Halides as leaving groups

In most Sn2 reactions, halides routinely serve as convenient and readily available leaving groups. They are easily formed from alcohols under a variety of conditions. Because the application of these reactions to sugars is a major component of this chapter, a complete discussion of halogenation reactions will be presented in Section 6.4. 

---

Displacement of a metal-coordinated halide by a metal carbonyl anion is a good method for forming a bond between the two metals. This method is related to redox condensation, differing only in having the halide as leaving group, instead of carbon monoxide. 

Instead of halides as leaving groups, Hendrickson used triflinate (-SO2CF3) as the leaving group to carry out the Ramberg-BScklund reaction (the Hendrickson modification). For instance, treatment of sulfonyl-triflinate 63 with -BuLi provided cyclohexene 64 in 70% yield.43... 

Such rate difference as there is for attack on (86) depends on the ability of X, through electron-withdrawal, to influence the relative ease of attack on the substrate by the nucleophile it is in the reverse order of the relative ability of the halide ions as leaving groups. When the same series of halides is reacted with C HsNHMe (in nitrobenzene at 120°), however, the relative rates for X = F, Cl and Br were found to be 1, 15 and 46, e.g. in the order of their relative ability as leaving groups, so that in this latter reaction it would appear that step (2) is now involved, to some extent at least, in the rate-limiting step overall. 

In alkyl halides the leaving group is the halogen substituent — it leaves as a halide ion. 

I would like to bring up a couple of points here because I think Basolo and Baddley s experiment of blocking the fifth and sixth positions is a very good one. I would like to ask them if they would do the experiment, if they have not done it, in which chloride, bromide, and iodide are replaced as leaving groups to see if the order reverses to give the octahedral halide leaving order, rather than the planar one in which iodide is slower than chloride. This would help firm up this case. 

Aryl- and heteroaryl halides can undergo thermal or transition metal catalyzed substitution reactions with amines. These reactions proceed on insoluble supports under conditions similar to those used in solution. Not only halides, but also thiolates [76], nitro groups [76], sulfinates [77,78], and alcoholates [79] can serve as leaving groups for aromatic nucleophilic substitution. 

The extent of this failure is evident from comparisons of experimental measurements of rate and equilibrium constants. One comparison in the literature is provided by Ritchie and coworkers study of the relatively stable cation, pyronin (the 3,6-bis(dimethylamino)xanthylium cation 71) with a series of nucleophiles.252 Another example is McClelland s measurements of rate and equilibrium constants for the reactions of halide and acetate ions with the trityl cation.19 As already mentioned fluoride and acetate are less reactive than bromide and chloride despite their equilibrium affinities being much greater. This is reflected indeed in the much lower rates of solvolysis of the fluoride and acetate than bromide or chloride as leaving groups... 

For electrophiles such as Me3SiCH2X strong ground-state destabilization has been observed for X = 4-nitrobenzoate[130]. For X= halide, on the other hand, this ground-state destabilization is significantly smaller, and it may therefore be advisable to choose carboxylates or sulfonates as leaving groups when alkylations with a-silyl-substituted electrophiles are to be performed. 

---