Publication Cover
Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic Chemistry
Volume 39, 2009 - Issue 12
918
Views
10
CrossRef citations to date
0
Altmetric
Original Articles

One-Pot, Fluoride-Promoted Wittig Reaction

, &
Pages 2178-2195 | Received 17 Oct 2007, Published online: 13 May 2009
 

Abstract

A one-pot, fluoride-promoted Wittig reaction was developed. The reactions of ethyl α-bromoacetate with aliphatic, aromatic, and heteroaromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced α,β-unsaturated esters in good to excellent yields and E-stereoselectivity. Under the same conditions, reactions of ethyl α-bromopropionate, α-bromo acetonitrile, and α-bromoacetophenone with aliphatic and aromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced the expected α,β-unsaturated derivatives in good E-stereoselectivity. The protocol was extended to semistabilized ylides and applied to the synthesis of some combretastatin analogs.

ACKNOWLEDGMENTS

Universitá degli Studi di Milano and MIUR (Ministero dell' Istruzione, dell’ Universitá e della Ricerca) are acknowledged for financial support.

Notes

a Conditions: 1a/n-Bu3P/2/n-Bu4NF = 1:1:1.1:1.2 molar ratio; THF at room temperature.

b 1a/n-Bu3P/2/n-Bu4NF = 1:1:0.5:1.2 molar ratio.

c1H NMR yields of the crude reaction mixture.

d Reaction also carried out at 70°C; after 16 h, 32% yield by 1H NMR of the crude reaction mixture.

e E/Z determined by 1H NMR.

f Reaction carried out also with PPh3 in 86% yield and unchanged diastereoisomeric ratio.

g Mixture of E and Z isomers.

h Both E and Z isomers were isolated and characterized.

i When TBDMS protects the hydroxylic functionality, the reaction yield is 87%.

j SDS: sodium dodecyl sulphate; Ref. 10a.

a Conditions: 1/n-Bu3P/2/n-Bu4NF = 1:1:1.1:1.2; THF at room temperature.

b E/Z determined by 1H NMR.

c The reported yield concerns the E isomer only. By 1H NMR, the crude mixture contains 95% yield of E/Z (72:28) isomers: the E isomer only was purified.

a Conditions:1/n-Bu3P/2/n-Bu4NF = 1:1.1:1.1:1.

b Both E and Z isomers were isolated and characterized.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.