Page 187 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Phosphonium ylides are usually prepared by deprotonation of phosphonium salts. 159
The phosphonium salts that are used most often are alkyltriphenylphosphonium halides,
which can be prepared by the reaction of triphenylphosphine and an alkyl halide. The SECTION 2.4
alkyl halide must be reactive toward S 2 displacement. Olefination Reactions of
N
Stabilized Carbon
Nucleophiles
+
Ph P + RCH X Ph PCH R X –
2
3
3
2
X = I, Br, or Cl
+– base
Ph PCH R Ph P CHR
2
3
3
Alkyltriphenylphosphonium halides are only weakly acidic, and a strong base must
be used for deprotonation. Possibilities include organolithium reagents, the anion
of dimethyl sulfoxide, and amide ion or substituted amide anions, such as LDA
or NaHMDS. The ylides are not normally isolated, so the reaction is carried out
either with the carbonyl compound present or with it added immediately after ylide
formation. Ylides with nonpolar substituents, e.g., R = H, alkyl, aryl, are quite reactive
toward both ketones and aldehydes. Ylides having an -EWG substituent, such as
alkoxycarbonyl or acyl, are less reactive and are called stabilized ylides.
The stereoselectivity of the Wittig reaction is believed to be the result of steric
effects that develop as the ylide and carbonyl compound approach one another. The
three phenyl substituents on phosphorus impose large steric demands that govern the
formation of the diastereomeric adducts. 240 Reactions of unstabilized phosphoranes are
believed to proceed through an early TS, and steric factors usually make these reactions
selective for the cis-alkene. 241 Ultimately, however, the precise stereoselectivity is
dependent on a number of variables, including reactant structure, the base used for
ylide formation, the presence of other ions, solvent, and temperature. 242
Scheme 2.17 gives some examples of Wittig reactions. Entries 1 to 5 are typical
examples of using ylides without any functional group stabilization. The stereoselec-
tivity depends strongly on both the structure of the ylide and the reaction conditions.
Use of sodium amide or NaHMDS as bases gives higher selectivity for Z-alkenes than
do ylides prepared with alkyllithium reagents as base (see Entries 3 to 6). Benzyli-
denetriphenylphosphorane (Entry 6) gives a mixture of both cis- and trans-stilbene on
reaction with benzaldehyde. The diminished stereoselectivity is attributed to complexes
involving the lithium halide salt that are present when alkyllithium reagents are used
as bases.
-Ketophosphonium salts are considerably more acidic than alkylphosphonium
salts and can be converted to ylides by relatively weak bases. The resulting ylides,
which are stabilized by the carbonyl group, are substantially less reactive than unfunc-
tionalized ylides. More vigorous conditions are required to bring about reactions
with ketones. Stabilized ylides such as (carboethoxymethylidene)triphenylphosphorane
(Entries 8 and 9) react with aldehydes to give exclusively trans double bonds.
240
M. Schlosser, Top. Stereochem., 5, 1 (1970); M. Schlosser and B. Schaub, J. Am. Chem. Soc., 104, 5821
(1982); H. J. Bestmann and O. Vostrowsky, Top. Curr. Chem., 109, 85 (1983); E. Vedejs, T. Fleck,
and S. Hara, J. Org. Chem., 52, 4637 (1987).
241 E. Vedejs, C. F. Marth, and P. Ruggeri, J. Am. Chem. Soc., 110, 3940 (1988); E. Vedejs and C. F.
Marth, J. Am. Chem. Soc., 110, 3948 (1988); E. Vedejs and C. F. Marth, J. Am. Chem. Soc., 112, 3905
(1990).
242
A. B. Reitz, S. O. Nortey, A. D. Jordan, Jr., M. S. Mutter, and B. E. Maryanoff, J. Org. Chem., 51, 3302
(1986); B. E. Maryanoff and A. B. Reitz, Chem. Rev., 89, 863 (1989); E. Vedejs and M. J. Peterson,
Adv. Carbanion Chem., 2, 1 (1996); E. Vedejs and M. J. Peterson, Top. Stereochem., 21, 1 (1994).