The Demjanov and Tiffeneau-Demjanov one-carbon ring enlargements of 2-aminomethyl-7-oxabicyclo[2.2.1]heptane derivatives. The stereo- and regioselective additions of 8-oxabicyclo[3.2.1]oct-6-en-2-one to soft electrophiles.

Abstract

Nitrosation of 7-oxabicyclo[2.2.1]hept-5-en-2-exo- ylmethyl amine ( 20) gave 7-oxabicyclo[2.2.1]hept-5-en-2-exo- methanol ( 22) whereas 7-oxabicyclo[2.2.1]hept-5-en-2-endo- ylmethylamine ( 21) afforded a 1:1 mixture of 7-oxabicyclo[3.2.1]oct-6-en-2-ols ( 23) and 8-oxabicyclo[3.2.1]oct-3-en-2-ols ( 24). Nitrosations of 2-exo- ( 28) and 2 -endo- aminomethyl-7-oxabicyclo[2.2.1]hept-5-en-2-ol ( 29) gave mixtures of 8-oxabicyclo[3.2.1]oct-6-en-2-one ( 25) and 8-oxabicyclo[3.2.1]oct-6-en-3-one ( 37). The preference for the C(3) methylene group migration giving 25 was the best (12:1) in the case of the 2 -endo- aminomethyl alcohol 29. Compared with the nitrosations of bicyclo[2.2.1]heptane analogues, the 7-oxa bridge in 28 and 29 enhances the preference for the C(3) methylene group migration vs. the C(1) methine group migration. The Tiffeneau-Demjanov one-carbon ring enlargement reactions of 2-exo- aminomethyl-7-oxabicyclo[2.2.1]hepta-2-endo- ol ( 30). 2-exo- aminomethyl-5-chloro ( 32) and 2-exo- aminomethyl-6-chloro-7-oxabicyclo[2.2.1]hept-5-en-endo- ol ( 33) are also reported. Under kinetically controlled conditions, 8-oxabicyclo[3.2.1]oct-6-en-2-one ( 25) adds to electrophiles EX=PhSeCl, PhSeBr. 2,4-(NO) 2C 6H 3SCl with high stereo- and regioselectivity giving the corresponding 8-oxabicyclo[3.2.1]-octan-2-ones where E substitutes the exo position of C(6) and X the exo position of C(7).