Diethylaminosulfur Trifluoride (DAST)

DAST has proven itself to be an extremely popular reagent for nucleophilic fluorination, due to its ease of handling and versatility. It has regularly been employed in a myriad selective fluorinations of alcohols, alkenols, carbohydrates, ketones, sulfides, epoxides, thioethers, and cyanohydrins. In addition some novel organic cyclizations are possible when DAST is employed as a reagent.¹

Fluorodeoxygenation was achieved using DAST in a preparatively simple synthesis of 5,5-difluoropipecolic acid from glutamic acid (Scheme 5).²

1,2,2-Trifluorostyrenes can be synthesized using a sequential reaction on the parent a-(trifluoromethyl)phenylethanol with DAST, followed by dehydrohalogenation with lithium bis(trimethylsilyl)amide (LHMDS). This method achieves the trifluorostyrene without requirement of palladium coupling (Scheme 6).³

DAST was recently used to obtain fluorinated analogues of 3,6-dibromocarbazole piperazine derivatives of 2-propanol (Scheme 7). A series of these analogues are described as the first small and potent modulators of the cytochrome c release triggered by Bid-induced Bax activation in a mitochondrial assay.⁴

The synthesis of a,a-difluoroamides via direct fluorination was recently reported using DAST as the fluorinating reagent in a one-pot reaction (Scheme 8). Decreasing the molar ratio of DAST to substrate resulted in the formation of the respective a-ketoamide.⁵

a-Fluorosulfides and secondary alcohols were coupled by Yb(OTf)3 to generate O,S-acetals, which are key intermediates in the assembly of ciguatoxins. In their synthesis, hydrogen was directly converted to fluorine using DAST and a catalytic amount of SbCl3 to make the a-fluorosulfide (Scheme 9).⁶