Convenient protocols for Mizoroki–Heck reactions of aromatic bromides and polybromides with fluorous alkenes of the formula H₂CCH(CF₂)_n−1CF₃ (n = 8, 10)

Abstract

The fluorous alkenes HC[double bond, length as m-dash]CHR (R = (CF)CF; n = 8, 10) undergo the Mizoroki-Heck reaction with a variety of aromatic monobromides and polybromides such as 1,3- and 1,4-CHBr, 1,3,5-CHBr, 1,3,5-CHBrCl, 1,4-XCHBr (X = CF, R, COCH, CN, 1,4-OCHBr), 1,2-ONCHBr, 5-bromoisoquinoline, 5-bromopyrimidine, 3-bromo-5-methoxypyridine, and 3,5-dibromopyridine (sixteen examples, 78% average isolated yield). Typically, 1.2-2.4 equiv. of alkene are employed per Ar-Br bond, together with Pd(OAc) catalyst (4-5 mol%/Ar-Br bond), n-BuN Br (0.8-1.0 equiv./Ar-Br bond), NaOAc (1.2-2.4 equiv./Ar-Br bond), and 3 : 1 w/w DMF/THF as solvent (120 °C). No effort is necessary to exclude air or moisture, and reactions may be conducted on >10 g scales. Only E isomers of the products Ar(CH[double bond, length as m-dash]CHR) are detected. Thirteen representative examples are hydrogenated (Pd/C, balloon pressure H), giving Ar(CHCHR) (92% average isolated yield).

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity

“…As shown in Scheme 1 , related fluorous aryliodine(III) dichlorides with three-methylene spacers, (R f8 CH 2 CH 2 CH 2 ) 2 C 6 H 3 ICl 2 , had been isolated (the isomers III , IV ) [ 17 ]. Recently, a potential precursor with two-methylene spacers, 1,3-(R f8 CH 2 CH 2 ) 2 C 6 H 4 , became readily available [ 49 ]. Accordingly, it could be iodinated with I 2 /H 5 IO 6 as shown in Scheme 6 (bottom) to give 1,2,4-(R f8 CH 2 CH 2 ) 2 C 6 H 3 I [ 50 ] in 93% yield after work-up.…”

Revisiting the Heck Reaction for Fluorous Materials Applications

“…Nonetheless, the atom connectivity could be assessed to confirm the successful functionalization and a coplanar orientation of the FAA group with aromatic rings. As a further comparison, we synthesized compound 5 in 86% isolated yield using the microwave and obtained a higher yield than 76%, reported by Su et al 17 Conditions B were also shown to be compatible with the installation of C 6 F 13 chains (compound 6, 42% yield) and to tolerate pyridine groups (compound 7, 31% yield), although the yields with the shorter fluorocarbons were slightly lower than the C 8 F 17 chain analogues. All products are soluble in common organic solvents and could be easily isolated in pure form by silica gel column chromatography.…”

“…Fluoroalkyl alkenes (FAAs) are affordable and accessible precursors, providing an impressive potential of fluorinated material discovery (Figure 1, c). FAAs were first utilized in Pd-catalyzed Heck reactions by Chen and co-workers 14,15 and have been demonstrated to react with aryl halides, [14][15][16][17][18] aryl diazonium salts, 19,20 and aryl boronic acids. 21 However, the substrate scope in these reports was mostly limited to phenyl groups, with a few exceptions including nitrogen-containing heterocycles, 18 naphthyl groups, 20 binaphthyl groups, 14,15,22 and perylene bisimides.…”

Pd-Catalyzed Mizoroki-Heck Reactions Using Fluorine-Containing Agents as the Cross-Coupling Partners

“…Moreover, 77 could be easily separated by F-SPE (Fluorous solid phase extraction) technique and reused three times without significant loss of activity. Gladysz and co-workers reported a convenient and scalable procedure for the cross-couplings of fluorous alkenes (80) with aryl bromides (81) using a modified Jeffery version of the Mizoroki-Heck reaction (Scheme 16) [72]. Fluorous alkenes (80) reacted with aryl monobromides and polybromides (81), such as 1,3-and 1,4-C 6 H 4 Br 2 , 1,3,5-C 6 H 3 Br 3 , 1,3,5-C 6 H 3 Br 2 Cl, 1,4-XC 6 H 4 Br (X = CF 3 , C 8 F 17 , COCH 3 , CN, 1,4-OC 6 H 4 Br), 1,2-O 2 NC 6 H 4 Br, 5-bromo-isoquinoline, 5-bromopyrimidine, 3-bromo-5-methoxypyridine, and 3,5-dibromopyridine, under the modified Mizoroki-Heck coupling conditions to afford the corresponding fluorophilic adducts (82) in good to high yields.…”