1,3-Dipolar cycloaddition of 5-methoxy-1-methyl-3-oxidopyridinium

3‐Oxidopyridinium Ions Are Versatile Bioorthogonal Dipoles for Use in Cycloadditions with Cyclooctynes

“…To investigate the kinetics of the cycloaddition reaction of DIBO with 5-substituted-3-oxidopyridiniums, the bimolecular rate constants, k 2 , were determined using UV-Vis absorption spectroscopy under pseudo-first-order kinetic conditions (Scheme 2, Table 1). Consistent with what has been previously published on 3-oxidopyridiniums, [12] the addition of an EDG meta to both the hydroxy anion and pyridinium nitrogen significantly increased the rate of the reaction, and the addition of electron withdrawing substituents resulted in a significant reduction in rate.…”

“…[10] These reactions were slow; however, subsequent work demonstrated that faster reactions with a wider scope of olefins can be achieved by placing an electron withdrawing group at the N1, making a better electron sink, [11] or by the addition of electron donating groups (EDGs) to the ring to activate C2. [12] In this work we sought to take advantage of the wide range of reactivity of 3-oxidopyriniums by introducing substituents on the 5 position of the pyridinium to favour the [3 + 2] dipolar cycloaddition with dipolarophiles commonly used in bioorthogonal reactions.…”

“…N ‐methyl‐3‐oxidopyridinium was the first 3‐oxidopyridinium studied and was found to react across the 2 and 6 positions as a 1,3‐dipole with electron deficient unsymmetrical olefins, with the O at position 3 anti to the substituent on the dipolarophile to form N ‐methyl‐8‐azabicyclo[3.2.1]‐3‐en‐2‐ones [10] . These reactions were slow; however, subsequent work demonstrated that faster reactions with a wider scope of olefins can be achieved by placing an electron withdrawing group at the N1, making a better electron sink, [11] or by the addition of electron donating groups (EDGs) to the ring to activate C2 [12] …”

Reaction of protoberberine-type alkaloids. Part 12. A facile method for regiospecific oxygenation and excited oxidative ring-cleavage of berberine alkaloids

“…153-155" (lit.,2s 248-150"), 6 ([,HJbenzene) 2. 25 (2 H , t, J 7 Hz, ArCH,CH,N<), 2.59 ( 1 H , dd, J 1 7, J, 14 Hz, ArCH,CHHN<), 2.86 ( 1 H, dd, J 1 7, J 2 14 Hz, ArCH,CHHN<), 3.35 and 3.61 (each 3 H , s, ArOMe), 5.37 (2 H, s, -OCH,O-), 6.13 (1 H, s, -COO-CH-N<), 6.50 and 7.43 (each 1 H, d, J 8 Hz, ArH), and 7.73 and 7.82 (each 1 H, s, ArH), v, , , , .…”