3-trifluoromethyl-3- diazirine

Trifluoromethyl)-3//-diazirin-3-yl]arenes, e.g. 36 (R1 = CF3), were introduced as photophores by Brunner et alJ116 to provide a more favorable carbene than the one produced from diazoesters[117 or from aryldiazirines. 118 Both 3//-diazirin-3-ylarenes I8-1201 and the [(3-tri-fluoromethyl)-3//-diazirin-3-yl]arenes (e.g., 36, R = H, CF3, respectively) 116 are more stable in acid than most diazoesters, and photolyze at around 360 nm to generate highly reactive carbenes such as 37. However, these diazirines can photo-isomerize to some extent to the... 

Scheme 11 Photolysis Reactions of [3-(Trifluoromethyl)-3//-diazirin-3-yl]arenes and 3/f-Diazirin-3-ylarenes171...

The synthesis reported by Nassal is based on the Ca-alkylation of diethyl 2-(ace-tylamino)malonate by 3-[4-(bromomethyl)phenyl]-3-(trifluoromethyl)-3//-diazirine (46) (Scheme 12) J122l The precursor for the diazirine-containing alkylating agent is 2,2,2-trifluoro-l-(4-tolyl)ethanone (39).1124 ... 

Acetylamino)-2- 4-[3-(trifluoromethyl)-3//-diazirin-3-yllbenzyl)inalonic Acid (48) [122)... 

The syntheses of 4-[3-(trifluoromethyl)-3//-diazirin-3-yl]arene-containing peptides are carried out in a straightforward manner. In solid-phase syntheses, H-Phe(4-Tmd)-OH [Tmd = 3-(trifluoromethyl)-3//-diazirin-3-yl] is incorporated as the Fmoc-Phe(4-Tmd)-OH (Table 4).[i23,130-133] Solution-phase syntheses of [Phe4(4-Tmd)J-Leu-enkephalin and [Phe2(4-Tmd)J-aspartame employ Boc-Phe(4-Tmd)-OH and are carried out by the mixed anhydride method.1122 Apparently Phe(4-Tmd) is stable in TFA/CH2C12 (1 1) for 30 min at rt 122 or even in neat TFA for 15 min at 0°CJ134] A post-synthetic modification of a free peptide has been carried out by the mixed anhydride mediated coupling of 4-[3-(trifluoromethyl)-3/7-diazirin-... 

Scheme 5 Preparation and examples of diazirines. (a) Synthetic scheme for preparation of 3-aryl-3-(trifluoromethyl)-3//-diazirines. (b) Examples of diazirine functionalized compounds...

The synthetic scheme often applied for the preparation of 3-aryl-3-(trifluoromethyl)-3//-diazirine nowadays is shown in Scheme 5a [60]. It starts by lithiation of an aryl bromide (38), which subsequently reacts with /V-ftrifluoroacetyl)piperidine 39 (easily prepared from trifluoroacetic anhydride and piperidine) under the formation of trifluoroacetophenone 40. Next, the ketone is converted into the corresponding oxime 41, after which the hydroxyl group is converted into its tosylate (42). Reaction with liquid ammonia (usually under pressure) allows the installment of the diaziridine group (43). Subsequent oxidation with iodine finally results in the diazirine (44). This five-step reaction sequence is especially compatible with acid-labile protective groups, which are often used to protect and/or install functionalities at the R position. 

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