Generation of the 7-Azabicyclo[4.3.1]decane Ring System via (4 + 3) Cycloaddition of Oxidopyridinium Ions

Abstract

Oxidopyridinium ions bearing an ester group at the 5-position undergo (4 + 3) cycloaddition reaction to afford congeners of 7-azabicyclo[4.3.1]­decane. The reaction generally proceeds in high yield, although an excess of diene is often required to achieve such yields. The reaction is highly regioselective, but not endo/exo selective. It appears the cycloaddition process can be either kinetically or thermodynamically controlled, depending on the nature of the diene used and the reaction time. An intramolecular Heck reaction was used to demonstrate that some chemistry is possible with the cycloadducts.

Endo Selectivity in the (4 + 3) Cycloaddition of Oxidopyridinium Ions

“…This diene gave two cycloadduct isomers, 20a + b , in approximately equal amounts (46:54). As expected from our previous studies, the products had identical regiochemistry. Their relative stereochemistry was assigned on the basis of their NMR spectra .…”

“…We recently reported a highly regioselective (4 + 3) cycloaddition of N -methyloxidopyridinium ions with dienes (Scheme ). A related reaction of N -aryloxidopyridinium ions was introduced by Katritzky, while Cha studied its potential application in natural product synthesis. Although these studies suggested great promise for this type of process, one of the difficulties not yet overcome has been to achieve high levels of endo / exo diastereoselectivity.…”

“…As expected from our previous studies, the products had identical regiochemistry. Their relative stereochemistry was assigned on the basis of their NMR spectra . The lack of diastereoselectivity observed with 9h confirms that the silyl group was indeed responsible for the highly diastereoselective cycloadditions of 9a – g .…”

“…In these reactions, the silyl group leads to a slight erosion of the regioselectivity, producing small amounts (0–6%) of the minor endo regioisomers 13c – 19c . In our earlier work, other 2-substituted dienes like isoprene and 2-methoxybutadiene reacted well with 1 but gave low regioselectivity . Therefore, any regiochemical preference observed with 2-silyl dienes was of interest, even if it worked against the regiochemical preference of the terminal substituent on the diene.…”

“…Those of 13a , b are 93.7 and 91.4 ppm. These shifts lead to the stereochemical/regiochemical assignments shown, based on our previous work . Reaction of this cycloadduct with TBAF afforded a 75% yield of the desilylated cycloadducts 28a + b as an 89:11 mixture of isomers (Scheme ).…”