Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 127, Issue 36, Pages 12566-12576Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja052362i
Keywords
-
Categories
Ask authors/readers for more resources
In this article we performed an extensive density functional [BP86/6-311 ++G(3df,3pd) level] investigation of the hypersurface of the Mitsunobu reaction. Reaction of a phosphine with a dialkyl azodicarboxylate (first step in the Mitsunobu conversion) leads to either a five-membered oxadiazaphosphole ring (more stable) or a betaine. The subsequent formation of two stable intermediates, a dialkoxyphosphorane and an acyloxyalkoxyphosphorane, constitutes the second step in the mechanism. These intermediates are in equilibrium with each other (under exchange of alkoxy and acyloxy ligands), and both can undergo an acid-induced decomposition to yield the alkoxy- and/or acyloxyphosphonium salts. The alkoxyphosphonium salt generates the desired ester via a S(N)2 mechanism (inversion product), Alternatively, the phosphorus atom in a mixed acyloxyalkoxyphosphorane species can easily undergo Berry pseudorotation. A subsequent intramolecular substitution leads to the final ester via a retention mechanism. The hypersurface is much more complicated than previously assumed, and the Mitsunobu reaction is fundamentally capable of running under either inversion or retention. The possibility of selective stereocontrol is discussed. Side reactions include the formation of a degradation product and an anhydride.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available