Other Hydrogen-Transfer Reagents

CHAPTER 5 REDUCTION OF CARBONYL AND OTHER FUNCTIONAL GROUPS 

Catalytic hydrogenation transfers the elements of molecular hydrogen through a series of complexes and intermediates. Diimide, HN=NH, an unstable hydrogen donor that can only be generated in situ, finds some specialized application in the reduction of carbon-carbon double bonds. Simple alkenes are reduced efficiently by diimide, but other easily reduced functional groups, such as nitro and cyano, are unaffected. The mechanism of the reaction is pictured as a transfer of hydrogen via a nonpolar cyclic transition state. 

In agreement with this mechanism is the fact that the stereochemistry of addition is syn.22 The rate of reaction with diimide is influenced by torsional and angle strain in the alkene. More strained double bonds react more rapidly.23 24 For example, the more strained trans double bond is selectively reduced in Z,/f-1,5-cyclodccadicnc. 

Hartung and R. Simonoff, Org. React. 7, 263 (1953) P. N. Rylander, Catalytic Hydrogenation over Platinum Metals, Academic Press, New York, 1967, Chapter 25 P. N. Rylander, Catalytic Hudrogenation in Organic Synthesis, Academic Press, New York, 1979, Chapter 15 P. N. Rylander, Hydrogenation Methods, Academic Press, Orlando, Florida, 1985, Chapter 13. 

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While hydrogenation using metal hydrides and other hydrogen transfer reagents offers a feasible method for laboratory experimentations, activation of molecular hydrogen with metal or metal organic catalysts is broadly employed in industrial hydrogenation processes. 

Other Hydrogen-Transfer Reagents Group III Hydride-Donor Reagents... 

The reaction of allenes with peracids and other oxygen transfer reagents such as dimethyldioxirane (DM DO) or hydrogen peroxide proceeds via allene oxide intermediates (Scheme 17.17). The allene oxide moiety is a versatile functionality. It encompasses the structural features of an epoxide, an olefin and an enol ether. These reactive intermediates may then isomerize to cyclopropanones, react with nucleophiles to give functionalized ketones or participate in a second epoxidation reaction to give spirodioxides, which can react further with a nucleophile to give hydroxy ketones. 

Hydrogen-transfer Reagent in Radical Reactions. Thiols, in particular tertiary mercaptans such as tert-butanethiol and triethylmethanethiol, have been widely used in radical reactions to trap radical intermediates by hydrogen atom transfer. ferf-Dodecanethiol is a vahd substitute for those mercaptans, since it is cheap, relatively odorless compared to the other alkanethiols, and generally equally efficient with respect to the hydrogen donor properties. 

Coenzymes serve as recyclable shuttles—or group transfer reagents—that transport many substrates from their point of generation to their point of utilization. Association with the coenzyme also stabilizes substrates such as hydrogen atoms or hydride ions that are unstable in the aqueous environment of the cell. Other chemical moieties transported by coenzymes include methyl groups (folates), acyl groups (coenzyme A), and oligosaccharides (dolichol). 

Characterization of ion structures by bimolecular reactions, in which an ion is allowed to react with a neutral gas of known structure and the ionic products are analysed by mass spectrometry, depends on isomeric species having distinctive reactivities which reflect the functional group(s) that are present. This method is conceptually analogous to the use of structure-specific test reagents in classical solution chemistry. Sometimes a group may be transferred to a particular ion from the gas (methylene transfer is commonly encountered) on other occasions, hydrogen transfer is monitored. The latter is conveniently combined with isotopic labelling. 

The success of such reactions depends on the intramolecular hydrogen transfer being faster than hydrogen-atom abstraction from the stannane reagent. In the example show, this is favored by the thermodynamic driving force of radical stabilization, by the intramolecular nature of the hydrogen transfer, and by the steric effects of the central quaternary carbon. This substitution pattern often favors intramolecular reactions as a result of conformational effects. Scheme 10.12 gives some other examples of tandem radical reactions. 

Modern variations include the in situ, and thus catalytic, use of this high-valent selective reagent, not only for alcohols but also for ethers (see later). Ru(VII) (perruthenate) in the compounds tetra-n-butylammonium perruthenate (TBAP) and tetra-n-propylammonium perruthenate (TPAP) has found wide application in alcohol oxidation. Ru-oxo complexes with valence states of IV to VI are key intermediates in, for example, the selective oxygen transfer to alkenes, leading to epoxides. On the other hand 16-electron Ru(II) complexes can be used to catalyse hydrogen transfer thus these are excellent catalysts for oxidative dehydrogenation of alcohols. A separate section is included to describe the different mechanisms in more detail. 

There is no doubt that free-radical chemistry has benefited enormously through the invention of tin-based chain-carrying reagents " . Of these, tributyltin hydride and, to a lesser extent, triphenyltin hydride have been the reagents of choice. Their ready availability and favourable rate constants for attack of the corresponding tin-centred radicals at a variety of radical precursors , coupled with useful rate constants for hydrogen transfer to aUtyl and other radicals, provide for reagents superior to their silicon counterparts only tris(trimethylsilyl)silane rivals tributyltin hydride in its synthetic utility . 

Visible light irradiation of l,2-dihydro-2-thioxo-l-pyridinyl jV-(4-alkenyl)-A-alkylcarbamates (PTOC carbamates) produces substituted pyrrolidines by a radical chain reaction (see Section 7.2.5.1). In the absence of hydrogen donors, the intermediate pyrrolidinylmethyl radical reacts with the PTOC carbamate itself to afford 2-[(2-pyridinylthio)methyl]pyrrolidines, e.g., 1, 2, 4 and 521,22. On the other hand, in the presence of a good transfer reagent, another functionality can be introduced. In the presence of diphenyl diselenide, the phenylseleno-sub-stituted products were obtained in good yield, e.g., 3 and 622. In every case, however, a low degree of diastereoselectivity of the cyclization products is observed. 

The manner in which ethyl Grignard reagents (and many other metal alkyls with hydrogen atoms attached to their P-carbon atoms) can function as reducing agents by alkene elimination and P-hydrogen transfer probably also involves hypercarbon species [Eq. (1.5)]. Similar hypercarbon species appear... 

There have been many approaches published to "immobilize" a homogeneous catalyst. These heterogeneous catalysts must have better activity, selectivity, lifetime or some other property to warrant their use in an industrial chemical process. This talk will draw upon the author s experiences at DuPont and Air Products with Nation , Nafion on carbon, anionic attached [Rh(CO)2l2] to Reillex-425, carbons as catalysts for the hydrolysis of esters, heterogeneous catalyst to activate dimethyl ether as a methyl transfer reagent, and monoliths as hydrogenation catalysts. These individual experiences will show the complexities of a simple problem - "immobilization". 

The synthetic utility of stannane-based reagents is discussed in other chapters of this compilation. While several workers have examined more general types of hydrogen transfer reactions by computational techniques, this chapter will focus on the modeling of hydrogen transfers of synthetic utility, in particular the ability of various modeling methods to accurately predict the stereochemical outcome of free-radical reductions. 

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