Diastereoselectivity controlled by electrostatic repulsion between the negative charge on a trifluoromethyl group and that on aromatic ringsElectronic supplementary information (ESI) available: general experimental methods and typical reaction procedure. See http://www.rsc.org/suppdata/cc/b1/b105602f/

Abstract

Intramolecular electrostatic repulsions between the local negative charge on a trifluoromethyl group and that on the ortho position of an aryl moiety of a nucleophile was found to be a controlling factor of the diastereoselectivity in a cyclopropanation reaction, in which the electrostatic repulsion was evaluated quantitatively.

The Effects of Ring Substituents and Leaving Groups on the Kinetics of SNAr Reactions of 1‐Halogeno‐ and 1‐Phenoxy‐nitrobenzenes with Aliphatic Amines in Acetonitrile

“…This may be attributed to the large “steric” effect of the ortho ‐CF 3 group 6,9. There is evidence12,13 that this is not simply a size effect but results partly from electrostatic repulsion between the local negative charge on the CF 3 group and bulky nucleophiles. Our results show that this effect still operates in 6b where there is an ortho ‐CF 3 group but no other ortho substituent.…”

Effects of ortho‐ and para‐Ring Activation on the Kinetics of SNAr Reactions of 1‐Chloro‐2‐nitro‐ and 1‐Phenoxy‐2‐nitrobenzenes with Aliphatic Amines in Acetonitrile

“…The steric effects of the CF 3 group in nucleophilic substitutions have been noted previously, [20] and its size has been estimated to be comparable to that of an isopropyl group. [28] Recent calculations [29] have shown that these effects may derive in part from electrostatic repulsions between the local negative charge on the trifluoromethyl group and the incoming nucleophile. Although the X-ray structure of 4b does not indicate any particularly large effects in the parent molecule the kinetic results suggest that sterically the effect of an ortho-CF 3 group on nucleophilic attack is greater than that of a nitro group.…”

1,1,1-Trifluoro-2,3-epoxypropane

“…Intermolecular interaction caused by the negative charge on the trifluoromethyl group resembles that caused by the π electrons on a phenyl group. 33 Thus, the ring-opening products of TFPO with amines would be alternatives of β-amino-α-phenethylalcohols. Of course, the β-amino-α-phenethylalcohol provides the basic skeleton of α/β-agonists or antagonists, such as epinephrine sympathomimetics.…”

“…44, 46 This diastereoselectivity was explained by the Coulombic repulsion between the negative charge on the trifluoromethyl group and that on π-system of aromatic rings. 33 The trifluoromethylated cyclopropanes were transformed to cyclopropane amino acids (eq 28). 47 A trialkylaluminum as a Lewis acid catalyst promotes ringopening reaction of the TFPO with a variety of carbon nucleophiles (eq 30).…”