Novel One-Pot Cycloisomerization-Knoevenagel Condensation Sequences with Yne Allyl Alcohols

Christoph J. Kressierer; Thomas J. J. Müller

doi:10.1055/s-2005-871556

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Synlett 2005(11): 1721-1725
DOI: 10.1055/s-2005-871556

LETTER

Novel One-Pot Cycloisomerization-Knoevenagel Condensation Sequences with Yne Allyl Alcohols

Christoph J. Kressierer, Thomas J. J. Müller*
Organisch-Chemisches Institut der Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax: +49(6221)546579; e-Mail: Thomas_J.J.Mueller@urz.uni-heidelberg.de;

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Publication History

Received 27 April 2005
Publication Date:
28 June 2005 (online)

Abstract
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Abstract

The sequential Pd-catalyzed cycloisomerization-Knoevenagel condensation of alkyne allyl alcohols 1 and CH-acidic compounds, such as acetylacetone (2a), dimethyl malonate (2b) or malononitrile (2c), furnishes the 2,6-dienes 3 in moderate to good yield. Upon reacting 1,3-cyclohexadione (4a) or dimedone (4b) under the same reaction conditions pseudo-three-component products 5 are formed as a consequence of a consecutive cycloisomerization-condensation-addition sequence in 57-88% yield.

Key words

additions - alkynes - catalysis - condensations - ene reactions

References

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7

Typical Procedure (3d, Entry 1).
To a solution of 41 mg (0.04 mmol) of Pd₂(dba)₃·CHCl₃ in 10 mL of dichloroethane were added 0.198 g (1.00 mmol) of 1a and 41 mg (0.2 mmol) of rac-N-acetyl phenylalanine. The reaction mixture was stirred at r.t. for 45 min. Then, 0.017 g (0.2 mmol) of piperidine, 0.198 g (1.50 mmol) of dimethyl malonate (2b), and 1.00 g of 4 Å MS were added and the mixture was stirred at r.t. for 18 h before it was diluted with 150 mL of Et₂O. After filtration the solvents were evaporated in vacuo and the residue was chromatographed on silica gel to give 0.160 g (51%) of 3d as a pale yellow oil; R _f (n-hexane-Et₂O 1:2, SiO₂) = 0.58. IR (neat): 2953 (m), 2899 (w), 2848 (w), 1734 (s), 1635 (m), 1437 (m), 1372 (m), 1249 (s), 1107 (m), 1063 (s), 839 (s), 768 (m), 749 (m), 693 (w) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.07 (s, 9 H), 2.32-2.45 (m, 1 H), 2.51-2.63 (m, 1 H), 2.70-2.84 (m, 1 H), 3.51 (dd, J = 6.1, 8.8 Hz, 1 H), 3.77 (s, 3 H), 3.82 (s, 3 H), 3.94 (dd, J = 6.8, 8.8 Hz, 1 H), 4.27-4.32 (m, 2 H), 5.41-5.45 (m, 1 H), 6.96-7.03 (m, 1 H). ¹³C NMR (125.8 MHz, CDCl₃): δ = -0.6 (CH₃), 32.6 (CH₂), 45.4 (CH), 52.3 (CH₃), 52.4 (CH₃), 70.6 (CH₂), 72.2 (CH₂), 119.0 (CH), 129.1 (C_quat.), 147.5 (CH), 158.3 (C_quat.), 164.1 (C_quat.), 165.6 (C_quat.). MS (EI, 70 eV): m/z (%) = 312 (6) [M⁺], 297 (56) [M - CH₃]⁺, 280 (78) [M - CH₃OH]⁺, 265 (54) [M - CH₃ - CH₃OH]⁺, 155 (100), 126 (39), 89 (46), 73 (90) [Si(CH₃)₃]⁺. Anal. Calcd for C₁₅H₂₄O₅Si (312.4): C, 57.66; H, 7.74. Found: C, 57.38; H, 7.67.

8

All compounds have been fully characterized spectroscopically and by correct elemental analysis or HRMS.

9

Typical Procedure (5b, Entry 2).
To a solution of 41 mg (0.04 mmol) of Pd₂ ₍dba)₃·CHCl₃ in 10 mL of dichloroethane were added 0.316 g (1.00 mmol) of 1b and 9 mg (0.2 mmol) of formic acid. The reaction mixture was stirred at r.t. for 45 min. Then, 0.017 g (0.2 mmol) of piperidine, 0.235 g (2.10 mmol) of dimedone (4b), and 1.00 g of 4 Å MS were added and the mixture was stirred at r.t. for 18 h before it was diluted with 150 mL of Et₂O. After filtration the solvents were evaporated in vacuo and the residue was chromatographed on silica gel to give 0.388 g (74%) of 5b as colorless crystals, mp 67 °C; R _f (n-hexane-Et₂O 2:1, SiO₂) = 0.47. IR (KBr): 2952 (w), 2638 (w), 1734 (m), 1590 (s), 1434 (w), 1374 (w), 1268 (m), 1197 (m), 1170 (w), 1142 (w), 1122 (w), 1066 (w), 1029 (w), 697 (w) cm^-1.¹H NMR (300 MHz, CDCl₃): δ = 1.54-2.00 (m, 6 H), 2.23-2.41 (m, 4 H), 2.44-2.62 (m, 6 H), 2.86-3.01 (m, 1 H), 3.16-3.35 (m, 2 H), 3.65 (s, 3 H), 3.71 (s, 3 H), 3.99-4.08 (m, 1 H), 6.24-6.28 (m, 1 H), 7.11-7.35 (m, 5 H), 11.53-12.40 (br, 1 H), 13.03 (s, 1 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 19.6 (CH₂), 19.8 (CH₂), 27.7 (CH), 32.5 (CH₂), 32.6 (CH₂), 33.2 (CH₂), 33.3 (CH₂), 33.4 (CH₂), 38.6 (CH₂), 38.8 (CH₂), 42.9 (CH), 52.5 (CH₃), 52.6 (CH₃), 58.9 (C_quat.), 116.0 (C_quat.), 117.9 (C_quat.), 122.2 (CH), 126.1 (CH), 128.0 (CH), 128.1 (CH), 137.5 (C_quat.), 144.1 (C_quat.), 171.7 (C_quat.), 171.8 (C_quat.), 190.9 (C_quat.), 191.4 (C_quat.), 191.5 (C_quat.), 191.7 (C_quat.). FAB-MS: m/z (%) = 523 (100) [M]⁺. HRMS: m/z calcd for C₃₀H₃₅O₈ [M + H]⁺: 523.2332; found: 523.2369. Anal. Calcd for C₃₀H₃₄O₈ (523.6): C, 68.95; H, 6.56. Found: C, 68.58; H, 6.52.