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Synlett 2009(16): 2605-2608  
DOI: 10.1055/s-0029-1218019
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Ring-Conformer Effects of the Cyclopropyl Group: First Use of trans-(2R,3R)-Cyclopropanecarbaldehydes as Electrophiles in Diastereoselective Baylis-Hillman Reaction

Palakodety Radha Krishna*, S. Kishore, P. Srinivas Reddy
D-211, Discovery Laboratory, Organic Chemistry Division-III, Indian Institute of Chemical Technology, Hyderabad 500 607, India
Fax: +91(40)27160387; e-Mail: prkgenius@iict.res.in;
Further Information

Publication History

Received 22 July 2009
Publication Date:
10 September 2009 (online)

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Abstract

trans-(2R,3R)-Cyclopropanecarbaldehydes are used as novel electrophiles in the Baylis-Hillman reaction to afford adducts in good yields (75-85%) and diastereoselectivities (60-90%).

Key words

trans-(2R,3R)-cyclopropanecarbaldehydes - Baylis-Hillman reaction - electrophiles - diastereoselectivity

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General Experimental Procedure
To a cold solution (0 ˚C) of cyclopropanecarbaldehyde (1.0 mmol) in DMSO were added DABCO (0.5 mmol) and the activated alkene (1.5 mmol) and the reaction mixture stirred for 12-15 h at r.t. After completion of reaction (by TLC), the reaction mixture was partitioned between Et2O (2 × 50 mL) and H2O (1 × 60 mL). The organic phase was washed with brine (2 × 50 mL), dried (Na2SO4), and evaporated under reduced pressure. The residue was purified by column chromatography to afford products 4a-h and 5a-h in good yields (75-85%).

14

Spectral Data of Selected Compounds
Compound 4a: thick yellow syrup; [α]D ²5 +1.07 (c 1.55, CHCl3). ¹H NMR (200 MHz, CDCl3): δ = 7.31-7.25 (m, 5 H), 6.21 (s, 0.95 H), 6.15 (s, 0.05 H), 5.83 (s, 0.95 H), 5.80 (s, 0.05 H), 4.46 (s, 2 H), 4.37 (dd, 1 H, J = 4.0, 8.0 Hz), 4.21 (q, 2 H, J = 7.3 Hz), 3.42 (t, 2 H, J = 6.5 Hz), 2.55 (t, 1 H, J = 6.5 Hz), 2.39 (t, 1 H, J = 7.3 Hz), 2.06-1.71 (m, 1 H), 1.56 (q, 2 H, J = 6.5 Hz), 1.36-1.21 (m, 15 H). ¹³C NMR (75 MHz, CDCl3): δ = 164.1, 142.3, 138.6, 128.2, 127.5, 127.3, 124.8, 72.7, 70.6, 70.4, 60.7, 42.8, 38.8, 31.8, 29.2, 29.1, 26.0, 24.4, 23.8, 14.0. HPLC column: Waters HRC18, 300 × 309 mm, 6 µm, 50% MeCN in H2O, flow rate: 1 mL/min, t R(major) = 2.783 min, t R(minor) = 3.639 min. IR (neat): 3440, 2928, 2855, 1716 cm-¹. ESI-MS: m/z = 400 [M - H]+, 441 [M + 39]+. Anal. Calcd (%) for C25H34O4: C, 74.59; H, 9.51. Found: C, 74.61, H, 9.50.
Compound 4g: colorless syrup; [α]D ²5 -109.1 (c 0.85, CHCl3). ¹H NMR (200 MHz, CDCl3): δ = 6.23 (s, 0.15 H), 6.18 (s, 0.85 H), 6.09 (d, 0.15 H, J = 2.9 Hz), 5.96 (d, 0.85 H, J = 3.9 Hz), 5.82 (s, 0.15 H), 5.78 (s, 0.85 H), 5.0 (t, 0.15 H, J = 6.2 Hz), 4.86 (t, 0.85 H, J = 6.6 Hz), 4.21 (q, 2 H, J = 7.0 Hz), 3.99 (q, 2 H, J = 3.1 Hz), 3.51 (s, 0.85 Hz), 3.34 (s, 0.15 H), 2.15-1.87 (m, 2 H), 1.50-1.45 (m, 2 H), 1.40-1.25 (m, 9 H). ¹³C NMR (75 MHz, CDCl3): δ = 167.3, 131.5, 127.2, 105.8, 105.5, 105.3, 86.1, 86.0, 85.8, 85.2, 81.4, 71.9, 58.1, 57.2, 36.4, 35.3, 26.8, 26.3, 26.1. HPLC column: Waters HRC18, 300 × 309 mm, 6 µm, 50% MeCN in H2O, flow rate: 1 mL/min, t R(major) = 4.496 min, t R(minor) = 8.199 min. IR (neat): 3447, 2924, 2854, 1718, cm-¹; ESI-MS: m/z = 341 [M - H]+, 381 [M + 39]+. Anal. Calcd (%) for C17H26O7: C, 59.64; H, 7.65. Found: C, 59.70; H, 7.58.