Hydrogen-Atom Donors

Reduction by hydrogen-atom donors necessarily involves intermediates with unpaired electrons. Tri-n -butyltin hydride is the most important example of this type of reducing agent. It is able to reductively replace halogen by hydrogen in many types of halogen compounds. Mechanistic studies have indicated a free-radical chain mechanism. The ability of trisubstituted stannanes to function effectively in these 

The reductive dehalogenation can also be applied to the conversion of acid chlorides to aldehydes. A competing reaction leading to conversion of some of the 

Tri- -butyltin hydride shows substantial selectivity toward polyhalogenated compounds, permitting partial dehalogenation. The reason for the greater reactivity of 

CHAPTERS REDUCTION OF CARBONYL AND OTHER FUNCTIONAL GROUPS 

Tri- -butyltin hydride also serves as a hydrogen-atom donor in radical-mediated methods for reductive deoxygenation of alcohols.The alcohol is converted to a thiocarbonyl derivative. These thioesters undergo a radical reaction with tri- -butyltin hydride. 

Because of the expense, toxicity, and purification problems associated with use of stoichiometric amounts of tin hydrides, there has been interest in finding other hydrogen-atom donors. The trialkylboron-oxygen system for radical initiation has been used with tris(trimethylsily)silane or diphenylsilane as a hydrogen-donor system. 

which reflects the relative ease of the halogen atom abstraction. 

A procedure which is catalytic in BuaSnH and uses NaBH4 as the stoichiometric reagent has been developed. This procedure has advantages in the isolation and purification of product. 

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In mbber production, the thiol acts as a chain transfer agent, in which it functions as a hydrogen atom donor to one mbber chain, effectively finishing chain growth for that polymer chain. The sulfur-based radical then either terminates with another radical species or initiates another chain. The thiol is used up in this process. The length of the mbber polymer chain is a function of the thiol concentration. The higher the concentration, the shorter the mbber chain and the softer the mbber. An array of thiols have subsequendy been utilized in the production of many different polymers. Some of these apphcations are as foUow ... 

For the acetoxy radical, the for decarboxylation is about 6.5 kcal/mol and the rate is about 10 s at 60°C and 10 s at —80°C. Thus, only very rapid reactions can compete with decarboxylation. As would be expected because of the lower stability of aryl radicals, the rates of decarboxylation of aroyloxy radicals are slower. The rate for p-methoxybenzoyloxy radical has been determined to be 3 x 10 s near room temperature. Hydrogen donation by very reactive hydrogen-atom donors such as triethylsilane can compete with decarboxylation at moderate temperatures. 

The intermediate diphenylhydroxymethyl radical has been detected after generation by flash photolysis. Photolysis of benzophenone in benzene solution containing potential hydrogen donors results in the formation of two intermediates that are detectable, and their rates of decay have been measured. One intermediate is the PhjCOH radical. It disappears by combination with another radical in a second-order process. A much shorter-lived species disappears with first-order kinetics in the presence of excess amounts of various hydrogen donors. The pseudo-first-order rate constants vary with the structure of the donor with 2,2-diphenylethanol, for example, k = 2 x 10 s . The rate is much less with poorer hydrogen-atom donors. The rapidly reacting intermediate is the triplet excited state of benzophenone. 

If the reaction just described is conducted in the presence of a suitable hydrogen atom donor such as tri-n-butyltin hydride or tert-butyl hydrosulfide, reductive decarboxylation occurs via a radical chain mechanism to give an alkane (see 125—>128, Scheme 24). Carboxylic acids can thus be decarboxylated through the intermediacy of their corresponding thiohydroxamate esters in two easily executed steps. In this reducjtive process, one carbon atom, the carbonyl carbon, is smoothly excised... 

Benzoin and a wide variety of related compounds (e.g. 12, 70-74) have been extensively studied both as initiators of polymerization and in terms of their general photochemistry.271 2 3 The acetophenone chromophore absorbs in the near UV (300-400 nm). In the absence of hydrogen atom donors the mechanism of... 

Novi and coworkers124 have shown that the reaction of 2,3-bis(phenylsulfonyl)-l,4-dimethylbenzene with sodium benzenethiolate in dimethyl sulfoxide yields a mixture of substitution, cyclization and reduction products when subjected at room temperature to photostimulation by a sunlamp. These authors proposed a double chain mechanism (Scheme 17) to explain the observed products. This mechanism is supported by a set of carefully designed experiments125. The addition of PhSH, a good hydrogen atom donor, increases the percent of reduction products. When the substitution process can effectively compete with the two other processes, the increase in the relative yield of substitution (e.g., with five molar equivalents of benzenethiolate) parallels the decrease in those of both cyclization and reduction products. This suggests a common intermediate leading to the three different products. This intermediate could either be the radical anion formed by electron transfer to 2,3-bis(phenylsulfonyl)-l,4-dimethylbenzene or the a radical formed... 

R2P(0)H) and phosphonates (R02P(0)H) as hydrogen atom donors and the corresponding phosphonyl radicals as chain carriers (Scheme 3). 

Reduction Reactions Involving Hydrogen Atom Donors... 

Reduction by hydrogen atom donors involves free radical intermediates and usually proceeds by chain mechanisms. Tri-n-butylstannane is the most prominent example of this type of reducing agent. Other synthetically useful hydrogen atom donors include hypophosphorous acid, dialkyl phosphites, and tris-(trimethylsilyl)silane. The processes that have found most synthetic application are reductive replacement of halogen and various types of thiono esters. 

Hypophosphorous acid has been used as a hydrogen atom donor in the dehalogenation of nucleosides.202... 

Scheme 5.9 illustrates some of the conditions that have been developed for the reductive deoxygenation of alcohols. Entries 1 to 4 illustrate the most commonly used methods for generation of thiono esters and their reduction by tri-M-butylstannane. These include formation of thiono carbonates (Entry 1), xanthates (Entry 2), and thiono imidazolides (Entries 3 and 4). Entry 5 is an example of use of dimethyl phosphite as the hydrogen donor. Entry 6 uses r .s-(trimethylsilyl)silane as the hydrogen atom donor. 

Another alternative for conversion of diols to alkenes is the use of the Barton radical fragmentation conditions (see Section 5.5) with a silane hydrogen atom donor.299... 

The photoadditions proceed through 1,4-diradical intermediates. Trapping experiments with hydrogen atom donors indicate that the initial bond formation can take place at either the a- or (3-carbon of the enone. The excited enone has its highest nucleophilic character at the (3-carbon. The initial bond formation occurs at the (3-carbon for electron-poor alkenes but at the a-carbon for electron-rich alkenes.191 Selectivity is low for alkenes without strong donor or acceptor substituents.192 The final product ratio also reflects the rate and efficiency of ring closure relative to fragmentation of the biradical.193... 

Among the most useful radical fragmentation reactions from a synthetic point of view are decarboxylations and fragmentations of alkoxyl radicals. The use of (V-hydroxy-2-thiopyridine esters for decarboxylation is quite general. Several procedures and reagents are available for preparation of the esters,353 and the reaction conditions are compatible with many functional groups.354 f-Butyl mercaptan and thiophenol can serve as hydrogen atom donors. 

Esters of (V-hydroxyphthalimide can also be used for decarboxylation. Photolysis in the presence of an electron donor and a hydrogen atom donor leads to decarboxylation. Carboxyl radicals are formed by one-electron reduction of the phthalimide ring. 

Similar reactions can be conducted using /ra-(trimethylsilyl)silanc as the hydrogen atom donor.363... 

An alternative method for reductive dediazonation involves in situ diazotization by an alkyl nitrite in dimethylformamide.96 This reduction is a chain reaction with the solvent acting as the hydrogen atom donor. 

Hydrogen bonding means sharing a hydrogen atom between one atom that has a hydrogen atom (donor) and another atom that has a lone pair of electrons (acceptor) ... 

The (3-metaloxy radical was first exploited for synthetic purposes in C—H and C—C bond-forming reactions by Nugent and RajanBabu through the use of titanocene(III) chloride as an electron-transfer reagent [5]. They established that the (3-titaniumoxy radicals formed after electron transfer can be reduced by hydrogen atom donors, e. g. 1,4-cy-clohexadiene or tert-butyl thiol, that they add to a,(3-unsaturated carbonyl compounds, and that they can react intramolecularly with olefins in 5-exo cyclizations. 

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