Wittig Reaction-百灵威

The Wittig reaction uses triphenylphosphine (PPh₃), a base, and a 1° or 2° alkyl halide to convert an aldehyde or ketone to an olefin. First a phosphonium salt is made when the PPh₃ attacks the alkyl halide, releasing a halide ion in the process. The α-hydrogen is then deprotonated by the base, creating a phosphorus ylide, which attacks the aldehyde or ketone, forming a cis or trans betaine intermediate. Rearrangement of the resulting oxaphosphetane produces the final E/Z olefin product.

Lab Tips:

Phosphorus ylides selectively react with aldehydes and ketones, leaving esters and amides intact. ^[1]
Care must be taken when handling the ylide as it is water and oxygen-sensitive. ^[1]
E-or Z-selectivity is influenced by the type of ylide (stabilized, semi-stabilized, nonstabilized), steric effects that develop as the ylide and carbonyl compound approach each other, and the nature of the solvent and base. ^[1,2]
Stabilized and nonstabilized ylides tend to provide greater stereoselectivity than semi-stabilized ylides. Under salt-free/dipolar aprotic conditions with aldehydes for instance, stabilized ylides give predominantly (E)-olefins, nonstabilized ylides afford olefins with high (Z)-selectivity, while semi-stabilized ylides usually afford a more even mixture. ^[1,2]
Tetrasubstituted alkenes cannot be prepared because of steric hindrance. ^[3]
Carrying out this reaction on a solid support allows easy separation of the products from triphenylphosphine oxide. ^[1].

_{1. Kürti, L., Czakó, B. (2005). Strategic Applications of Named Reactions in Organic Synthesis; Background and Detailed Mechanisms. Burlington, MA: Elsevier Academic Press.
2. Carey, F.A., Sundberg, R.J. (2001). Advanced Organic Chemistry Part B: Reactions and Synthesis (4th ed.). New York: Kluwer Academic/Plenum Publishers.
3. McMurry, J. (2000). Organic Chemistry (5th ed.). Pacific Grove, CA: Brooks/Cole.}

Reagents: Triaryl- or trialkylphosphine, Base (RLi, NaH, NaOR, etc.), Solvent (THF, Et₂O, DME, MTEB, or toluene)
Reactant: 1° or 2° Alkyl Halide (Cl, Br, I, OTs), Aldehyde or Ketone
Product: Olefin
Type of Reaction: Nucleophilic Addition of Phosphorus Ylides
Bond Formation: C=C