Boron trifluoride-assisted perfluoroalkylation of carbon-nitrogen double bonds

Abstract

In the presence of BFyOEta, (perfluoroalkyl)lithiums generated in situ from the reaction of primary perfluoroalkyl iodides and MeLi-LiBr reacted with imines, azines, and nitrones to afford perfluoroalkylated nitrogen-containing compounds in moderate to good yields. This method was successfully applied to the preparation of a (perfluoroalkyl)glycine and optically active perfluoroalkylated amines.Methodology for introducing the perfluoroalkyl group into organic molecules has recently been developed greatly due to increasing needs for fluorine-containing compounds in a variety of industrial fields. These methods can be conveniently divided into three types: cationic perfluoroalkylation represented by the reactions of Umemoto's FITS ((perfluoroalkyl)phenyliodonium trifluoromethanesulfonates) reagents;1 2 addition of perfluoroalkyl radicals generated from perfluoroalkyl halides,3 perfluoroalkanoyl peroxides,4 or other perfluoroalkyl sources;5 and nucleophilic or coupling reactions of (perfluoroalkyl)metals represented by (perfluoroalkyl)zinc6 and (perfluoroalkyl)copper reagents.7 In the last type of reaction, difficulties are often encountered due to the instability and low reactivity of these metal reagents. Perfluoroalkyl Grignard and lithium reagents react with carbonyl compounds8 such as aldehydes, ketones, and esters, but they fail to react with less polarized functional groups, leading to self-decompo-

New method of preparation of C2F5Li and its reactions with cyclic imines and lactims: Synthesis of α-pentafluoroethyl proline

“…Addition of the pentafluoroethyl group to the imine double bond of compounds 1a-l proceed smoothly to afford the a-pentafluoroethylated heterocycles 2a-l in reasonable yields (Table 1). In contrast to observation of Uno and coworkers [13], the order of addition of the reagents has no influence on yields of the products. Probably, this is due to different nature of the reagent prepared by Li-Br exchange or by metalation of C 2 F 5 H with BuLi.…”

“…We suggested that reaction of pentafluoroethyllithium with these cyclic imines in the presence of a Lewis acid should proceed as an addition to imine C N bond [13,14]. This approach opens up opportunities for the synthesis of 2-pentafluoroethyl substituted pyrrolidines, piperidines and azepanes, which are very interesting building blocks for potentially biologically active compounds.…”

Mild Synthesis of β‐Amino‐α,α‐difluoro Ketones from Acylsilanes and Trifluoromethyltrimethylsilane in a One‐Pot Imino Aldol Reaction

“…[13d] In the fluorinated series Pirkle et al [14] and Uno et al [15] gave similar data for the perfluoalkylated analogues. As already mentioned by Uno et al, for all these compounds, the anti relative configuration of the H 1 and H 3 atoms was accompanied by a shielding of the H 1 atom due to the phenyl group of the phenethyl moiety ( Table 3).…”

“…Acylsilane R [14] C 6 F 13 syn 4.37 [15] anti 4.00 lylated imine 3j in order to evaluate the effect of an heteroatom in the chiral side-chain on the stereoselectivity of the reaction (Scheme 2). Under the standard conditions, the reactions of the difluoroenoxysilanes derived from the acylsilanes 1 and 2 with 3i gave the β-amino ketones 4i (63 % yield, 79:21 diastereomeric ratio) and 5i (73 % yield, 65:35 diastereomeric ratio), respectively.…”

Parabolic Relationship between the Basicity of the Nucleophile and π-Face Selection in Addition of the Substituted Acetylide Ions to Cyclohexanone and Cyclohexanethione

“…The puzzle of the stereochemistry of addition to cyclohexanones is often defined in terms of the reagent's size: small nucleophiles prefer axial attack, the bulky ones prefer equatorial attack. Consequently, there is a tendency to attribute the effects such as the opposite face preferences of n -hexyllithium (75% equatorial)19a and (perfluoro- n -hexyl)lithium (85% axial) 19b to the differences in the steric demand related to the degree of oligomerization. Our calculations suggest, however, that a change in electronegativity of the nucleophile's substitution may be sufficient to reverse its face preference.…”