Metalations of imidazoles

Synthesis of imidazole-containing analogues of farnesyl pyrophosphate and evaluation of their biological activity on protein farnesyltransferase

“…Our starting material was the N-SEM-imidazole 3a, easily obtained by classical protection of the N-1 imidazole with SEM-Cl. [13] The deprotonation with nBuLi of the N-1 protected imidazole ring 3a [14] followed by the addition on the 3-methylcrotonaldehyde 4a led to the allylic alcohol 5a which was easily oxidized by MnO 2 [15]. The direct addition of the carbanion on the methyl ester of 3-methylcrotonic acid was considered but the high reactivity of the formed ketone 6a to nucleophilic addition led to a mediocre yield (26%).…”

“…Compound 17 (38.9 mg, 17% yield) was obtained after purification as a colorless oil; 1 H NMR (300 MHz, CDCl 3 ) : 1.60 (bs, 6H); 1.69 (bs, 3H); 1.69 (bs, 3H); 1.93-2.14 (m, 8H); 2.28-2.44 (m, 4H); 5.11 (m, 3H). 13 …”

“…13 (26): A solution of diethyl 2-(diethoxyphosphoryl)succinate 25 (500 mg, 1.6 mmol, 1.5 equiv.) in anhydrous THF (0.7 mL) was added to a cooled (0°C) suspension of NaH (60% in oil, 155 mg, 3.9 mmol, 1.7 equiv.)…”

Novel structural analogs of glyphosate based on azoles. 1. Synthesis of 1H-imidazoles containing carboxyl and phosphoryl groups in the ring

“…In addition, the carboxyl group can be used as a C(2)-protecting group in the lithiation of N-substituted imidazoles at the 5 position of the ring [17]. None the less we decided to repeat the synthesis of the precursor of imidazole 5 by the scheme reported above using N-SEM protection which can be removed using F -in anhydrous media [18]. Carrying out this synthesis gave unexpected results in that the imidazole phosphorylation occurred only at the ring position 2 despite the fact that TBDMS protection (which was stable to migration) had been used for blocking this position.…”

Thio acid-mediated conversion of azides to amides – Exploratory studies en route to oroidin alkaloids

“…Reaction of the deprotonated imidazole with (TMSO) 2 provided the 2-oxo derivative 12 in low but usable yield. 19 Desilylation of each of these derivatives was accomplished with TBAF and introduction of the allylic azide was performed as before with DPPA and DBU providing the corresponding allylic azides 13–15 (Table 1). In the case of the 2-azido derivative 13 , the DMAS group was removed by acid-catalyzed methanolysis to give the free imidazole 16 in excellent yield and mild conditions (Scheme 1).…”