Synthesis of Azetidine and Pyrrolidine Derivatives through Selenium-Induced Cyclization of Secondary Homoallylamines − A77Se NMR Study

Abstract

Treatment of α-alkyl and α,α-dialkyl homoallylic amines 1 with PhSeX (X = Cl, Br, I), in CH 3 CN containing sodium carbonate produced mixtures of azetidines 2 and pyrrolidines 3. The cyclization also occurred in the absence of Na 2 CO 3 , and the corresponding azetidinium and pyrrolidinium salts 2(HX) and 3(HX) were formed in CDCl 3 or CH 3 CN. The crude reaction mixtures were analysed by 77 Se NMR. Each product − 2, 3, 2(HX), and 3(HX) − was characterized by its 77 Se chemical shift, and the product ratios were determined for each reaction. The ratios of azetidine 2 to pyrrolidine 3 increased not only according to the steric hindrance around the α-carbon,

Stereocontrolled Synthesis of 1,2-Dialkyl-4-halopyrrolidines through PhSeX-Induced Cyclization of Secondary Homoallylamines

“…provided a mixture of (phenylselanylmethyl)azetidines 2 and (phenylselanyl)pyrrolidines 3. [1] When an excess of PhSeX (X = Cl, Br) was used, 4-halopyrrolidines 4 (X = Cl) or 5 (X = Br) were formed and isolated in very good yields. Mono-or dialkyl 4-halopyrrolidines 4 and 5 could also be obtained stereospecifically by SO 2 Cl 2 or Br 2 treatment of 4-…”

“…The corresponding adduct 7(Br) has been characterized by 77 Se NMR. [1] Azetidine cis-2e (R 1 ϭ tBu, R 2 ϭ H) and pyrrolidine cis-3d (R 1 ϭ iPr, R 2 ϭ H) were separately treated with PhSeBr (1.5 equiv.) in MeCN containing Na 2 CO 3 .…”

“…), we observed that selenium-induced cyclizations of 1a (R 1 ϭ R 2 ϭ H) [1] and of 1g؊1k (R 1 , R 2 ϶ H) [2] always resulted in the same 2/3 mixture. In contrast, the α-substituted amines 1b؊1f (R 2 ϭ H), when a large excess of PhSeX (X ϭ Cl, Br) was added at room temp.…”

“…In the same work, [1] we showed that the azetidinium and pyrrolidinium salts 2(HX) and 3(HX) were formed in the ation of 2a(HX) and 3a(HX). [1] Alkaline hydrolysis then afforded the β-halopyrrolidine 4 (X ϭ Cl) or 5 (X ϭ Br) in good yields (Scheme 3, Table 1; method A 2 ).…”

“…[1] Alkaline hydrolysis then afforded the β-halopyrrolidine 4 (X ϭ Cl) or 5 (X ϭ Br) in good yields (Scheme 3, Table 1; method A 2 ). By the same procedure, but without heating, 4a and 5a were prepared from the parent amine 1a.…”