Halogen effect

Numerous chemical reactions have been carried out on ferrocene and its derivatives.317 The molecule behaves as an electron-rich aromatic system, and electrophilic substitution reactions occur readily. Reagents that are relatively strong oxidizing agents, such as the halogens, effect oxidation at iron and destroy the compound. 

Since the (n-Bu)3Sn radical (R ) is nucleophilic (17), a partial negative charge must be produced at the methine carbon whose chlorine is being abstracted. The rate of this abstraction should clearly be enhanced by electron-withdrawing groups on R due to their stabilization of this charge by inductive effects. As observed, the removal of Cl from EW (or W diad) is expected to be more facile than from EVE (or VE diad) as a result of a -halogen effect in the former structure. 

Scheme 4.2 Halogen effect of the copper(l)-catalyzed reaction of propargyl ether 4.

Jeffers. P.M. and Wolfe, N.L. Homogeneous hydrolysis rate constants-Part 11 additions, corrections and halogen effects. Environ. Toxicol. Chem., 15(7) 1066-1070, 1996. 

Furthermore the different halogen effect (Br/Cl) exerted by electron-withdrawing and electron-releasing substituents on the formation of nitriles parallels that observed in oxidative additions (22). The quanti-... 

Catalyst 36 was also used for the enantioselective synthesis of functionalized tetrahydropyrans, important building blocks in several biologically active molecules (Scheme 29) [78]. The enantioselectivity of such a reaction was significantly improved by using a ruthenium iodide complex 37. This halogen effect has been previously observed in the ring-closing metathesis (vide supra) [52]. 

B. Halogen Effect on the Stereochemistry of the Grignard Formation Reaction... 

In his paper dealing with the separation of radical and anion cyclizations Garst also comments on the apparent halogen effects on product distributions in both sodium naphthalenide and sodium mirror reactions 96 While there are other possible explanations, the possibility that alkyl halide radical anions could be intermediates that undergo reactions other than fragmentation to alkyl radicals and halide ions should be kept in mind. ... 

Other options lor the —50 -retention limit pathway have drawbacks, (a) l or a triplet or mixed singlet-triplet version of pathway 1-3-4, it is not be clear why spin factors and intersyslem crossing would operate in the same way for reductions by metals or electrodes ax homogeneous reductions by Naph-. yet the presumed limit is found for these types of reactions, (b) Diffusion control of competing steps 2 and 3 could describe reductions by MNaph and solvated electrons but, again, it is not clear how- this would apply to reductions by metals and electrodes. If this competition were not diffusion controlled, [hen a signilicunt step 2 would introduce halogen effects on the limit. 

If step I were practically reversible, then step 0 would also he eliminated by the absence of a coiKCiilpnlion effect. In addition, if step 6 (reversible or not) wcic a signilicam lactor in determining the extent of retention, halogen effects would be expected, but in fact these are nonexistent to very small In the cases near the proposed retention limit. 

In Grignard reageni formation from l-huln-1 -me(hyl-2.2-diphcnvlc>clopropanes. retention is favored in the opposite order. Cl > Br 1 10.2(). This can be accommodated by invoking pathway 6-7 as well as 1-3-4 and 1-8-7. with the halogen effect favoring I (relative to 6) in the order Cl -Br > I. This is not inconsistent with step 3 being favored (relative to 8) in the order I Hr > Ci... 

Thus, data for reductions of I halo-1-methyl 2.2-diphcnyleyelopropancs appear to conform rationally to a mechanism with competing initial steps I and 6 and competing steps 2 and X subsequent to 1 (Scheme 7.1). More reducing power favors I relative to 6 and 3 relative to X. When the halogen effect is determined by the 3 X competition, retention varies in the older I Ur > Cl > I-. and w hen it is determined by the l-b competition, it varies oppositely. 

Alternatively, pathway 6-7 could always be insignilicanl. If so. the order of the halogen effect on the 3-8 competition would have to be sensitive to conditions. 

Figure 7.29 is a schematic diagram illustrating the diffusion-reaction phenomenon that gives rise to the halogen effect that is observed w ith ordinary... 

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