Reductions with diimide

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Diimide reduction is a chemical reaction that converts unsaturated organic compounds to reduced alkane products. In the process, diimide (H2N2) is oxidized to elemental nitrogen.[1]

Introduction

In 1929, the conversion of oleic acid to stearic acid in the presence of hydrazine was observed. Diimide was not implicated in this reductive process until the 1960s. Since that time, several methods of generating transient amounts of diimide have been developed. In the presence of unpolarized alkenes, alkynes or allenes, transient diimide is converted into elemental nitrogen with reduction of the unsaturated functionality. Diimide formation is the rate-limiting step of the process, and a concerted mechanism involving cis-diimide has been proposed. This reduction represents a metal-free alternative to catalytic hydrogenation reductions, and does not lead to the cleavage of sensitive O–O and N–O bonds.

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Mechanism and Stereochemistry

Prevailing Mechanism

Diimide reductions result in the syn addition of hydrogen to alkenes and alkynes. This observation has led to the proposal that the mechanism involves concerted hydrogen transfer from cis-diimide to the substrate. The cis isomer is the less stable of the two; however, acid catalysis may speed up equilibration of the trans and cis isomers.[2]

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Diimide is typically generated either through the oxidation of hydrazine or the decarboxylation of potassium diazocarboxylate. Kinetic experiments suggest that regardless of its method of generation, the formation of diimide is rate-limiting. The transition state of the hydrogen transfer step is likely early; however, high stereoselectivity has been obtained in many reductions of chiral alkenes.[3]

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The order of reactivity of unsaturated substrates is: alkynes, allenes > terminal or strained alkenes > substituted alkenes. Trans alkenes react more rapidly than cis alkenes in general. The reactivity difference between alkynes and alkenes is usually not great enough to isolate intermediate alkenes; however, alkenes can be isolated from allene reductions.

Scope and Limitations

Diimide is most effective at reducing unpolarized carbon-carbon double or triple bonds. Many groups ordinarily sensitive to reductive conditions, including peroxides, are not affected by the conditions of diimide reductions.[4]

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Diimide will selectively reduce less substituted double bonds under some conditions.

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Allenes are reduced to the more highly substituted alkene in the presence of diimide, although yields are low.[5]

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Iodoalkynes represent an exception to the rule that alkenes cannot be obtained from alkynes. After diimide reduction of iodoalkynes, cis-iodoalkenes may be isolated.

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Recently, diimide has been generated catalytically through the oxidation of hydrazine by a flavin-based organocatalyst. This system selectively reduces terminal double bonds.[6]

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A limited number of examples of reduction of polarized double bonds exist in the literature. Aromatic aldehydes are reduced by diimide generated through the decarboxylation of potassium azodicarboxylate.[7]

Comparison with Other Methods

Reductions of carbon-carbon double and triple bonds are most commonly accomplished through catalytic hydrogenation. Diimide reduction offers the advantages that the handling of gaseous hydrogen is unnecessary and removal of catalysts and byproducts (one of which is gaseous elemental nitrogen) is straightforward. Hydrogenolysis side reactions do not occur during diimide reductions, and N–O and O–O bonds are not affected by the reaction conditions. On the other hand, diimide reductions often require long reaction times, and reductions of highly substituted or polarized double bonds are sluggish.

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Experimental Conditions and Procedure

Typical Conditions

A variety of methods for the generation of diimide exist. The most synthetically useful methods are:

  • Oxidation of hydrazine with oxygen, in the presence of catalytic copper(II) and/or a carboxylic acid
  • Decarboxylation of dipotassium diazocarboxylate in the presence of an acid
  • Thermal decomposition of sulfonylhydrazides

Procedures (particularly those employing air as an oxidant) are typically straightforward and do not require special handling techniques.

Example Procedure[8]

Acetic acid-O-d (1.2 g) was slowly added dropwise into a solution of the carboxylic acid 8 (200 mg, 1 mmol) and dipotassium azodicarboxylate (400 mg, 2.5 mmol) in DMSO (7 mL). After stirring 4 hours at room temperature the solution was diluted with brine and extracted with pentane. The pentane layer was dried and evaporated to afford 160 mg (75%) of 5-exo-6-exo-dideuterio-3-endo-phenylsulfinylbicyclo[2.2.1]heptane-2-endo-carboxylic acid (9): mp 183–184°. 1H NMR (DMSO-d6): δ 7.32 (s, 5H) 4.37 (m, 1H), 4.17 (m, 1H), 3.68 (m, 1H), 3.48 (m, 1H), 2.60 (m, 2H), 1.49 (br s, 2H).

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References

  1. Pasto, D.J.; Taylor, R.T. Org. React. 1991, 40, 91.
  2. L. G. Spears, Jr. and J. S. Hutchinson, J. Chem. Phys., 88, 240 (1988).
  3. E. J. Corey, D. J. Pasto, and W. L. Mock, J. Am. Chem. Soc., 83, 2957 (1961).
  4. W. Adam and H. J. Eggelte, J. Org. Chem., 42, 3987 (1977).
  5. K. Mori, M. Ohki, A. Sato, and M. Matsui, Tetrahedron, 28, 3739 (1972).
  6. Smit, C.; Fraaije, M.; Minnaard, A. J. Org. Chem. 2008, 73, 9482.
  7. D. C. Curry, B. C. Uff, and N. D. Ward, J. Chem. Soc. C, 1967, 1120.
  8. R. Annunziata, R. Fornasier, and F. Montanari, J. Org. Chem., 39, 3195 (1974).