Thermal Decomposition of Stereoisomeric 3-Aroyl- and 3-Carbomethoxyaziridines in Acetonitrile

Abstract

The thermal decomposition of I-alkyl-3-benzoyl-2-(m-nitrophenyl)aziridines in dry acetonitrile results in a series of autocatalytic hydrolytic cleavages, 1,3-dipolar additions, condensations, and rearrangements to give products including oxazolidines, 1,2-dihydropyrazines, pyrrolo-[3,4-4-4-oxazolines, and a-aminoketones.The marked differences in product type and distribution from cis-and trans-aziridines are ascribed to preferential hydrolytic opening at the aziridinium ion stage. Complete equilibration of the stereoisomeric azomethine ylides takes place prior to 1,3-dipolar additions.Thermal decomposition of cis-and trans-methyl I-isopropyl-2-(m-nitrophenyl)aziridine-3-carboxyates in acetonitrile is not autocatalytic (and can be suppressed) and produces three stereoisomeric oxazolidines in identical yields and ratios, and methyl N-isopropylglycine by selective hydrolytic attack at the 2-aziridine position. This result is ascribed to equilibration of the stereoisomeric aziridines prior to hydrolytic cleavage by adventitious moisture only.La decomposition thermique des alkyl-l benzoyl-3 m-nitrophknyl-2 aziridines dans I'acttonitrile sec conduit a une strie de clivages hydrolytiques autocatalysts, d'additions dipolaires-1,3, de condensations et de rearrangements donnant des produits comprenant des oxazolidines, des dihydro-1,2 pyrazines, des pyrroles[3,4-dl oxazolines-4 et des a-aminodtones. Les differences notables dans le type de produit et leur distribution A partir des aziridines cis et trans sont attribuees a I'ouverture prkferentielle par hydrolyse au stade de I'ion aziridinium. L'kquilibration compltte des ylures azomkthine stertoisomtres se fait avant les additions dipolaires-1,3. La decomposition thermique des carboxylates d'isopropyl-l m-nitrophknyl-2 aziridine-3 de mkthyle cis et trans, n'est pas autocatalytique (et peut &re supprimke) et conduit trois oxazolidines stireoisomtres dans des rapports et des rendements identiques et a la mtthyl-N-isopropylglycine par hydrolyse selective sur la position-2 de I'aziridine. Ce resultat est attribue a I'tquilibration des aziridines st6reoisomtres avant clivage par hydrolyse causte seulement par une humiditt accidentelle.

1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides with Carbonyl Dipolarophiles Yielding Oxazolidine Derivatives

“…A marked difference in reactivity was observed for the corresponding trans-aziridine isomer, which underwent mainly hydrolytic ring-cleavage processes, and only small amounts of each oxazolidine were isolated. In contrast, both cis-and trans-3-carbomethoxyaziridines 33 formed the corresponding stereoisomeric oxazolidines 34 and 35 in identical ratios and yields by an analogous partial hydrolytic fragmentation/cycloaddition process (Scheme 6) [58]. The thermolysis of an N-unsubstituted aziridine, dimethyl 3-[(4-nitro)phenyl]aziridine-2,2-dicarboxylate, in toluene also lead to an oxazolidine, albeit in low yield, from a partial fragmentation/cycloaddition process [59].…”

One‐Pot Stereoselective Synthesis of 2‐Acylaziridines and 2‐Acylpyrrolidines from N‐(Propargylic)hydroxylamines

“…15, H 6.62, N 5.96. 3, 26.2, 26.4, 26.5, 29.5, 30.0, 36.1, 47.2, 47.3, 52.2, 65.4, 69.2, 127.5, 128.3, 128.56, 128.65, 129.2, 133.1, 134.8, 137.8, 178.0, 179.0, 198.2 ppm;IR (KBr): ñ = 2922, 2851, 1769, 1697, 1593, 1432, 1381, 1337, 1277, 1230, 1189, 1131, 1094, 1048 ; elemental analysis calcd (%) for C 27 H 30 N 2 O 3 : C 75.32, H 7.02, N 6.51; found: C 75.26, H 7.11, N 6.53. Crystal data: C 27 H 30 N 2 O 3 ; M r = 430.55; monoclinic; space group P2 1 /c; a = 8.4348 (7), b = 21.818(2), c = 12.635(1) ; V = 2231.4(3) 3 ; b = 106.338(2)8; Z = 4; D calcd = 1.281 g cm À3 ; R = 0.051 (R w = 0.066) for 3690 reflections with I > 3.00s(I) and 289 variable parameters.…”

“…[2] The general methods for the preparation of 2-acylaziridines include the metal-catalyzed addition of nitrenes to alkenes, [3] the metal-catalyzed addition of carbenes to imines, [4] the Michael-addition/elimination of hydroxylamine and hydrazine derivatives to enones, [5] the ringclosure of 2-azido-3-hydroxy ketones, [6] and the nucleophilic addition of amines to a,b-dibromoketones. [7] Although trans-2-acylaziridines can be readily prepared, the stereoselective synthesis of cis-2-acylaziridines is rather difficult and only a few methods for the preparation of cis-3-alkyl-substituted 2-acylaziridines have been reported. [4a,b,d] The Baldwin rearrangement of 4-isoxazolines is known to afford 2-acylaziridines; however, the reaction conditions are drastic and the diastereoselectivity is not always good.…”

Further Synthetic Applications of Functionalized 1,3-Dipoles

“…Oppolzer's method of preparation allows the introduction of a functional group on the nitrogen end of the dipolar species, whereas nitrile imines are necessarily available only with the functional group on the carbon end (12). Two azomethine imines, derived from hydrazides and formaldehyde were investigated, [3]. The dipolar species lOtr R, = CH,.…”