Sodium borohydride, lithium aluminum hydride, and sodium bis(methoxyethoxy)aluminum hydride (Vitride) are the most common hydride-reducing agents available for organic chemistry. These super hydrides can be used where high stereoselectivity is required.
Solvent Effects on the Relative Reactivity of the Functional Groups Halide and Tosylate towards Lithium Aluminum Hydride
What is comparatively less recognized is that both the reducing power and the selectivity of reducing agents can be dramatically switched depending on the solvent in which the reduction is performed. So much so that this may be an easier means to achieve a particular selectivity than changing the reagent itself.
S. Krishnamurthy published a note in J. Org. Chem. 1980, 45, 2550-2551 teaching the dramatic effect of solvent choice on the competitive reduction of alkyl halides (chloride, bromide, and iodide followed a similar pattern) in competition with the tosylates of the same hydrocarbon substructure.
As one would predict for any ethereal solvent the reduction with lithium aluminum hydride followed the rate Cl<Br<I and the order of increasing rate with varying solvent was diglyme >monoglyme >THF >ethyl ether.
What was startling to me was that for tosylate the rate of reduction was about the same as bromide but the selectivity of reaction velocity according to solvent was quite the opposite: ethyl ether >THF> monoglyme >diglyme
The practical significance of the difference turns out to be that in a competitive reaction between a tosylate and a halide in the same molecule, one can achieve selective reductive of one or the other group simply by changing the solvent. In diethyl ether, the tosylate will be selectively reduced to hydrocarbon in the presence of the halide while in diglyme the halide will be selectively removed in the presence of the tosylate.
Dr. Krishnamurthy explains this using the theory of tight and solvent-separated ion pairs. He proposes that in diethyl ether the lithium cation is poorly solvated and forms a tight ion pair with the hydride donor which is less nucleophilic towards the halides. But because the tosylate group has its own oxygens these preferentially complex the lithium ion and increase the reactivity of the tetrahydridoaluminate which attacks by a pseudo cyclic transition state with a reactivity more like a solvent-separated anion.
When the solvent becomes increasingly able to solvate the lithium-ion the result is a solvent-separated hydrido aluminate anion whose reactive order is iodide> bromide> tosylate >chloride.
The KiloMentor blog has discussed means to exchange such high boiling solvents as diglyme or monoglyme, making them more practically useful as solvents. It would also be interesting to explore the relative reactivities of halides and tosylates when treated with lithium aluminum hydride in the presence of say bis-trimethylsilylated polyethylene glycol because this polymer can be removed from a reaction mixture by precipitation with either diethyl ether or hexane.
Effect of Lanthanides on the relative reactivity of Carbonyls (aldehydes versus ketones) to reduction
Aldehydes are more easily reduced than other carbonyls, right?
Well usually, but the selectivity can be reversed dramatically and inexpensively. In a communication in 1979, Jean-Lpuis Luche and Andre Luis Gemal published a communication, J. Am. Chem. Soc. 101(19) 5848 1979, teaching that in reductions by sodium borohydride in ethanol/water of mixtures of carbonyls, or different carbonyls in the same molecule, the addition of one equivalent of a transition metal salt so effectively catalyzed the formation of geminal diol in the case of saturated aldehyde that a ketone would be reduced preferentially. The preferred transition salt was cerium chloride. A 50% excess of sodium borohydride was needed because the metal accelerated the reaction of hydride with solvent as well.
This could be a very desirable outcome. It would be useful to be able to mask a ketone by reduction and then use an aldehyde in the same molecule as a reactant in some other transformation where it is reactive but in the presence of the ketone would produce unwanted by-products.
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