Hexafluoroacetone with amidines

The [4+1] cycloaddition of 4,4-bis(trifluoromethyl)-l,3-diazabuta-1,3-diene 18, obtained by a reaction of hexafluoroacetone with an amidine in the presence of a dehydrating agent, to an isonitrile gives 5-(butylimino)-l-(2,6-dimethyl-phenyl)-2-phenyl-4,4-bis(trifluoromethyl)-2-imidazoline 19 in the form of Z and E isomers (92JFC(58)345) (Scheme 20). 

Fluorinated synthons have been used to access fluorinated imidazoles. Reduction of Schiff bases derived from amidines and hexafluoroacetone with SnCl2 gives rise to 5-fluoro-4-trifluoromethylimidazoles 110 (Fig. 3.57). ° ° Because the 5-fluoro substituent is readily displaced by nucleophiles such as alkoxide, cyanide, and others, this procedure provides access to a range of trifluoromefliyl-substituted imidazoles (also see below). 

When hexafluoroacetone reacts with amides, urethanes [25], thioamides [26], amidines [27], sulfonamides [28, 29], sulfinainides [20], and f),0-dialkyl-amido-phosphates [27], the correspondmg semiamidals are formed m nearly quantitative yield The thermal stabihty of these adducts toward the retro reaction increases with the nucleophihcity of the ammo compound [5] Many polyfluonnated carbonyl compounds react likewise [22 22] On treatment of ureas [34], thioureas [34], thioamides [26], and C,77 diarylatmdmes [27, 25] first with hexa- fluoroacetone and then with dehydratmg agents, heterodienes are obtamed (equation 4)... 

Another example of fluorinated pyrimidine synthesis via [5+1] approach using fluorinated Ci synthon was described by Burger in 1980. Amidines 976 react with hexafluoroacetone (HFA) affording adduct 977, which under treatment with POCls-Py generating diazabuta-1,3-dienes 978 spontaneously cyclized into... 

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