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Synlett 2009(8): 1223-1226  
DOI: 10.1055/s-0028-1216727
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Trialkylamine versus Trialkylphosphine: Catalytic Conjugate Addition of Alcohols to Alkyl Propiolates

David Tejedor*a,b, Alicia Santos-Expósitoa,b, Gabriela Méndez-Abta,b, Catalina Ruiz-Pérezc, Fernando García-Tellado*a,b
a Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, Astrofísico Francisco Sánchez 3, 38206 La Laguna, Tenerife, Spain
Fax: +34(922)260135; e-Mail: fgarcia@ipna.csic.es; e-Mail: dtejedor@ipna.csic.es;
b Instituto Canario de Investigación del Cáncer, http://www.icic.es
c Departamento de Física Fundamental II, Universidad de La Laguna, Astrofísico Francisco Sánchez s/n,38204 La Laguna, Tenerife, Spain
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Publikationsverlauf

Received 13 January 2009
Publikationsdatum:
17. April 2009 (online)

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Abstract

The conjugate addition of activated propargylic alcohols to alkyl propiolates is shown to be catalyst-dependent. Whereas trialkylamines catalyze the expected 1,4-adition of the alcohol on the alkynoate to give the β-alkoxyacrylate derivative, the trialkylphosphine-catalyzed reaction affords densely functionalized bicyclic hexahydrofuro[2,3-b]furan derivatives. A mechanistic proposal for the phosphine-catalyzed addition of alcohols to alkyl propiolates according with these observations is presented.

Key words

catalysis - amines - phosphorus - bicyclic compounds - alkynes

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11

We have shown that under different reaction conditions
1,3-dioxolane derivatives can be obtained regardless of the catalyst used, see reference 9a.

13

The Et3N in CH2Cl2 proved to be the best catalytic system.

14

Six different isomers were isolated with relative intensities of 0.81:0.72:0.94:1.00:0.07:0.01 and identified on the basis of their NMR spectra and the X-ray crystal structure analysis of one of the isomers.

17

Unactivated propargylic alcohols behave as expected affording the corresponding product 1 (see ref. 1).

18

Experimental Details for the Et 3 N-Catalyzed Addition of Activated Propargylic Alcohols to Methyl Propiolate: Product 2a was synthesized from 4a as described in Scheme  [³] . A cooled (0 ˚C) solution of propargylic alcohol and methyl propiolate (1.0 mmol of each) in CH2Cl2 (5 mL) was stirred with Et3N (0.2 mmol) until a TLC showed complete starting material disappearance. Solvent and excess reagents were removed under reduced pressure and the product was isolated by flash column chromatography (silica gel, n-hexane-EtOAc). ¹H NMR (400 MHz, CDCl3): δ = 1.30 (t, J = 7.2 Hz, 3 H), 3.69 (s, 3 H), 4.23 (q, J = 7.2 Hz, 2 H), 4.62 (s, 2 H), 5.31 (d, J = 12.5 Hz, 1 H), 7.52 (d, J = 12.5 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 13.9, 51.3, 57.5, 62.4, 79.3, 79.7, 98.6, 152.5, 160.2, 167.3. IR (CHCl3): 3021.7, 2248.3, 1710.2, 1629.6, 1259.6, 1137.4 cm-¹. Anal. Calcd for C10H12O5: C, 56.60; H, 5.70. Found: C, 56.61; H, 5.65. MS: m/z (%) = 212 (21) [M+], 181 (86), 156 (95), 139 (70), 125 (50), 67 (95), 66 (100), 55 (69).
Experimental Details for the Bu 3 P-Catalyzed Addition of Activated Propargylic Alcohols to Methyl Propiolate: Product 5a was synthesized from 4a as described in Scheme  [4] . A cooled (-78 ˚C) solution of propargylic alcohol and methyl propiolate (1.0 mmol of each) in CH2Cl2 (5 mL) was stirred with Bu3P (0.8 mmol) for a few minutes at
-78 ˚C and allowed to react without further cooling for 1 h (lower amounts of Bu3P slow down the reaction while higher temperatures have a negative impact on the overall yield). After the reaction was completed, solvent and excess reagents were removed under reduced pressure. Product was isolated by flash column chromatography as a mixture of two isomers (silica gel, n-hexane-EtOAc), i.e. a mixture of 2Z,2′Z (minor) and 2Z,2′E (major) isomers. Data for major isomer: ¹H NMR (500 MHz, CDCl3): δ = 1.25 (t, J = 6.9 Hz, 3 H), 1.27 (t, J = 6.9 Hz, 3 H), 3.75 (s, 3 H), 4.14-4.21 (m, 4 H), 4.59 (dd, J = 2.0, 15.0 Hz, 1 H), 4.67 (dd, J = 2.1, 15.0 Hz, 1 H), 5.09 (dd, J = 2.8, 16.8 Hz, 1 H), 5.18 (dd, J = 2.7, 16.8 Hz, 1 H), 5.80 (s, 1 H), 5.90 (t, J = 2.0 Hz, 1 H), 6.27 (t, J = 2.7 Hz, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 14.06, 14.07, 52.9, 60.5, 61.0, 67.5, 71.6, 73.1, 113.1, 114.2, 117.5, 155.9, 156.0, 165.2, 165.8, 168.1. IR (CHCl3): 3017.2, 1734.8, 1711.6, 1667.7, 1374.1, 1266.1, 1228.5, 1155.9
cm-¹. Anal. Calcd for C16H20O8: C, 56.47; H, 5.92. Found: C, 56.43; H, 6.03. MS: m/z (%) = 340 (6.0) [M+], 295 (61), 294 (100), 166 (69), 163 (55), 77 (49), 59 (38), 51 (35).