DAST-fluorination

The synthetic paths of fluorinated porphyrins (fluorine atoms or fluoroalkyl chains) are numerous and depend on the fluorination site (periphery or meso position). These syntheses are performed through the use of fluoroalkylated pyrroles, through DAST fluorination, or through direct perfluoroalkylation. Some examples are given next. 

DAST fluorination of 3-ketofuranose does not allow preparation of 3,3-difluor-odeoxyfuranose, because of the steric hindrance of the protected 2-hydroxyI. ... 

Nucleophilic fluorination is particularly useful in the synthesis of 2-fluoro-2-deoxypyranoses (e.g., DAST fluorination, displacement of a leaving group by a fluoride ion, oxirane ring opening with HF-amine complexes). Electrophilic fluorination also allows the synthesis of 2-fluoro-2-deoxypyranoses. 

Difluorocyclopentadiene was prepared via a pyrolysis reaction the difluoro-methylene centre was installed (Eq. 119) using a DAST fluorination [318]. A fluorobutenolide building block was prepared by a Wadsworth-Emmons reaction of isopropylidene glyceraldehyde removal of the ketal protecting group led to the formation (Eq. 120) of the unsaturated lactone in acceptable overall yield... 

Another example of DAST fluorination with retention of configuration in the absence of neighboring group participation is 12)S-hydroxyandrostan-17-one which on reaction with DAST gives 12lS-fluoroandrostan-17-one. ... 

Fluorination with DAST is a powerful tool in carbohydrate chemistry. The reaction usually proceeds in high yield with complete inversion. For fluorinations at a specific site to occur, other reactive groups are usually protected by standard protective groups. On the other hand, in several cases primary hydroxy groups in side chains can be substituted selectively by DAST without protection of ring hydroxy groups. Table 5 shows some recent examples of DAST fluorinations in carbohydrate chemistry, another example is the formation of the fluorinated kanamycin B derivative 15 S2 for earlier work, see ref 38. 

SCHEME 6.23 The regiochemistry of the DAST fluorination can be controlled through protecting groups, anomeric configuration and the cyclic form of the sugar. 

Attempts to prepare diethyl fluoromethylphosphonate by DAST fluorination of diethyl hydroxymethylphosphonate gave very low yields (<2%). A different methodology, involving the conversion of the alcohol into the corresponding triflate and a subsequent nucleophilic displacement with TBAF, provided a safe, cheap, and simple route to diethyl fluoromethylphosphonate, which was isolated in 67% yield (Scheme 3.14). ... 

The synthesis of sofosbuvir was based on the convergent condensation of nucleoside PSI-6206 (10) and a phosphoramidating reagent. The discovery synthesis of PSI-6206 started from cytidine in a linear approach (Scheme 1). Cytidine (29) was selectively benzoylated and silylated to 30, which underwent Swem oxidation and MeLi addition, giving exclusively 2 -a-methyl compound 32. Desilylation and benzoylation of 32 yielded benzoylated 2 -a-methyl compound 33, which was converted to 2 -p-methyl-2 -fluorocytidine 34 by DAST fluorination. Deamination of 34 followed by deprotection provided PSI-6206 (10). 

Figure 6.7 Selected examples ofthe substrate scope ofthe DAST fluorination process of alcohols (products 5-8), aldehydes (products 9 and 10), and carboxylic acids (product 11).

---