462996-09-4Relevant academic research and scientific papers
Purification of fluorous Mitsunobu reactions by liquid-liquid extraction
Curran, Dennis P.,Bajpai, Reena,Sanger, Elizabeth
, p. 1621 - 1624 (2007/10/03)
Solvent tuning and partition coefficient measurements have identified suitable reagent and solvent combinations for the purification of fluorous Mitsunobu reaction products. The crude reaction mixtures are partitioned between 2/1 HFE-7100/FC-72 and DMF/10% water to provide reagent (fluorous) and product (organic) fractions.
Separation tagging with cyclodextrin-binding groups: Mitsunobu reactions with bis-(2-(1-adamantyl)ethyl) azodicarboxylate (BadEAD) and bis-(1-adamantylmethyl) azodicarboxylate (BadMAD)
Dandapani, Sivaraman,Newsome, Jeffery J.,Curran, Dennis P.
, p. 6653 - 6656 (2007/10/03)
A new method for separation tagging with cyclodextrin-binding groups is introduced and is exemplified in the context of the Mitsunobu reaction with adamantyl tags. HPLC experiments showed that molecules containing adamantyl groups were especially well retained on Sumichiral OA7500 β-methylated cyclodextrin bonded silica columns relative to many other types of molecules. Two new Mitsunobu reagents, bis-(1-adamantylmethyl) azodicarboxylate (BadMAD) and bis-(2-(1-adamantyl)ethyl) azodicarboxylate (BadEAD), were prepared, used in typical Mitsunobu reactions and separated with both β-methylated cyclodextrin bonded silica and standard silica.
Second generation fluorous DEAD reagents have expanded scope in the Mitsunobu reaction and retain convenient separation features
Dandapani, Sivaraman,Curran, Dennis P.
, p. 8751 - 8757 (2007/10/03)
First generation fluorous DEAD reagent bis(perfluorohexylethyl)azo dicarboxylate (C6F13(CH2)2O 2-CN=NCO2(CH2)2C6F13, F-DEAD-1) has been shown to underperform relative to diisopropylazodicarboxylate in difficult Mitsunobu reactions involving hindered alcohols or less acidic pronucleophiles (phenols). Two new second generation fluorous reagents bearing propylene spacers instead of the ethylene spacers show expanded reaction scope while retaining the easy fluorous separation features. Byproducts from "half fluorous" reagent perfluorooctylpropyl tert-butyl azo dicarboxylate (C8F17(CH2)3O 2CN=NCO2tBu, F-DEAD-2) can be removed by fluorous flash chromatography, and byproducts from bis(perfluorohexylpropyl)azo dicarboxylate (C6F13(CH2)3O 2CN=NCO2(CH2)3C6F 13, F-DEAD-3) can be removed by fluorous solid-phase extraction. The new reagents promise to provide general and complementary solutions for separation problems in Mitsunobu reactions without restricting reaction scope.
Fluorous Mitsunobu reagents and reactions
Dandapani, Sivaraman,Curran, Dennis P.
, p. 3855 - 3864 (2007/10/03)
A fully fluorous Mitsunobu reaction procedure is introduced. This employs both existing [(C6F13CH2CH2C6H 4)2PPh] and new [C8F17CH2CH2C6H 4PPh2] fluorous phosphines and a new fluorous azodicarboxylate (C6F13CH2CH2OC(O)N=NCOOCH 2CH2C6F13). A procedure involving parallel reactions with representative nucleophiles and alcohols under typical Mitsunobu conditions in THF followed by rapid solid phase extraction (spe) over fluorous silica provides clean products in excellent yields. The fluorous fraction containing the oxidized phosphine oxide and the reduced hydrazide can be readily separated and the starting reagents can be regenerated by appropriate redox reactions in high yield for reuse.
