Page 304 - Advanced Organic Chemistry Part B - Reactions & Synthesis

276 derivatives can be prepared by exchange with other orthoesters, 270 by reaction with
iminoethers, 271 or by rearrangement of the ester derived from 3-hydroxymethyl-3-
CHAPTER 3 272
methyloxetane.
Functional Group
Interconversion (HOCH ) CCH
by Substitution, RC(OCH ) 2 3 3
Including Protection and 3 3
Deprotection
NH
(HOCH ) CCH 3 O
2 3
RCOR' R O CH 3
O
O
CH 3 BF 3
RCOCH 2
O

The latter method is improved by use of the 2,2-dimethyl derivative. 273 The
rearrangement is faster and the stability of the orthoester to hydrolysis is better. Isotopic
labeling showed that the rearrangement occurs by ionization at the tertiary position.
CH
CH 3 3
BF 3 *O CH 3
O CH 3 O Ph + CH 3 CH 3
O CH
COCH 2 O – O 3
Ph CH 3 O BF 3 Ph CH 3
O
Lactones can be protected as dithiolane derivatives using a method that is
analogous to ketone protection. The required reagent is readily prepared from trimethyl-
aluminum and ethanedithiol.

O
S S
O + (CH ) AlSCH CH SAl(CH )
2
3 2
2
3 2
O
Ref. 274
Acyclic esters react with this reagent to give ketene dithio acetals.
S
R CHCO R′ + (CH ) AlSCH CH SAl(CH ) R C
3 2
2
2
2
3 2
2
2
S
In general, the methods for protection and deprotection of carboxylic acids and
esters are not as convenient as for alcohols, aldehydes, and ketones. It is therefore
common to carry potential carboxylic acids through synthetic schemes in the form
of protected primary alcohols or aldehydes. The carboxylic acid can then be formed
at a late stage in the synthesis by an appropriate oxidation. This strategy allows one
to utilize the wider variety of alcohol and aldehyde protective groups indirectly for
carboxylic acid protection.
270 M. P. Atkins, B. T. Golding, D. A. Howe, and P. J. Sellers, J. Chem. Soc., Chem. Commun., 207 (1980).
271
E. J. Corey and K. Shimoji, J. Am. Chem. Soc., 105, 1662 (1983).
272
E. J. Corey and N. Raju, Tetrahedron Lett., 24, 5571 (1983).
273 J.-L. Griner, Org. Lett., 7, 499 (2005).
274
E. J. Corey and D. J. Beames, J. Am. Chem. Soc., 95, 5829 (1973).