300 MHz, CDCl3): δ = 6.25 (1 H, d, J = 2.7 Hz, =CH2), 5.54 (1 H, d, J = 2.3 Hz, =CH2), 2.69 (1 H, m, CH< in lactone), 2.07 (1 H, dd, J = 14.6, 6.8 Hz, >CHCH 2), 1.88 (1 H, dd, J = 14.6, 5.1 Hz, >CHCH 2), 1.30 [3 H, s, (CH3)CO<], 1.10 (1 H, m, >CHCH 2CH<), 0.93 and 0.94 [6 H, two s, (CH3)2C<], 0.81 (1 H, m, >CHCH 2CH<), 0.44-0.56 (2 H, m, cyclopropyl). IR (film): 1768 (s), 1668 (w), 1296 (s), 1060 (m) cm-1. MS (EI): m/z (%) = 206 (53) [M+], 191 (23), 177 (13), 163 (53), 145 (25), 121 (22), 110 (98), 96 (73), 82 (100), 67 (30).
Compound 7a: mp 73-74 °C; 1H NMR (600 MHz, CDCl3): δ = 6.13 (1 H, t, J = 2.8 Hz, =CH2), 5.57 (1 H, t, J = 2.7 Hz, =CH2), 2.91 (1 H, dt, J = 17.0, 2.7 Hz, CH2 in lactone), 2.80 (1 H, dt, J = 17.0, 2.8 Hz, CH2 in lactone), 2.15 (1 H, dd, J = 6.4, 1.1 Hz, H-1), 2.10 (1 H, dd, J = 10.4, 1.8 Hz, CH2-7), 1.85 (1 H, d, J = 1.8 Hz, H-4), 1.58 (1 H, ddd, J = 12.4, 10.1, 3.2 Hz, CH2-6), 1.52 (1 H, ddd J = 13.2, 6.5, 3.2 Hz, CH2-5), 1.33 (1 H, ddd, J = 12.4, 6.5, 1.3 Hz, CH2-6), 1.25 (1 H, ddd, J = 13.2, 10.1, 1.3 Hz CH2-5), 1.21 (1 H, d, J = 10.4 Hz, CH2-7), 0.99 [3 H, s, C(CH3)2], 0.95 [3 H, s, C(CH3)2]. 13C NMR (CDCl3): 169.9, 136.5, 120.5, 93.7, 49.2, 49.1, 44.0, 34.8, 32.1, 25.7, 24.4, 24.1, 22.2. The NMR assignments were aided by 13C DEPT, 1H-1H and 13C-1H COSY spectroscopy. IR (KBr): 1759 (s), 1667 (w), 1120 (w), 975 (w) cm-1. MS (EI): m/z (%): 207 (40) [M + H], 191 (13), 133 (24), 138 (72), 123 (100), 121 (67), 108 (56), 95 (64), 79 (45), 67 (94).
Compound 8a: [α]D 20 +35 (c 2.01 CHCl3); mp 73-75 °C. 1H NMR (300 MHz, CDCl3): δ = 6.25 (1 H, d, J = 2.9 Hz, =CH2), 5.61 (1 H, d, J = 2.5 Hz, =CH2), 2.95 (1 H, dq, J = 10.8, 2.8 Hz, H-6), 2.54 (1 H, ddt, J = 13.5, 10.8, 2.2 Hz, CH2-7), 2.22 (1 H, ddd, J = 12.0, 6.0, 2.2 Hz H-8), 2.21 (1 H, d, J = 5.4 Hz, H-1), 1.93 (1 H, dddd, J = 11.0, 6.0, 5.4, 2.2 Hz, CH2-10), 1.76 (1 H, dt, J = 13.5, 3.3 Hz, CH2-7), 1.47 (3 H, s, CH3, C-2), 1.28 [3 H, s, (CH3)2C<], 1.02 (1 H, dd, J = 12.0, 11.0 Hz, CH2-10), 0.90 [3 H, s, (CH3)2C<]. IR (KBr): 1758 (s), 1655 (m), 1288 (m), 1066 (m), 1016 (m) cm-1. MS (EI): m/z (%) = 207 (100) [M + H], 191 (16), 136 (41), 151 (21), 135 (22), 121 (26), 107 (25), 91 (34), 79 (44).
Compound 9a: [α]D 20 -30 (c 1.29 CHCl3).
Compound 10: yield 70%; n D 20 1.4673. 1H NMR (300 MHz, CDCl3): δ = 4.14 (2 H, q, J = 7.1 Hz, CH3CH2O-), 2.80 (1 H, dq, J = 11.3 Hz, J 5 = 1.5 Hz, CH2), 2.57 (1 H, dq, J = 11.3, 1.5 Hz, CH2), 2.14 [3 H, t, J 5 = 1.5 Hz, C(O)CH3], 1.70 and 1.63 [2 H, two d, J = 14.6 Hz (CH3)3CCH2, AB system], 1,37 [3 H, s, (CH3)CO], 1.26 (3 H, t, J = 7.1 Hz, CH3CH2O), 0.99 [9 H, s, (CH3)3CCH2]. 13C NMR (CDCl3): 166.7, 166.6, 101.0, 89.2, 59.3, 53.2, 43.5, 31.2, 28.2, 14.5. IR (film): 2960 (s), 1708 (s), 1660 (s), 1268 (m), 1224 (m), 1096 (m) cm-1. MS (EI): m/z (%) = 241 (11) [M + H], 222 (21), 207 (20), 198 (42), 166 (43), 141 (100), 111 (56), 95 (70), 67 (43).