Formal Substitution of Bromocyclopropanes with Nitrogen Nucleophiles

Abstract

A highly chemo- and diastereoselective protocol toward amino-substituted donor-acceptor cyclopropanes via the formal nucleophilic displacement in bromocyclopropanes is described. A wide range of N-nucleophiles, including carboxamides, sulfonamides, azoles, and anilines, can be efficiently employed in this transformation, providing expeditious access to stereochemically defined and densely functionalized cyclopropylamine derivatives.

Construction of 2-Pyrone Skeleton via Domino Sequence between 2-Acyl-1-Chlorocyclopropanecarboxylate and Amines

“…Therefore, Cs 2 CO 3 as the most appropriate 5 base was chosen to study the effect of solvent, base loading and reaction temperature.…”

“…When R 1 is an aryl group, the reaction of substrates 1a-1i proceeded smoothly to afford the corresponding 2-pyrones 3aa-3ia in moderate to (Table 2, entries 1-9), depending upon the electronic property of substituent groups on aromatic ring. In fact, electron-donating groups such as MeO and Me favored the formation of products 3ba and 3ca in excellent yields (Table 2, entries 2-3), whereas electron-withdrawing groups like Cl and Br decreased the yields of products 3da, 3ea and 3fa in comparison with 3aa (Table 2, entries [4][5][6]. Substrates 1g-1i with biphenyl, 2-thienyl or 1-naphthyl groups were also tolerated in this process, affording products 3ga-3ia in moderate to good yields, respectively (Table 2, entries 7-9).…”

“…To our delight, the relative yields of 3bb to 4b were somewhat elevated when 1 equiv. of each of the metal alkoxides was added (Table 4, entries [3][4][5]. Especially, addition of Al(OPr-i) 3 almost caused the disappearance of 4b, and the isolated yield of 3bb was raised to 63% (Table 4, entry 5).…”

Chiral methyl trans-2,2-dichloro-3-methylcyclopropanecarboxylate upon exposure to thiophenolate nucleophile

“…[16][17][18][19][20] Recently, numerous examples of stereoselective substitution in monobromocyclopropanes with heteroatomic nucleophiles have been described. 21,22 In continuation of our research, 10,11 the substitution of halogens by thiophenoxy groups in the chiral acids 1 has become the object of investigation. The stereochemistry of the dithiocyclopropanes obtained and the process of the cyclopropane ring opening were studied.…”

One-pot synthesis of GABA amides via the nucleophilic addition of amines to 3,3-disubstituted cyclopropenes

“…In our studies 9 of donor-acceptor cyclopropanes (DAC), 10 we investigated the possibility to access substituted GABA derivatives 5 via the ring opening of DAC 1 (Scheme 1). The propensity of DACs toward ring cleavage is proportional to polarization of the C–C bond between electron-donating (EDG) and electron-withdrawing (EWG) groups.…”