Page 205 - Advanced Organic Chemistry Part B - Reactions & Synthesis

2.5. Reactions Proceeding by Addition-Cyclization 177

SECTION 2.5
The reactions in this section correspond to the general Pathway D discussed
Reactions Proceeding by
earlier (p. 64), in which the carbon nucleophile contains a potential leaving group.
Addition-Cyclization
This group can be the same or a different group from the anion-stabilizing group. One
group of reagents that reacts according to this pattern are the sulfonium ylides, which
react with carbonyl compounds to give epoxides.
R O –
R O
+
R S CH 2 – + O CR′ 2 R′ R R′
2
+
R S R′ R R′
2
There are related reactions in which the sulfur is at the sulfoxide or sulfilimine oxidation
level. Another example of the addition-cyclization route involves -haloesters, which
react to form epoxides by displacement of the halide ion.
H O C
C 2 H 5 O 2 C C 2 5 2 –
O C 2 H 5 O 2 C O
–
C R +O CR′ 2 R R′ R′
X X R′ R R′
2.5.1. Sulfur Ylides and Related Nucleophiles

Sulfur ylides have several applications as reagents in synthesis. 282 Dimethylsul-
fonium methylide and dimethylsulfoxonium methylide are particularly useful. 283 These
sulfur ylides are prepared by deprotonation of the corresponding sulfonium salts, both
of which are commercially available.
O

+ NaCH SCH 3 +
2
(CH ) SCH I – (CH ) S CH 2 –
3 2
3
3 2
DMSO
dimethylsulfonium methylide
O O
NaH
(CH ) SCH I – (CH ) S CH 2 –
3 2
3
3 2
+ DMSO +
dimethylsulfoxonium methylide
Whereas phosphonium ylides normally react with carbonyl compounds to give
alkenes, dimethylsulfonium methylide and dimethylsulfoxonium methylide yield
epoxides. Instead of a four-center elimination, the adducts from the sulfur ylides
undergo intramolecular displacement of the sulfur substituent by oxygen. In this
reaction, the sulfur substituent serves both to promote anion formation and as the
leaving group.
O – O
+ – +
) S
R C O + (CH 3 2 CH 2 R C CH 2 S(CH ) R C CH + (CH ) S
3 2
2
3 2
2
2
2
O O – O O
+ –
R C O + (CH 3 ) 2 S CH 2 R C CH 2 S(CH ) R C CH + (CH ) S O
3 2
2
2
2
2
3 2
+
282 B. M. Trost and L. S. Melvin, Jr., Sulfur Ylides, Academic Press, New York, 1975; E. Block, Reactions
of Organosulfur Compounds, Academic Press, New York, 1978.
283
E. J. Corey and M. Chaykovsky, J. Am. Chem. Soc., 87, 1353 (1965).