Page 192 - Advanced Organic Chemistry Part B - Reactions & Synthesis

164 This methodology was also used in the connecting of two major fragments in the
synthesis of spongistatins. 252
CHAPTER 2
OTBDMS
Reactions of Carbon
Nucleophiles with OTBDMS H CH 3
Carbonyl Compounds CH O CH
+
3 P Ph I – CH 3 O H
CH O 3 O OCH O
3 3
H CH 3 H
O CH Li-LiBr O OCH 3
3
H CH 3 H TBDMSO O o O
+ THF - 78 C TBDMSO
O
H O O
OTES
H
OTES O
CH 3
CH 3
These conditions were also employed for a late stage of the synthesis of
(+)-discodermolide (see Entry 17, Scheme 2.17).
2.4.1.2. Olefination Reactions Involving Phosphonate Anions. An important
complement to the Wittig reaction involves the reaction of phosphonate carbanions
with carbonyl compounds. 253 The alkylphosphonic acid esters are made by the reaction
of an alkyl halide, preferably primary, with a phosphite ester. Phosphonate carbanions
are generated by treating alkylphosphonate esters with a base such as sodium hydride,
n-butyllithium, or sodium ethoxide. Alumina coated with KF or KOH has also found
use as the base. 254
O
RCH X + P(OC H ) RCH P(OC H ) + C H X
2 5
2 5 2
2
2
2 5 3
O O
base –
RCH P(OC H ) RCHP(OC H )
2
2 5 2
2 5 2
O O O
–
– O –
RCHP(OC H ) + R′ C O P(OC H ) R′ C CHR + (C H O) P O
2 5
2
2 5 2
2
2
2 5 2
R′ C CHR
2
Reactions with phosphonoacetate esters are used frequently to prepare -
unsaturated esters. This reaction is known as the Wadsworth-Emmons reaction and
usually leads to the E-isomer.
O
base R
CCH P(OC H )
R′O 2 2 2 5 2 + O CHR R′O 2 C
The conditions can be modified to favor the Z-isomer. Use of KHMDS with 18-
crown-6 favors the Z-product. 255 This method was used, for example, to control the
252
M. T. Crimmins, J. D. Katz, D. G. Washburn, S. P. Allwein, and L. F. McAtee, J. Am. Chem. Soc.,
124, 5661 (2002); see also C. H. Heathcock, M. McLaughlin, J. Medina, J. L. Hubbs, G. A. Wallace,
R. Scott, M. M. Claffey, C. J. Hayes, and G. R. Ott, J. Am. Chem. Soc., 125, 12844 (2003).
253 For reviews of reactions of phosphonate carbanions with carbonyl compounds, see J. Boutagy and
R. Thomas, Chem. Rev., 74, 87 (1974); W. S. Wadsworth, Jr., Org. React., 25, 73 (1977); H. Gross and
I. Keitels, Z. Chem., 22, 117 (1982).
254 F. Texier-Boullet, D. Villemin, M. Ricard, H. Moison, and A. Foucaud, Tetrahedron, 41, 1259 (1985);
M. Mikolajczyk and R. Zurawinski, J. Org. Chem., 63, 8894 (1998).
255
W. C. Still and C. Gennari, Tetrahedron Lett., 24, 4405 (1983).