The Wittig Reaction allows the preparation of an alkene by the reaction of an aldehyde or ketone with the ylide generated from a phosphonium salt. The geometry of the resulting alkene depends on the reactivity of the ylide. If R is Ph, then the ylide is stabilized and is not as reactive as when R = alkyl. Stabilized ylides give (E)-alkenes whereas non-stabilized ylides lead to (Z)-alkenes (see Wittig-Horner Reaction).
Mechanism of the Wittig Reaction
Addition of the ylide to the carbonyl is postulated to lead first to the zwitterionic intermediate betaine, which would then close to form a four-membered cyclic intermediate, an oxaphosphetane. The existence of the betaine hasn't been fully established, although its intermediacy plays an important role in the Schlosser Modification. Betaines may be stabilized by lithium salts leading to side products; therefore, suitable bases in the Wittig Reaction are for example: NaH, NaOMe, NEt3).
The driving force is the formation of a very stable phosphine oxide:
Reactive ylides give rapid reaction and subsequent rapid ring opening to give the (Z)-alkene:
Recycling the Waste: The Development of a Catalytic Wittig Reaction
C. J. O'Brien, J. L. Tellez, Z. S. Nixon, L. J. Kang, A. L. Carter, S. R. Kunkel, K. C. Przeworski, G. A. Chass, Angew. Chem. Int. Ed., 2008, 48, 6836-6839.
Generation of Phosphoranes Derived from Phosphites. A New Class of Phosphorus Ylides Leading to High E Selectivity with Semi-stabilizing Groups in Wittig Olefinations
V. K. Aggarwal, J. R. Fulton, C. G. Sheldon, J. de Vicente, J. Am. Chem. Soc., 2003, 125, 6034-6035.
Wittig Reactions in Water Media Employing Stabilized Ylides with Aldehydes. Synthesis of α,β-Unsaturated Esters from Mixing Aldehydes, α-Bromoesters, and Ph3P in Aqueous NaHCO3
A. El-Batta, C. Jiang, W. Zhao, R. Anness, A. L. Cooksy, M. Bergdahl, J. Org. Chem., 2007, 72, 5244-5259.
Direct Conversion of N-Methoxy-N-methylamides (Weinreb Amides) to Ketones via a Nonclassical Wittig Reaction
J. A. Murphy, A. G. J. Commeureuc, T. N. Snaddon, T. M. McGuire, T. A. Khan, K. Hisler, M. L. Dewis, R. Carling, Org. Lett., 2005, 7, 1427-1429.
A highly stereoselective tandem Michael addition-Wittig reaction of (3-carboxy-2-oxopropylidene)triphenylphosphorane and α,β-unsaturated aldehydes gives multifunctional 6-carboxycyclohex-2-en-1-ones in excellent diastereo- and enantioselectivities by employing the combined catalysis of a bulky chiral secondary amine, LiClO4, and DABCO.
Y.-k. Liu, C. Ma, K. Jian, T.-Y. Liu, Y.-C. Chen, Org. Lett., 2009, 11, 2848-2851.
Wittig Olefination between Phosphine, Aldehyde, and Allylic Carbonate: A General Method for Stereoselective Synthesis of Trisubstituted 1,3-Dienes with Highly Variable Substituents
R. Zhou, C. Wang, H. Song, Z. He, Org. Lett., 2010, 12, 976-979.
In the presence of ruthenium-based olefin metathesis catalysts and triphenylphosphine, α,β-unsaturated aldehydes can be olefinated with diazoacetates. A tandem transformation of terminal olefins to 1,3-dienoic olefins in a single operation based on olefin cross-metathesis and Wittig olefination has been developed.
R. P. Murelli, M. L. Snapper, Org. Lett., 2007, 9, 1749-1752.