Several modifications to the original reagent combination have been developed in order to simplify the separation of the product and avoid production of so much chemical waste. One variation of the Mitsunobu reaction uses resin-bound triphenylphosphine and uses di-tert-butylazodicarboxylate instead of DEAD. The oxidized triphenylphosphine resin can be removed by filtration, and the di-tert-butylazodicarboxylate byproduct is removed by treatment with trifluoroacetic acid. Bruce H. Lipshutz has developed an alternative to DEAD, di-(4-chlorobenzyl)azodicarboxylate (DCAD) where the hydrazine by-product can be easily removed by filtration and recycled back to DCAD.
