DEAD/DIAD - More than Simple Mitsunobu Reagents

Introduction

Diethyl azodicarboxylate (DEAD) and diisopropyl azodicarboxylate (DIAD) (Figure  [¹] ), are widely used reagents in organic synthesis.

Figure 1

These are important reagents in the Mitsunobu reaction, [¹] [²] which is a versatile and widely used method for the dehydrative coupling of an alcohol with clean stereogenic inversion and is perhaps the most favorable reaction to invert chiral centers of secondary alcohols. [¹] [²] This kind of reaction can also be applied in aminations, cyclodehydrations, deoxygenations, and in dehydrative alkyl­ations. [³]

Besides the direct association of DEAD/DIAD with the Mitsunobu reaction, [²] there are many other reactions in which these reagents can be applied. For example, DEAD/DIAD are efficient components in Diels-Alder reactions and in click chemistry, [4a] they function as dienophiles in some cycloadditions, [4b] and they can be used in the synthesis of functionalized β-amino alcohols from aldehydes and ketones. [4c] DEAD and DIAD are commercially available or can be prepared in the laboratory in a two-step synthesis from hydrazine, first by condensation with ethyl chloroformate followed by treatment of the resulting ethyl hydrazodicarboxylate with chlorine or fuming nitric acid (Scheme  [¹] ). [5]

Scheme 1

References

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