Halides free-radical reduction

The present work reports such an approach with the synthesis of (vinyl)polystyrene polyHIPEs and their functionalisation by free radical addition of thiols to the remaining unsaturations. The interest of such materials is proven by the presentation of an application of a thiol functional support in free radical reduction of alkyl halides. 

In a second time, the reduction of an unsaturated halide was an interesting goal because such a reaction could be an easy access to cyclic molecules via a radical cyclisation in competition with the hydrogen transfer. 6-bromohex-l-ene is one of the compound whose free radical reduction was the most extensively studied, according to the radical clock status of the 6-hex-1-enyl radical11. Therefore, it appeared of interest to study it with the above system. The results obtained are reported in table 2. 

During the period 1996-2000 the use of BusSnH, Ph3SnH or Me3SnH in simple free-radical reduction chemistry of halides was reported on numerous occasions "... 

To decide between these two models, they compared rate-structure profiles for the disappearance of alkyl halides in contact with magnesium with rate-structure profiles for others models of reduction. These included (1) rate-structure profiles for the free radical reduction of alkyl chlorides with tri-M-butyltin hydride in diethyl ether [33], assuming... 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

Tri-rc-butylstannane is able to reductively replace halogen by hydrogen. Mechanistic studies indicate a free radical chain mechanism.199 The order of reactivity for the halides is RI > RBr > RC1 > RF, which reflects the relative ease of the halogen atom abstraction.200... 

Although the tin hydride reductions of alkyl halides seem simple, one must be careful because these reactions occur by a free radical mechanism. This is important, because the carbon radical produced in the reaction can isomerize68,78 and one often obtains two different stereoisomers from the synthesis. Another problem is that chiral centres can be lost in tin hydride reductions when an optically active halide is reduced. One example of this is the reduction of benzyl-6-isocyanopenicillanate with tributyltin deuteride78 (Scheme 14). The amount of isomerization depends on the temperature, the concentration of the tin hydride and the presence of and /-substituents78-82. However, some authors have reported tin hydride reductions where no racemization was observed78. 

The dehalogenation of organic halides by organotin hydrides takes place in most cases with a free-radical mechanism [1, 84, 85], The stereospecific reduction of 1,1-dibromo-l-alkenes with Bu3SnH discovered by Uenishi and coworkers [86-89], however, did not occur in the absence of palladium complexes and did not involve radicals. For the synthesis of (Z)-l-bromo-l-alkenes, [(PPh3)4Pd] proved to be the most effective catalyst which could also be generated in situ. The reaction in Eq. (7) proceeded at room temperature and a wide range of solvents could be used. 

The reduction of trialkyltin halides by PMHS is catalyzed by aqueous KF and can be used in situ for free radical- or palladium-catalyzed reactions of the stannanes, and this protocol probably provides the best way of... 

Results of a chemical activation induced by ultrasound have been reported by Nakamura et al. in the initiation of radical chain reactions with tin radicals [59]. When an aerated solution of R3SnH and an olefin is sonicated at low temperatures (0 to 10 °C), hydroxystannation of the double bond occurs and not the conventional hydrostannation achieved under silent conditions (Scheme 3.10). This point evidences the differences between radical sonochemistry and the classical free radical chemistry. The result was interpreted on the basis of the generation of tin and peroxy radicals in the region of hot cavities, which then undergo synthetic reactions in the bulk liquid phase. These findings also enable the sonochemical synthesis of alkyl hydroperoxides by aerobic reductive oxygenation of alkyl halides [60], and the aerobic catalytic conversion of alkyl halides into alcohols by trialkyltin halides [61]. 

There has been some exploration of the mechanism of reduction of d transition metal complexes by M2+(aq) (M = Eu, Yb, Sm). Both inner- and outer-sphere mechanisms are believed to operate. Thus the ready reduction of [Co(en)3]3+ by Eu2+(aq) is necessarily outer-sphere. 2 However, the strong rate dependence on the nature of X when [Co(NH3)5X]2+ or [Cr(H20)5X]2+ (X = F, Cl, Br or I) are reduced by Eu2+(aq) possibly suggests an inner-sphere mechanism.653 The more vigorous reducing agent Yb2+ reacts with [Co(NH3)6]3+ and [Co(en)3]3+ by an outer-sphere route but with [Cr(H20)5X]2+ (X = halide) by the inner-sphere mechanism.654 Outer-sphere redox reactions are catalyzed by electron-transfer catalysts such as derivatives of isonicotinic acid, one of the most efficient of which is iV-phenyl-methylisonicotinate, as the free radical intermediate does not suffer attenuation through disproportionation. Using this catalyst, the outer-sphere reaction between Eu2+(aq) and [Co(py)(NH3)5]3+ proceeds as in reactions (18) and (19). Values found were ki = 5.8 x KFM-1 s 1 and k kx = 16.655... 

J. Dsroszewski, J. Lusztyk, M. Degueil, C. Navarro, and B. Maillard, FleptamelhyItrisiIane-2-thiol-mediated free-radical-chain reduction of organic halides, J. Chem. Soc. Chem. Commun. p. 586 (1991). 

Besides new insight into the reactivity of free radicals, methods for die production of carbon-centered free radicals have also seen major improvements in die last several years. One very common new mediod is to use tin-based reagents as radical chain carriers. Trialkyltin radicals readily abstract bromine or iodine from carbon to produce a carbon-centered free radical. Placement of a bromide or iodide substituent on a substrate dius permits formation of a carbon-centered free radical at diat position using tin-based mediodology. This process was initially developed for die reduction of alkyl halides, and it remains an excellent synthetic method for diat purpose. The complete chain mechanism for die reduction is shown. 

If, oil the other hand, R- is unsaturated and can undergo cyclization rapidly, it will do so. This competition between reduction of the first formed radical R and its cyclization to a new cyclic radical R - is the same as discussed for the formation of free radicals from alkyl halides and tributyltin radicals. The only difference is in the way in which the carbon-centered radical is produced. 

Although less common, ketyl anions can also be generated by removal of an a-hydrogen from an alkoxide (Figure 1, reaction 3). An interesting example where a ketyl anion is formed as an intermediate in this manner is provided by the electrochemically-initiated reduction of an aryl halide by an alkoxide anion via the free radical chain process illustrated in Scheme l6. 

Radical reductions of alkyl halides in water.1 Radical reactions with Bu3SnH are limited to organic solvents, but this tin hydride (1) is sufficiently soluble in water to reduce alkyl bromides or iodides under free-radical conditions in water or in organic solvents. 

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