Synthesis of New Polycyclic γ‐ and δ‐Lactones upon Activation of, and Nucleophilic Additions to, Diazines: Influence of the Activating Agents

Abstract

The reaction of bis(trimethylsilyl)ketene acetals 2 with N‐heterocycles containing either one or two nitrogen atoms in the presence of triflic anhydride has been examined and the structures of the resulting products compared with those obtained by using methyl chloroformate as the activating agent. Whereas pyridine, pyrazine, quinoxaline and pyrimidine led to the same type of fused δ‐ or γ‐lactones 4, 6, 8, 10 and 11 as with methyl chloroformate, the behaviour of pyridazine appeared to be peculiar. In the presence of methyl chloroformate, this heterocycle led to δ‐lactones 16 via stable dihydropyridazines, with triflic anhydride, the direct formation of γ‐lactones 20 was observed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Overall “Pseudocationic” Trifluoromethylation of Dihydropyridines with Triflic Anhydride

“…Although the reaction of these dihydropyridines with either silica gel or an anhydrous solution of HCl in diethyl ether did not lead to the expected lactones 8 a,b, they did react with I 2 and CuBr 2 to give, as for 2, the corresponding halolactones 9 (Scheme 3). [1,4] However, further studies allowed us to discover a new transformation of these dihydropyridines. Indeed, it appeared that the yield of the dihydropyridines 7 a,b was dependent both on the reaction conditions (order of addition, time of reaction) and on the amount of triflic anhydride used with respect to the starting pyridine: no such an influence was observed when methyl chloroformate was used as the activating agent.…”

Reactions of Bis(trimethylsilyl)ketene Acetals with Several Activated Organic Substrates

“…of methyl chloroformate or triflic anhydride led either to single liquid (oil) compounds or to white solids. These were identified by NMR as 2,4‐diaddition products 79a / 79b and 80a / 80b , Scheme …”

“…These were identified by NMR as 2,4-diaddition products 79a/79b and 80a/80b, Scheme 24. [25] Scheme 24. Reprinted from ref.…”

“…Reprinted from ref. [25] In the reactions between 1a or 1b and pyridazine (81), the nature of the activation agent gives rise to an important difference with regard to the formation of the corresponding products: when 81 reacts with methyl chloroformate and 1a, δ-lactone 83 is obtained through iodocyclization via an isolable dihydropyridazine 82, whereas the reactions of 81, triflic anhydride, and 1a or 1b directly produce the γ-lactones 84 (Scheme 25). Scheme 25. According to the presented results, other heterocyclic frameworks could be used as logical candidates to extend the range of the compounds capable of being built by the approach of nucleophilic addition of compounds 1.…”

Rearomatization of trifluoromethyl sulfonyl dihydropyridines: Thermolysis vs photolysis

“…Taking advantage of the pyridine activation versatility, ours and other research groups have described the direct synthesis of functionalized polycyclic δ‐ and γ‐lactones via a double nucleophilic addition of bis(trimethylsilyl)ketene acetals to previously activated pyridines. Recently, it has been shown that this reaction can be extended to other aza‐aromatic substrates such as pyrazine, quinoxaline, and pyrimidine, where the course of the reaction depends on the activating agent . We also reported that this method could be applied to pyridine N oxide, affording tetrahydrofuro[3,2‐ b ]pyridine‐2(3 H )‐ones through a double‐activation procedure and an unexpected decarboxylation step .…”