Coupling perfluoroalkyl halide

Castle and Widdowson were first to disclose alkyl-alkyl Kumada coupling reactions catalyzed by Pd(dppf)Cl2 [195]. This report was later questioned and corrected by Scott [196]. Matsubara and colleagues established formal Stille-type coupling reactions of perfluoroalkyl halides with allyl, alkynyl, or vinyl stannanes catalyzed by 10 mol% of Pd(PPh3)4, which have to be considered, however, better as radical addition/elimination reactions rather than as coupling reactions (see Sect. 3.1) [184],... 

Because of the radical mechanism for SET reactions, introduction of both a perfluoroalkyl group and a heteroatom moiety to the carbon-carbon double [17-20] and even triple [21] bonds is possible. The initially generated perfluoroalkyl radicals add first to olefins to form a new radical intermediate (23), which then couples with anions (22) to form new anion radicals (24). The formation of the product (25) and the chain propagation via electron transfer from anion radicals (24) to perfluoroalkyl halides constitutes a chain reaction as shown in Scheme 2.38. Sulfur [19], selenium [20], tellurium [21], and phosphorus [22] anions (22) have been employed for these reactions [23]. 

Cross-coupling of perfluoroalkyl halides (Fig. 35) with vinyl and allyl bromides in the presence of zinc occurs in the presence of palladium(O) or (II)... 

Perfluoroalkylcopper compounds, derived from perfluoroalkyl halides and copper in dipolar aprotic solvents such as dimethyl sulfoxide and N,N-dimethylacetamide, are rather stable. These complexes couple effectively with aryl and vinyl halides (Burdon et al., 1967, 1972a McLoughlin and Thrower, 1969). 

Despite the lower reactivity of solvated perfluoroalkylzinc reagents, perfluoroalkyl iodides undergo synthetically useful zinc-mediated reactions under Barbier conditions which often employ ultrasound and co-catalysts. Under these conditions, the zinc reagents are not well characterized and radical intermediates and SET mechanisms are proposed in some cases. Representative examples are presented below and include the ultrasound-promoted, zinc-mediated perfluoroalkylation of various substrates as reported by Ishikawa and coworkers (Scheme 10)123 126. Yields of carbinols could be improved by use of Ti(II) co-catalyst. Ultrasound promoted the coupling of perfluoroalkyl iodides with vinyl and allyl halides in the presence of Pd co-catalysts. 

Castro et al. 44) found that the order of reactivity of various halides in coupling reactions with ethynylcopper compounds in DMF is ArSX, ArX > RCOX ArCHaX, RCH=CHCH2X, ArCOCHaX > RCH= CHX, Alkyl-X. A somewhat different order is observed for the reactivity of some organic halides towards perhaloarylcopper reagents in THF (97, 147) Allyl Aryl > Alkyl and perfluoroaryl, perfluoro-vinyl > aryl > perfluoroalkyl. Acid halides were also far more reactive than aryl iodides in ethereal solvents 146). The ease of halide displacement is I > Br > Cl. 

The perfluoroaikylcopper reagents have found extensive application as perfluoroalkylation reagents Typical examples of perfluoroalkylation of aryl halides have been illustrated in table 6 These perfluoroaikylcopper reagents readily couple with vinyl iodides and vinyl bromides [220, 221, 222] Typical examples of mono- orbisvmylic coupling are shown in equations 148 and 149 When 1-bromo-1 -perfluoroalkylethy lenes were reacted with perfluoroaikylcopper compounds, the expected gew-disubstituted olefin was not formed, but the vic-disubshtuted product was obtained [223] (equation 150)... 

Alkyl iodides " and perfluoroalkyl iodides react with Zn-Cu couples. Use also is made of mixtures of the alkyl iodide and bromide (e.g., a 1 3 ratio of n-BuI n-BuBr gives n-BujZn in high yield). Byproducts, such as alkenes (R—H) and alkanes, RH, can become problems for secondary alkyl halides, RX, and for these care and control of the conditions and workup are vital. Success is possible as shown by yields of 85% for i-PrjZn, and 72% for s-Bu Zn. Tertiary alkyl iodides do not produce organozincs. 

Scheme 2.121 Cross-coupling of perfluoroalkyl copper(l) and aryl halides or perfluoroiodo olefins [52-54], The CF3CU used for the upper two reactions was generated by metathesis of trifluoromethyl cadmium and copper(l) salts.

Organozinc reagents. Zn-Cu couple often shows higher reactivity than zinc dust towards alkyl halides. Thus perfluoroalkylzinc iodides are rapidly formed in the presence of AIBN, and quenching such reagents in situ by DMF gives perfluoroalkyl aldehydes. (Note that Zn-Ag on graphite is well suited for the preparation of aryl-zinc species). ... 

The trifluoromethylation of aryl iodides has been achieved using the reaction with (trifluoromethyl)-trimethoxyborate and a copper(I)/phenanthroline catalyst." A copper chloride/phenanthroline catalyst has also been used together with (TMP2Zn), zinc bis-tetramethylpiperidide, in the reaction of aryl iodides with perfluoroalkyl derivatives to yield arylperfluoroalkanes. The mechanism is thought to involve initial formation of bis(perfluoroalkyl)zinc species followed by rate-limiting transmetalation with copper halide and reaction with the aryl iodide to give the coupled product." ... 

Readily available Ifl-perfluoroalkanes can also be used for radical alkylation. This method employs, for example, thiazolyl iodide and 1/f-perfluoroalkane reagents, DMPU solvent, TMPjZn base, and a copper chloride/phenanthroline catalyst [8]. The reaction mechanism includes deprotonation of IH-perfluoroalkanes with TMPjZn to afford bis(perflnoroalkyl)zinc species. Subsequent transmetalla-tion with copper halide produces a mixture of anionic Cu species that reacts with aryl iodides (including thiazoles), either directly or via a neutral perfluoroalkyl compound, to give the coupling product. 

Ultrasound can give useful improvements in the yield, reaction time, and convenience of organometallic reactions, and these facets of the technique are demonstrated well in its application to the Reformatsky reaction. Yields are improved by up to almost 100 % over the conventional method, and are nerally superior even to those of the trimethyl borate method. Reaction times are reduced by a factor of 5-10, and the need to prepare zinc powder by the active-metal reduction of anhydrous zinc chloride is eliminated. This technique has also been applied to the zinc-mediated dimerization of a,a -dibromo -xylene, although only low yields are obtained, and to the Pd-catalysed zinc coupling of allyl or aryl halides with perfluoroalkyl iodides. ... 

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