Radicals, coupling reactions with alkyl halides

The reactions of alkyl halides with Fe(II) deuteroporphyrin IX have been examined (Wade and Castro 1973). Three classes of reaction were observed (i) hydrogenolysis, (ii) elimination to alkenes, and (iii) coupling of alkyl free radicals. Further discussion has been given in Castro (1998). 

The reaction of thiyl radicals with silicon hydrides (Reaction 3.18) is the key step of the so called polarity-reversal catalysis in the radical-chain reduction of alkyl halides as well as in the hydrosilylation of olefins using silane-thiol couple (see Sections 4.5 and 5.1) [33]. The reaction is strongly endothermic and reversible (Reaction —3.18). 

As stated above, intermolecular coupling reactions between carbon atoms are of limited use. In the classical Wurtz reaction two identical primary alkyl iodide molecules are reduced by sodium. n-Hectane (C100H202), for example, has been made by this method in 60% yield (G. Stallberg, 1956). The unsymmetrical coupling of two alkyl halides can be achieved via dialkylcuprates. The first halide, which may have a branched carbon chain, is lithiated and allowed to react with copper(I) salts. The resulting dialkylcuprate can then be coupled with alkyl or aryl iodides or bromides. Although the reaction probably involves radicals it is quite stereoselective and leads to inversion of chiral halides. For example, lithium diphenyl-cuprate reacts with (R)-2-bromobutane with 90% stereoselectivity to form (S)-2-phenylbutane (G.M. Whitesides, 1969). 

Radical addition/cross-coupling products 61 were obtained in 60-91% yield when Ni(dppf)Cl2 was applied as a catalyst in reactions of alkyl halides 60 with 2,3-disubstituted dienes 59 and aryl Grignard or arylzinc reagents (Fig. 12). Competition experiments of n-, sec-, and ferf-butyl bromide with 2,3-dimethylbutadiene... 

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],... 

Lipshutz and colleagues presented recently palladium-catalyzed direct coupling reactions of alkyl iodides and vinyl bromides or iodides catalyzed by 1 mol% Pd(amphos)Cl2 in the presence of zinc and TMEDA in a biphasic aqueous/poly-(ethylene glycol tocopheryl sebacate) reaction medium [198], Internal olefins were obtained in 51-95% yield. For aryl-substituted (Aj-vinyl bromides, retention of double bond geometry was observed, while different degrees of isomerization occurred for (Z)-isomers, which may indicate the intervention of a radical addition process in the course of the coupling process. Alkyl-substituted (Z)-vinyl halides were transformed in contrast with retention of alkene geometry. Aryl halides also reacted [199],... 

With an E° value of —0.75 V, entry no. 19 of Table 17, reaction between alkyl halides and alkyllithium compounds, represents a strongly exergonic electron-transfer reaction which is expected to proceed at a diffusion-controlled tate. Experimental rate constants are not available, but such reactions are qualitatively known to be very fast. As we proceed to entry no. 21, two model cases of the nucleophilic displacement mechanism, it can first be noted that the nosylate/[nosylate]- couple is electrochemically reversible the radical anion can be generated cathodically and is easily detected by esr spectroscopy (Maki and Geske, 1961). Hence its E° = —0.61 V is a reasonably accurate value. E° (PhS /PhS-) is known with considerably less accuracy since it refers to an electrochemically irreversible process (Dessy et al., 1966). The calculated rate constant is therefore subject to considerable uncertainty and it cannot at present be decided whether the Marcus theory is compatible with this type of electron-transfer step. In the absence of quantitative experimental data, the same applies to entry no. 22 of Table 17. For the PhS-/BuBr reaction we again suffer from the inaccuracy of E° (PhS /PhS-) what can be concluded is that for an electron-transfer step to be feasible the higher E° value (—0.74 V) should be the preferred one. The reality of an electron-transfer mechanism has certainly been strongly disputed, however (Kornblum, 1975). 

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