Page 32 - Tyrosine-Based Bioconjugations - Jorick Bruins
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Chapter 1
1.4. Strain-Promoted Oxidation-Controlled ortho-Quinone cycloaddition (SPOCQ)
We recently showed that quinones undergo fast strain-promoted oxidation-controlled ortho- quinone cycloaddition (SPOCQ) with bicyclo[6.1.0]nonynes (BCN).128, 129 In a model reaction between 4-tert-butyl-1,2-quinone (Figure 7A, 44) and BCN-alcohol (45), a reaction rate of 496 ± 70 M-1 s-1 was determined, leading to the cycloaddition product (46). A noteworthy observation is that SPOCQ proceeds via an inverse-electron demand Diels–Alder cycloaddition of the LUMO of the quinone with the HOMO of BCN. As a logical consequence, the strained alkyne DIBAC,66 also known as DBCO, reacts over 1000x slower (0.19 M-1 s-1) than BCN, due to its much lower- lying HOMO orbital. This difference in reactivity between strained alkyne and quinone parallels that of the relative reaction rate with 1,2,4,5-tetrazine or electron-poor azide.68, 130, 131
Figure 7. SPOCQ between (A) tert-butyl quinone and BCN-OH, (B) genetically encoded BCN-lysine and quinone-bearing probe, and (C) oxidation of L-DOPA into a quinone and subsequent SPOCQ with BCN- bearing probe.
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