RESEARCH
Soviet Chemists Modify Wittig Reaction Stereospecific reaction helps in synthesis of higher unsaturated fatty acids; aldehydes and phosphoranes are starting material A group of Moscow chemists have devised a new way to synthesize higher unsaturated fatty acids of the type cisCH 3 (CH 2 ) m C H = C H (CH 2 ) n C O O H. They use as starting materials an aldehyde and w-carbalkoxyphosphoranes in a modification of the Wittig reaction. Professor M. M. Shemyakin, director of the Institute for Chemistry of Natural Products, U.S.S.R. Academy of Sciences, and his co-workers Dr. L. D. Bergelson and V. A. Vaver, also claim that the modification can produce: • Other cis unsaturated acids of the ds-c/s-divinylmethane type, such as linoleic and linolenic. • d.s-ds-Divinylethane acids such as are found in various fish oils. • Triethylenic systems from transtrans-cis, or cis-trans-cis acids. The
first example of such eleostearic acid.
prepared
is
Stereospecific Wittig. Conformational analysis of the Wittig reaction shows that the stereochemical course of the reaction depends on the way in which the initial carbon-carbon bond is formed. Thus it is affected by the dipole-dipole interaction of the reactants and by the relative size of the substituents. If dipole-dipole interaction is an important feature, the reaction will follow a course favoring the trans olefin because of the steric effect of the alkyl group. The Wittig reaction usually yields a mixture of cis and trans oriented products, an excess of the trans form being favored stereochemically. It's now possible to direct the reaction toward a cis oriented product by modifying the environmental con-
ditions, Prof. Shemyakin told the International Symposium on Organic Chemistry of Natural Products, held in Brussels, Belgium. Lewis Bases. The environmental factors used by Prof. Shemyakin and his colleagues are Lewis bases which interact with the phosphorus atom. The best Lewis bases, he says, are lithium iodide or bromide in dimethylformamide. "The reaction will still work in nonpolar solvents (such as benzene) but with highly dispersed lithium bromide or iodide," Prof. Shemyakin adds. One way in which a Lewis base could affect the course of the Wittig reaction would be to interact with the positive charge on the ylid phosphorus. The dipole-dipole line-up of the molecules would not then be possible, and the cis isomer would be favored.
Wittig reaction may follow this steric course The more sterically favored course leads to trans isomer
?h3P
Ph3p-
15
c —=5BP" c, C Cv
c
R
R'
0
?h 3 p
o
Ph,P
co
~^*" C, c
-C c
=— c C = -cR * < HM M R
'H H
R
'tf H
R
*
0
trans isomer
but cis isomer can also result. . .
?h 3 ? +
?h3P H C R
c
cR
O
'H
o
The Wittig reaction usually involves dipole-dipole interaction of a phosphorane and a carbonyl compound. Orientation of the product depends on how the two molecules approach. 36
C&EN
o
Ph,P^
o
R C
H
"Pha?-
JULY
2 3, 1 9 6 2
c.
c PL
H R:
: /0
R \
c
R/^H
cis isomer The sterically favored course of the reaction leads to a trans product Rotation around the carbon atoms to bring oxygen in line with the phosphorus could also give the cis isomer
W i t h Lewis bases of similar species, Prof. S h e m y a k i n finds t h a t t h e relative yield of cis isomer goes u p as nucleophilicity increases (for e x a m p l e , C l ~ < Br~ < I - , and methyl-p-aminob e n z o a t e < aniline < p h e n y l h v d r a z i n e < A 7 ? A 7 -dimethyl-p-phenylene diamine). At t h e same time, h e says, t h e amine's effect d e p e n d s on steric factors a n d yield falls sharply with increased substitution—for instance, e t h y l a m i n e > d i e t h y l a m i d e > triethylamine. "Lewis bases h a v e little influence on the steric course of t h e reaction w h e n an electron a c c e p t o r g r o u p is a t t a c h e d to t h e ylid carbon a t o m , " Prof. Shemyakin says. F o r e x a m p l e , t h e reaction
of c a r b e t h o x y m e t h y l e n e t r i p h e n y l p h o s p h o r a n e w i t h b e n z a l d e h y d e gives t h e trans-cinnamic ester, n o t w i t h s t a n d i n g t h e p r e s e n c e of Lewis bases. A r m e d with these results, Prof. Shemyakin a n d his co-workers are able to synthesize stereospecifically a series of u n s a t u r a t e d n a t u r a l p r o d u c t s with cis configuration of t h e e t h y l e n i c bond. T h e t e c h n i q u e is particularly suited to t h e p r e p a r a t i o n of u n s a t u r a t e d h i g h e r fatty acids. "But," Prof. Shemyakin adds, "while this is t r u e for all conditions using only a l d e h y d e s , it does not w o r k successfully w i t h ketones to t h e s a m e extent. W e are n o w working on t h e ketone problem."
i
S'S
FREE Reference —i Sheets on
Selectacel
ION EXCHANGE CELLULOSES for use in chromatographic columns New Selectacel Ion Exchange Celluloses have remarkable properties when used with ionic and colloidal materials of high molecular weight. Such applications include —
Structure leads to trans isomer
• ENZYMES • PROTEINS • HORMONES
C
Ph 3 ?
-h
c
There are several kinds of Seleciacel Ion Exchange Celluloses:
c —— c
ANION EXCHANGERS Type DEAE (Diethylaminoethyl Cellulose)
+
+ B:
c
Type CM (Carboxymethyl
affect t h e course of t h e W i t t i g reaction
Type P
t h e ylid p h o s p h o r u s ,
* '
\
\
a r a n d o m position in relation to it.
Capacity meq/g 0.3
Grade Standard 20 40
Capacity meq/g 0.7
|
carbon-carbon bond
MAIL COUPON TODAY
\
U s i n g this variation of
T>hj-p=0
Professor M . M . S h e m y a k i n
Grade Standard
Capacity meq/g
(Cellulose 0.9 Phosphate) Bifunctional — containing both strongly acidic and weakly acidic groups. Relatively high exchange capacities.
Orientation around the
t h e W i t t i g reaction,
Grade Standard 20 40
Weakly acidic —most effective at pH's slightly above 4.
is b y interaction w i t h
leads to a cis o r i e n t e d p r o d u c t .
0.9
CATION EXCHANGERS
?h,P^
Capacity meq/g
Separation and purification of viruses.
V
t h u s allowing oxygen to take u p
Type ECTEOLA (Epichlorohydrin triethanolamine)
/ \ R'A, A likely r o u t e w h e r e b y L e w i s b a s e s
Grade Standard 20 40
Separation and purification of proteins, peptides, enzymes, hormones and reiated materials.
\
p I
ACIDS
These materials produce separations that far exceed what usually can be accomplished alone by ion exchange resins, chromatography, electrochromatography, or electrophoresis.
