Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

1 .If 1 .m
The 2,6,7-trioxabicyclo[2.2.2]0ctane protecting group has been used to mask the
carboxyl group in several syntheses," most recentiy in the synthesis of laurencin?' a
member of the polyether toxins. Wipf et al. have recently introduced the 2,7.8-
trioxabicyclo[3.2. lloctane (AB0 esters) 1.72 as a structurally similar alternative to the
OB0 esters whose functionality may be incorporated as a desired backbone once
deprotection occurs.*
General use of 2,6,7-trioxabicyclo[2.2.2]octane began after 1982 when Corey and
Raju reported the facile preparation of 4-methyl-2,6,7-trioxabicycl0[2.2.2]octane ortho
ester (OB0 ester, 1.71) from the boron trifluoride etherate cataiyzed remangement of the
corresponding 3-methyl-3-hydroxymethyloxetane ester 1.73.1m Prior to this. ortho esters
had been obtained by the acid catalyzed esterification of the carboxylic acid with 2-
substihited-2-hydroxymethyl-1,3-propanediols.101 Most (acyclic) ortho esters are too
thermodynamically unstable relative to their hydrolysis products to allow this method to
be used? This increased stability makes the bicyclic ortho esters chromatographically
stable compared to their acyclic counterparts.lm Corey's procedure relies on the Lewis
acid catalyzed opening of the oxetane ester by carbonyl participation to form the 6-
rnembered zwittenon 1.75 (Scheme 1.3 1). Rearrangement generates the ortho ester 1.71.
with the ring angle strain of the oxetane providing the overdl thermodynarnic dnving
force. '00