200 Lcvcl 2 - Case 30
nes 3 in Scheme 30.1, that products derived from the other possible regioisomers 7
are not observed in the reaction. 1
LUMO
HOMO
LUMO
HOMO
NHAc
NHBOC
059~.....----....
N -;;:N
0.72JL
11
1
N~N 0.280 OEt
0.538 1 '-..._...A'
0.59~.....----...
N -;;: N
0.72JL
11
1
N~N
0.280 OEt
0.5491 ..........___"
SCH3
SCH3
1a
1b
(ELUMo-EHOMO = 6.61 eV)
(ELUMo-EHOMO = 6.63 eV)
!
R 1 =Ac, BOC
not formed
Scheme 30.4
In Summary
1 ,2,4,5-Tetrazines 1 undergo regioselective inverse electron demand Diels-Alder
reactions with a variety of electron-rich dienophiles to yield 1,2-diazines in good
yield. The process takes place in three steps: (a) [4+2] cycloaddition, (b) elimination ofthe electron-donating group, (c) extrusion of N 2 by means of a retro-DielsAlder process.
Questions
Once we have understood the mechanism of the cycloaddition between tetrazines
1 and electron-rich alkenes, we would be able to interpret the following experimental results:
1 Thc rcgiosclcctivity is consistent with thc polarization of thc dicnc and thc ability of thc
methylthio group to stabilize a partial negative charge at C-3 and the N-acylamino group
to stabilize a partial positive charge at C-6.