Download PDF
Synlett 2003(7): 0937-0942
DOI: 10.1055/s-2003-39297
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Ring-Opening of Lactones with Alkynyltrifluoroborates: A New Route to Functionalized α-Alkynones

Jan Doubskýa, Ludvík Streinza, Ladislav Lešetickýb, Bohumír Koutek*a
a Institute of Organic Chemistry and Biochemistry, 166 10 Prague 6, Czech Republic
Fax: +420(2)24310177; e-Mail: koutek@uochb.cas.cz;
b Department of Organic Chemistry, Charles University, 120 00 Prague 2, Czech Republic
Further Information

Publication History

Received 18 February 2003
Publication Date:
20 May 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

Alkynyltrifluoroborate salts, readily generated in situ by the addition of BF3˙OEt2 to alkynyllithiums, were shown to mediate the regioselective acyl C-O ring cleavage of 5-, 6-, and 7-membered lactones. This novel, operationally simple and high yielding (85-99%) reaction allows a convenient and rapid access to α-alkynones substituted with valuable functional groups.

Key words

alkynes - lactones - ring-opening - alkynyltrifluoroborates - hydroxy α-alkynones

21

Low yields of alkynone intermediates were observed when conditions analogous to those used in the original protocol were employed to transform lactones into spiroacetals. [10c] [d]

23

General Procedure for the Synthesis of Alkynones 4: To a solution of alkyne 1 (8 mmol) in dry THF (25 ml) at -78 °C, n-BuLi (5 mL, 1.6 M, 8 mmol) was slowly added, maintaining an argon atmosphere. The reaction mixture was stirred for 20 min, allowed to warm to about -30 °C. The solution was cooled to -78 °C again, and BF3˙Et2O (1 mL, 7.9 mmol) was added dropwise. Stirring was continued for 10 min, and then lactone 3 (7.2 mmol) was added in one portion via syringe. The resulting mixture was allowed to warm to room temperature within 1 h, a solution of saturated NH4Cl-NH3(aq) 2:1 (5 mL) was added, the mixture was poured into water (50 mL), and extracted with Et2O (4 × 25 mL). The combined ethereal layers were washed with brine, dried briefly with MgSO4, and evaporated to afford the crude product as a slightly yellow oil. The crude material was purified by chromatography on silica gel (hexane/10-30% EtOAc) to yield the alkynone 4.
Selected analytical data:4a: 1H NMR (200 MHz, CDCl3): δ = 1.72 (br s, 1 H), 1.91 (m, 2 H, CH2), 2.64 (m, 2 H, CH2), 2.68 (t, 2 H, J = 6.7 Hz), 3.64 (t, 2 H, J = 6.7 Hz), 3.65 (t, 2 H, J = 6.1 Hz), 4.56 (s, 2 H), 7.34 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 20.44, 26.74, 42.08, 61.77, 67.12, 73.08, 81.33, 91.18, 127.70 (2 C), 127.83, 128.45 (2 C), 137.65, 187.82. IR (CHCl3): 3489 (br, OH), 2217 (C≡C), 1670 (C=O) cm-1. GC-MS (EI); m/z (%): 246 (<1) [M+], 228 (2), 159 (5), 105 (8), 91 (100), 77(19), 65 (20).
4b: 1H NMR (200 MHz, CDCl3): δ = 1.32 (d, 3 H, J = 6.2 Hz), 1.72 (bs, 1 H), 1.91 (m, 2 H, CH2), 2.61 (m, 2 H, CH2), 2.66 (m, 2 H, CH2), 3.65 (t, 2 H, J = 6.2 Hz), 3.75 (m, 1 H, CH), 4.54 (d, 1 H, J = 11.6 Hz), 4.60 (d, 1 H, J = 11.6 Hz), 7.34 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 19.73, 26.61, 26.76, 42.13, 61.77, 70.80, 72.57, 82.02, 91.20, 127.61 (2 C), 127.71, 128.42 (2 C), 138.09, 187.83. IR (CHCl3): 3472 (br, OH), 2216 (C≡C), 1670 (C=O) cm-1. GC-MS (EI); m/z (%): 259 (<1) [M+ - 1], 198 (5), 169 (3), 105 (5), 91 (100), 77 (21), 65 (18).
4c: 1H NMR (200 MHz, CDCl3): δ = 1.52 (d, 3 H, J = 6.7 Hz), 1.95 (tt, 2 H, J = 6.1 Hz and 6.9 Hz), 2.73 (t, 2 H, J = 6.9 Hz), 3.68 (t, 2 H, J = 6.1 Hz), 4.37 (q, 1 H, J = 6.7 Hz), 4.51 (d, 1 H, J = 11.6 Hz), 4.78 (d, 1 H, J = 11.6 Hz), 7.35 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 21.29, 26.55, 42.12, 61.70, 64.24, 71.10, 83.96, 91.58, 127.95, 127.97 (2 C), 128.48 (2 C), 137.23, 187.32. IR (CHCl3): 3500 (br, OH), 2212 (C≡C), 1676 (C=O) cm-1. GC-MS (EI); m/z (%): 228(3) [M+ - 18], 185(11), 105(10), 91(100), 77(43), 65(29).
4d: 1H NMR (400 MHz, CDCl3): δ = 1.06 (s, 9 H, 3 × CH3), 1.21 (d, 3 H, J = 6.1 Hz), 1.61 (br s, 1 H), 1.88 (tt, 2 H, J = 6.2 Hz and 7.1 Hz), 2.47 (m, 2 H, CH2), 2.62 (t, 2 H, J = 7.1 Hz), 3.64 (t, 2 H, J = 6.2 Hz), 4.04 (m, 1 H, CH), 7.41 (m, 6 H), 7.67 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 19.16, 23.08, 26.71, 26.87 (3 C), 29.49, 42.09, 61.83, 67.43, 82.20, 91.61, 127.63 (4 C), 129.75 (2 C), 133.76 (2 C), 135.75 (4 C), 187.77. IR (CHCl3): 3482 (br, OH), 2214 (C≡C), 1669 (C=O) cm-1. GC-MS (EI); m/z (%): 407 (<1) [M+ - 1], 390 (3), 333 (100), 289 (38), 259 (31), 233 (66), 211 (71), 135 (85), 105 (42), 77 (34).
4e: 1H NMR (200 MHz, CDCl3): δ = 0.93 (t, 3 H, J = 7.3 Hz), 1.35-1.65 (m, 4 H, 2 × CH2), 1.73 (br s, 1 H), 1.92 (tt, 2 H, J = 7.1 Hz and 6.3 Hz), 2.37 (t, 2 H, J = 6.8 Hz), 2.68 (t, 2 H, J = 7.1 Hz), 3.67 (t, 2 H, J = 6.3 Hz). 13C NMR (100 MHz, CDCl3): δ = 13.42, 18.59, 21.90, 26.76, 29.65, 42.14, 61.80, 80.77, 94.90, 188.11. IR (CHCl3): 3466 (br, OH), 2213 (C≡C), 1670 (C=O) cm-1. GC-MS (EI); m/z (%): 168 (<1) [M+], 150 (24), 124 (19), 109 (100), 79 (68), 67 (25), 53 (34).
4f: 1H NMR (200 MHz, CDCl3): δ = 1.83 (bs, 1 H), 2.00 (tt, 2 H, J = 7.2 Hz and 6.3 Hz), 2.83 (t, 2 H, J = 7.2 Hz), 3.72 (t, 2 H, J = 6.3 Hz), 7.42 (m, 3 H), 7.57 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 26.80, 42.13, 61.78, 87.72, 91.10, 119.84, 128.59 (2 C), 130.72, 133.02 (2 C), 187.82. IR (CHCl3): 3471 (br, OH), 2203 (C≡C), 1664 (C=O) cm-1. GC-MS (EI); m/z (%): 188 (1) [M+], 170 (19), 144 (13), 129 (100), 115 (11), 102 (29), 75 (20).
4g: 1H NMR (200 MHz, CDCl3): δ = 1.45-1.90 (m, 5 H, 2 × CH2 and OH), 2.59 (t, 2 H, J = 7.3 Hz), 2.67 (t, 2 H, J = 6.7 Hz), 3.62 (t, 2 H, J = 6.1 Hz), 3.64 (t, 2 H, J = 6.7 Hz), 4.56 (s, 2 H), 7.35 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 20.08, 20.42, 31.79, 44.98, 62.21, 67.14, 73.07, 81.32, 90.92, 127.69 (2 C), 127.82, 128.44 (2 C), 137.65, 187.89. GC-MS (EI); m/z (%): 242 (3) [M+ - 18], 198 (1), 183 (5), 159 (4), 105 (9), 91 (100), 77 (22), 65 (21).
4h: 1H NMR (200 MHz, CDCl3): δ = 1.32 (d, 3 H, J = 6.1 Hz), 1.57 (m, 2 H, CH2), 1.72 (m, 2 H, CH2), 2.59 (m, 2 H, CH2), 2.61 (m, 2 H, CH2), 3.62 (t, 2 H, J = 6.1 Hz), 3.76 (m, 1 H, CH), 4.53 (d, 1 H, J = 11.6 Hz), 4.60 (d, 1 H, J = 11.6 Hz), 7.34 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 19.74, 20.12, 26.59, 31.79, 45.02, 62.21, 70.80, 72.59, 82.02, 90.95, 127.61 (2 C), 127.71, 128.41 (2 C), 138.09, 187.91. GC-MS (EI); m/z (%): 256 (1) [M+ - 18], 211 (6), 198 (1), 183 (4), 105 (5), 91 (100), 77 (18), 65 (19).
4i: 1H NMR (400 MHz, CDCl3): δ = 1.52 (d, 3 H, J = 6.7 Hz), 1.60 (m, 2 H, CH2), 1.78 (m, 2 H, CH2), 2.63 (t, 2 H, J = 7.2 Hz), 3.66 (t, 2 H, J = 6.3 Hz), 4.37 (q, 1 H, J = 6.7 Hz), 4.52 (d, 1 H, J = 11.7 Hz), 4.78 (d, 1 H, J = 11.7 Hz), 7.36 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 20.03, 21.30, 31.74, 45.03, 62.22, 64.25, 71.09, 83.97, 91.39, 127.95 (3 C), 128.48 (2 C), 137.24, 187.41. IR (CHCl3): 3512 (br, OH), 2212 (C≡C), 1675 (C=O) cm-1. GC-MS (EI); m/z (%): 242 (<1) [M+ - 18], 199 (10), 185 (5), 135 (4), 108 (20), 91 (100), 77 (31), 65 (14).
4j: 1H NMR (400 MHz, CDCl3): δ = 0.93 (t, 3 H, J = 7.4 Hz), 1.44 (m, 2 H, CH2), 1.53-1.63 (m, 4 H, 2 × CH2), 1.70 (br s, 1 H), 1.74 (m, 2 H, CH2), 2.37 (t, 2 H, J = 7.0 Hz), 2.59 (t, 2 H, J = 7.4 Hz), 3.65 (t, 2 H, J = 6.4 Hz). 13C NMR (100 MHz, CDCl3): δ = 13.41, 18.58, 20.13, 21.90, 29.66, 31.80, 45.03, 62.22, 80.78, 94.62, 188.19. IR (CHCl3): 3479 (br, OH), 2213 (C≡C), 1667 (C=O) cm-1. GC-MS (EI); m/z (%): 182 (<1) [M+], 164 (13), 135 (6), 109 (100), 79 (46), 67 (24), 55 (21).
4k: 1H NMR (200 MHz, CDCl3): δ = 1.47 (br s, 1 H), 1.64 (m, 2 H, CH2), 1.83 (m, 2 H, CH2), 2.74 (t, 2 H, J = 7.1 Hz), 3.69 (t, 2 H, J = 6.2 Hz), 7.42 (m, 3 H), 7.57 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 20.22, 31.83, 45.05, 62.25, 87.73, 90.86, 119.89, 128.59 (2C), 130.68, 133.00 (2C), 187.88. IR (CHCl3): 3506 (br, OH), 2204 (C≡C), 1665 (C=O) cm-1. GC-MS (EI); m/z (%): 202 (<1) [M+], 184 (15), 129 (100), 115 (8), 102 (31), 75 (14).
4l: 1H NMR (400 MHz, CDCl3): δ = 1.20 (d, 3 H, J = 6.3 Hz), 1.67 (bs, 1 H), 1.69-1.87 (m, 2 × 1 H, CH2), 2.67 (t, 2 H, J = 6.8 Hz), 2.69 (m, 2 H, CH2), 3.64 (t, 2 H, J = 6.8 Hz), 3.81 (ddq, 1 H, J = 4.3 Hz, 6.3 Hz and 7.9 Hz), 4.56 (s, 2 H, CH2), 7.28-7.38 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 20.44, 23.56, 32.82, 41.85, 67.09, 67.13, 73.07, 81.37, 91.05, 127.69 (2 C), 127.82, 128.45 (2 C), 137.66, 187.95. GC-MS (EI); m/z (%): 242(2) [M+-18], 183 (2), 159 (4), 105 (8), 91 (100), 77 (19), 65 (17).
4m: 1H NMR (400 MHz, CDCl3): δ = 1.19 (d, 3 H, J = 6.0 Hz), 1.32 (d, 3 H, J = 6.1 Hz), 1.65 (br s, 1 H), 1.77 (m, 2 H, CH2), 2.55 (dd, 1 H, J = 17.2 Hz and 6.3 Hz), 2.66 (dd, 1 H, J = 17.2 Hz and 5.3 Hz), 2.69 (t, 2 H, J = 7.3 Hz), 3.76 (m, 1 H, CH), 3.80 (m, 1 H, CH), 4.54 (d, 1 H, J = 11.9 Hz), 4.59 (d, 1 H, J = 11.9 Hz), 7.27-7.35 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 19.73, 23.54, 26.60, 32.84, 41.88, 67.07, 70.78, 72.57, 82.05, 91.07, 127.59 (2C), 127.69, 128.40 (2 C), 138.09, 187.96. IR (CHCl3): 3484 (br, OH), 2214 (C≡C), 1669 (C=O) cm-1. GC-MS (EI); m/z (%): 256 (<1) [M+ - 18], 212 (3), 183 (2), 155 (4), 135 (5), 105 (4), 91 (100), 77 (15), 65 (14).
4n: 1H NMR (400 MHz, CDCl3): δ = 1.38 (m, 2 H, CH2), 1.56 (m, 2 H, CH2), 1.68 (m, 2 H, CH2), 2.55 (t, 2 H, J = 7.5 Hz), 2.67 (t, 2 H, J = 6.6 Hz), 3.62 (t, 2 H, J = 6.2 Hz), 3.64 (t, 2 H, J = 6.6 Hz), 4.56 (s, 2 H, CH2), 7.27-7.38 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 20.41, 23.64, 25.06, 32.29, 45.29, 62.50, 67.15, 73.05, 81.36, 90.71, 127.66 (2 C), 127.80, 128.43 (2 C), 137.66, 187.98. GC-MS (EI); m/z (%): 274 (<1) [M+], 202 (6), 159 (7), 105 (5), 91 (100), 79 (10), 65(12).
4o: 1H NMR (400 MHz, CDCl3): δ = 0.93 (t, 3 H, J = 7.3 Hz), 1.36-1.48 (m, 4 H, 2 × CH2), 1.52 (br s, 1 H), 1.53-1.62 (m, 4 H, 2 × CH2), 1.69 (m, 2 H, CH2), 2.37 (t, 2 H, J = 7.1 Hz), 2.55 (t, 2 H, J = 7.3 Hz), 3.65 (t, 2 H, J = 6.6 Hz). 13C NMR (100 MHz, CDCl3): δ = 13.43, 18.58, 21.90, 23.75, 25.09, 29.68, 32.34, 45.36, 62.56, 80.83, 94.43, 188.27. IR (CHCl3): 3482 (br, OH), 2213 (C≡C), 1666 (C=O) cm-1. GC-MS (EI); m/z (%): 196 (<1) [M+], 178 (2), 167 (4), 124 (42), 109 (100), 95 (9), 79 (41), 67 (12).