Free Radical Addition of HBr: Anti-Markovnikov Regiochemistry

Name ______________________________________ Text section 21.7 provides an example of a "dehalogenation" — a reaction that replaces a halogen with a hydrogen by a free radical chain mechanism. The H comes from tributyltin hydride, Bu3Sn–H. 1 Write the propagation steps involved in the reduction of bromocyclopentane to cyclopentane with tributyltin hydride. The initiation steps that produce the chain-carrying Bu3Sn• radical are given; just start with that to write your chain propagation steps. tBuO–OtBu Br + Bu3Sn—H h! tBuO–OtBu init: + Bu3Sn—Br h! tBuO• + H—SnBu3 2 tBuO• tBuOH + •SnBu3 prop: 2 What products would you expect from the following tin hydride reductions? Think about the structure of the intermediate radical, and pay attention to stereochemistry where relevant. O tBuO–OtBu Br + Bu3Sn—H Br h! tBuO–OtBu + Bu3Sn—H h! Lecture outline Free radical addition of HBr goes with "anti-Markovnikov" regiochemistry, e.g., HBr Br peroxide h! or " This rxn goes via a free radical chain mechanism — Init Prop: How does this mechanism account for the anti-Markovnikov regiochemistry? In practice, this rxn is often inadvertently initiated by small amounts of peroxide contaminants that form by autooxidation of certain solvents, esp. ethers. This reaction only works with HBr, not with HCl, not with HI — why? Use BDE values (below) to estimate the ∆H°s for the propagation steps. What do these imply about the Eas for the additions of HBr, HCl, and HI? Remember, all these acids can all react via the "normal" ionic mechanism (via a carbocation), so it's a race between the normal addition and the free-radical addition. Once it gets started, the free radical chain mechanism wins the race in the HBr addition, but the ionic rxn wins with HI and HCl. BDEs (kcal/mol) H–Cl H–Br H–I C–Cl C–Br C–I CC π 103 88 71 84 70 55 65 It's important to realize that the reversal of the normal regiochemistry is unique to the HBr addition (and a few other reactions — see below). One cannot, in general, add a radical initiator and light (or heat) and get a reaction to give the opposite regiochem. Here are a few other examples of additions to π-bonds that go via radical chain mechanisms — peroxide + RS—H Ph + Cl3C–Br SR h! peroxide Ph CCl3 h! Br This can also happen intramolecularly. A classic example is cyclization of the 5-hexenyl radical. k = 2.3 x 105 sec–1 (! = 4.3 µs) And the reverse process is more favorable when the ring is very strained, as in the opening of the cyclopropylcarbinyl radical. k = 9.4 x 107 sec–1 (! = 11 ns) Additions to π-bonds can also initiate polymerization... R R=H R R polyethylene R = CH3 polypropylene R = Ph polystyrene R = Cl polyvinylchloride R = OAc polyvinylacetate F2C R CF2 CO2CH3 R R polytetrafluoroethylene (Teflon) polymethylmethacrylate (Plexiglass) CH3 polyisoprene (rubber) Another common reaction involving free radicals is Autooxidation — init: prop: X• (or perhaps O2?) + H–R ——> X–H + •R R• + O2 ——> R—O–O• + H–R R—O–O• ——> R–O–O–H + •R Ethers are especially susceptible to autooxidation. Et2O and THF (below) need to be treated with respect in the lab because a build-up of the peroxides that result from their autooxidation can cause explosions. As a precaution, ethers are tested regularly for the presence of peroxides. O O2 O OOH "init" Autooxidation of polyunsaturated fats occurs readily — This is involved in the spoilage of food, drying of oil-based paints, and (perhaps) aging. O yadda yadda O O blah blah blah O O O O2 ultimately leads to aldehydes, ketones, carboxylic acids (The structures above are incomplete!!! Fill in the missing bits...) Free radical chain inhibitors ("anti-oxidants") like BHA and BHT shut down free radical chains — (add the missing bits and complete the structures!) O H R• or ROO• O eventually ... O + R• (or ROO•) BHT "Natural" antioxidants... Vitamin E (a-tocopherol) vitamin C (ascorbic acid) OH HO HO O HO O O OH