Page 190 - Advanced Organic Chemistry Part B - Reactions & Synthesis

162 When a hindered ketone is to be converted to a methylene derivative, the best
results are obtained if potassium t-alkoxide is used as the base in a hydrocarbon solvent.
CHAPTER 2 243
Under these conditions the reaction can be carried out at elevated temperatures.
Reactions of Carbon Entries 10 and 11 illustrate this procedure.
Nucleophiles with
Carbonyl Compounds The reaction of nonstabilized ylides with aldehydes can be induced to yield
E-alkenes with high stereoselectivity by a procedure known as the Schlosser modifi-
cation of the Wittig reaction. 244 In this procedure, the ylide is generated as a lithium
halide complex and allowed to react with an aldehyde at low temperature, presumably
forming a mixture of diastereomeric betaine-lithium halide complexes. At the temper-
ature at which the addition is carried out, there is no fragmentation to an alkene and
triphenylphosphine oxide. This complex is then treated with an equivalent of strong
base such as phenyllithium to form a -oxido ylide. Addition of one equivalent of
t-butyl alcohol protonates the -oxido ylide stereoselectivity to give the syn-betaine as
a lithium halide complex. Warming the solution causes the syn-betaine-lithium halide
complex to give trans-alkene by a syn elimination.

Li – +
H O Li R′
RCH CHR′ RCH CR′ R′ H
PhLi t-BuOH
R
+
+
+
+
Li O – P Ph 3 Li O – P Ph 3 H P Ph 3 R H
+
An extension of this method can be used to prepare allylic alcohols. Instead of
being protonated, the -oxido ylide is allowed to react with formaldehyde. The -oxido
ylide and formaldehyde react to give, on warming, an allylic alcohol. Entry 12 is an
example of this reaction. The reaction is valuable for the stereoselective synthesis of
Z-allylic alcohols from aldehydes. 245

O – O –
+ 1) CH 2 O R CH 2 OH
RCHCH PPh 3 RLi RCHC PPh 3
R′ –25°C R′ 2) 25°C H R′
betaine β-oxido ylide

The Wittig reaction can be applied to various functionalized ylides. 246
Methoxymethylene and phenoxymethylene ylides lead to vinyl ethers, which can be
hydrolyzed to aldehydes. 247

243 J. M. Conia and J. C. Limasset, Bull. Soc. Chim. France, 1936 (1967); J. Provin, F. Leyendecker, and
J. M. Conia, Tetrahedron Lett., 4053 (1975); S. R. Schow and T. C. Morris, J. Org. Chem., 44, 3760
(1979).
244
M. Schlosser and K.-F. Christmann, Liebigs Ann. Chem., 708, 1 (1967); M. Schlosser, K.-F. Christmann,
and A. Piskala, Chem. Ber., 103, 2814 (1970).
245
E. J. Corey and H. Yamamoto, J. Am. Chem. Soc., 92, 226 (1970); E. J. Corey, H. Yamamoto,
D. K. Herron, and K. Achiwa, J. Am. Chem. Soc., 92, 6635 (1970); E. J. Corey and H. Yamamoto,
J. Am. Chem. Soc., 92, 6636 (1970); E. J. Corey and H. Yamamoto, J. Am. Chem. Soc., 92, 6637 (1970);
E. J. Corey, J. I. Shulman, and H. Yamamoto, Tetrahedron Lett., 447 (1970).
246 S. Warren, Chem. Ind. (London), 824 (1980).
247
S. G. Levine, J. Am. Chem. Soc., 80, 6150 (1958); G. Wittig, W. Boll, and K. H. Kruck, Chem. Ber.,
95, 2514 (1962).