A Thermodynamic Preference of Chiral N-Methanesulfonyl and N-Arenesulfonyl 2,3-cis-3-Alkyl-2-Vinylaziridines over Their 2,3-Trans-Isomers:  Useful Palladium(0)-Catalyzed Equilibration Reactions for the Synthesis of (E)-Alkene Dipeptide Isosteres

Abstract

Palladium(0)-catalyzed reactions of N-methanesulfonyl- or N-(arenesulfonyl)-3-alkyl-2-vinylaziridines reveal that 2,3-cis-isomers are more stable than the corresponding 2,3-trans-isomers in accord with ab initio calculations. A highly stereoselective synthetic route to (E)-alkene dipeptide isosteres having desired stereochemistries from 2,3-cis-3-isobutyl-2-vinylaziridine by the use of organocopper chemistry is also presented.

Stereodivergent Synthesis of Chiral 2-Alkenylaziridines: Palladium(0)-Catalyzed 2,3-cis-Selective Aziridination and Base-Mediated 2,3-trans-Selective Aziridination

“…As shown in Table 1, methyl carbonates 12c-e also gave the corresponding 2,3-cis-aziridines 14c-e in extremely high diastereoselectivities by treatment with a catalytic amount of Pd(PPh 3 ) 4 under equilibrated conditions (entries 3-5). 20,21) Interestingly, the methyl carbonates 12f and 12g having a tert-butyl group also gave the corresponding sterically highly congested 2,3-cis-aziridines 14f and 14g as the major products. Apparently, the relatively low 2,3-cis selectivities (87 : 13-91 : 9) would be attributed to the unfavorable steric interaction between the tert-butyl group and the alkenyl group.…”

“…[2][3][4][5][6][7][8] Particularly, aziridines bearing an alkenyl [9][10][11][12][13][14] or ethynyl group [15][16][17][18] on one of the aziridine-ring carbon atoms have proven to be extremely useful intermediates for asymmetric preparation of such compounds as alkaloids, 9,10) b-lactams, 11-13) vinylglycines, 14) amino allenes, 15,16) amino alcohols, 17,18) and (E)-alkene dipeptide isosteres. [19][20][21][22] Although some stereoselective syntheses of enantiomerically pure 2-alkenylaziridines have been reported, most of the reported methods consist of two processes, formation of the aziridine ring and construction of the olefinic moiety, via several steps.In connection with our program directed toward synthesis of (E)-alkene dipeptide isosteres, [19][20][21] we required an efficient stereoselective synthetic method of chiral 2-alkenylaziridines. Recently, we reported a palladium(0)-catalyzed aziridination of allylic carbonates 1a preferentially affording thermodynamically more stable 2,3-cis-2-vinylaziridines 2 over the corresponding trans isomers 3 in good selectivities (2 : 3ϭ94 : 6-98 : 2, Eq.…”

“…20,21) In contrast, base-mediated intramolecular amination of mesylates 1b with NaH in DMF produces mixtures of 2 and 3 in variable ratios (2,3-cis : transϭ8 : 92-51 : 49) depending on the steric bulkiness of the alkyl substituent R 1 (Eq. 2).…”

“…In connection with our program directed toward synthesis of (E)-alkene dipeptide isosteres, [19][20][21] we required an efficient stereoselective synthetic method of chiral 2-alkenylaziridines. Recently, we reported a palladium(0)-catalyzed aziridination of allylic carbonates 1a preferentially affording thermodynamically more stable 2,3-cis-2-vinylaziridines 2 over the corresponding trans isomers 3 in good selectivities (2 : 3ϭ94 : 6-98 : 2, Eq.…”

“…23) In these reaction conditions, the palladium catalyst not only converts the carbonates 1a into the aziridines 2 and 3 but also equilibrates the isomeric mixtures of 2 and 3 via p-allylpalladium(II) intermediates A. 20,21) In contrast, base-mediated intramolecular amination of mesylates 1b with NaH in DMF produces mixtures of 2 and 3 in variable ratios (2,3-cis : transϭ8 : 92-51 : 49) depending on the steric bulkiness of the alkyl substituent R 1 (Eq. 2).…”