Lewis Acid-Promoted Cyclization Reactions of Alkenyl Ethenetricarboxylates: Stereoselective Synthesis of 2-Oxotetrahydrofurans and 2-Oxopyrrolidines

Abstract

Lewis acid-promoted intramolecular reactions of alkenyl ethenetricarboxylates and the corresponding amides have been examined. Reaction of allyl ethenetricarboxylates and the amides with Lewis acids (1-2 equiv) such as TiCl4, TiBr4, AlCl3, and AlBr3 gave 3,4-trans-halogenomethyl 2-oxotetrahydrofuran and pyrrolidine derivatives stereoselectively in high yields. The stereochemistries were determined by NOE experiments. Reaction of alkyl-substituted allylic ethenetricarboxylates with Lewis acids gave chloro 2-oxotetrahydrofurans and pyrans. For some alkyl-substituted substrates, cationic intermediates may be formed under the reaction conditions, and rearranged products have been obtained.

Six‐Membered Ring Formation from Lewis Acid Promoted Reactions of 2‐Substituted 2‐Alkenyl Amides and Esters of Ethenetricarboxylate

“…In addition, the concerted dyotropic rearrangement TS for the transition B′ to D′ (Y = NMe) could also be calculated 13. However, the pathway has a very high activation energy (Δ G ‡ = 59.07 [43.55 kcal/mol]), similar to that of the oxygen analogue5a (Scheme ). The large differences between the activation energy of the ring extension relative to B (Y = O, 24.06 [15.40] kcal/mol; Y = NMe, 20.03 [9.62] kcal/mol) and that of TS(dyo) relative to B′ (Y = O, 61.39 [48.61] kcal/mol; Y = NMe, 59.07 [43.55] kcal/mol) can be explained as follows.…”

“…Relative Gibbs free energies ( T = 298.15 K and P = 1 atm) for the intermediates and TSs of the model compounds ( 1m + Al 2 Cl 6 ) and ( 3m + Al 2 Cl 6 ) were obtained at the B3LYP/6‐31G* (without brackets) and B3LYP/6‐311+G(d,p) SCRF = (PCM, solvent = CH 2 Cl 2 )//B3LYP/6‐31G* (in square brackets) levels of theory. The values for A , TS1 , B , TS2 , C , TS3 , and D for Y = O (without brackets) were taken from previous work 5a. The energy diagram displaying all the energies of A , TS1 , B , TS2 , C , TS3 , and D (Y = O, NMe) relative to the compound A is shown in Figure 1.…”

“…The mechanism proposed for the oxygen analogue in previous work5a has been adopted (Scheme ). Some other possible mechanisms have also been examined.…”

“… Concerted dyotropic pathway for the transition of B′ to D′ . IRC calculations of the TS(dyo) s led to six‐membered‐ring intermediates D′ (Y = NMe) and D′d (Y = O), which is a slightly unstable conformational isomer of D′ (Y = O) in Scheme 5a. The Gibbs free energies ( T = 298.15 K, P = 1 atm) calculated at the B3LYP/6‐31G* and B3LYP/6‐311+G(d,p) SCRF = (PCM, solvent = CH 2 Cl 2 )//B3LYP/6‐31G* levels are given relative to 1m + AlCl 3 (Y = O) and 3m + AlCl 3 (Y = NMe), respectively.…”

“…The Lewis acid promoted reactions of these substrates gave five‐membered rings in most cases. However, interestingly, we observed the formation of a six‐membered ring from the 2‐methylpropenyl ester of ethenetricarboxylate [ 1 ; Equation (2)] 5a …”