TY - JOUR
T1 - Electrophilic fluorination-nucleophilic addition reaction mediated by selectfluor
T2 - mechanistic studies and new applications
AU - Vincent, Stephane
AU - Burkart, Michael D.
AU - Tsai, Chungying
AU - Zhang, Zhiyuan
AU - Wong, Chi-Huey
PY - 1999
Y1 - 1999
N2 - The electrophilic fluorination−nucleophilic addition reaction with Selectfluor-type reagents upon glycals has been studied and optimized. This reaction leads to selective fluorination at the 2-position with concomitant nucleophilic addition to the anomeric center. To understand the stereochemical outcome of this process, a mechanistic study has led to the discovery that, in the fucose series, Selectfluor adds specifically in a syn manner, yielding a 1-[TEDA-CH2Cl]-2-fluoro saccharide that anomerizes slowly to a more stable intermediate. The anomeric α/β distribution was studied as a function of reactants and conditions, and it was found that a judicious choice of protective group strategy can improve the stereoselectivity of both fluorination and nucleophilic addition. Furthermore, a hypersensitive radical probe was used to probe the reaction, and no product characteristic of a radical process was isolated, suggesting that no single electron transfer occurs during the attack of the glycal on Selectfluor. The importance of solvent effect, Selectfluor counterion, and stepwise procedure has also been discussed. This study has brought an important improvement of yields and a broader range of allowed nucleophiles such as secondary alcohols of carbohydrates, amino acids, phosphates, or phosphonates. This optimized process was further applied to the modification of important bioactive molecules, including the synthesis of fluorinated daunomycin and oleandrin analogues and the oxidation of thioglycosides to the corresponding sulfoxides.
AB - The electrophilic fluorination−nucleophilic addition reaction with Selectfluor-type reagents upon glycals has been studied and optimized. This reaction leads to selective fluorination at the 2-position with concomitant nucleophilic addition to the anomeric center. To understand the stereochemical outcome of this process, a mechanistic study has led to the discovery that, in the fucose series, Selectfluor adds specifically in a syn manner, yielding a 1-[TEDA-CH2Cl]-2-fluoro saccharide that anomerizes slowly to a more stable intermediate. The anomeric α/β distribution was studied as a function of reactants and conditions, and it was found that a judicious choice of protective group strategy can improve the stereoselectivity of both fluorination and nucleophilic addition. Furthermore, a hypersensitive radical probe was used to probe the reaction, and no product characteristic of a radical process was isolated, suggesting that no single electron transfer occurs during the attack of the glycal on Selectfluor. The importance of solvent effect, Selectfluor counterion, and stepwise procedure has also been discussed. This study has brought an important improvement of yields and a broader range of allowed nucleophiles such as secondary alcohols of carbohydrates, amino acids, phosphates, or phosphonates. This optimized process was further applied to the modification of important bioactive molecules, including the synthesis of fluorinated daunomycin and oleandrin analogues and the oxidation of thioglycosides to the corresponding sulfoxides.
U2 - 10.1021/jo990686h
DO - 10.1021/jo990686h
M3 - Article
SN - 0022-3263
VL - 64
SP - 5264
EP - 5279
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 14
ER -