Solid-phase synthesis supports are like solvents

✍ Scribed by Anthony W. Czarnik

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 78 KB
• Volume: 61
• Category: Article
• ISSN: 0006-3592
• DOI: 10.1002/(sici)1097-0290(199824)61:1<77::aid-bit13>3.0.co;2-6

✦ Synopsis

What's wrong with this picture? That's right . . . it's missing the solvent. Is this a trivial omission? Not if it's your job to reproduce this reaction in your own lab.

Now, what's wrong with this picture?

That's . . . . . . . . right. It's missing the information about which solid-phase synthesis support was used. Is this a minor omission? Again, the answer is no.

Solid-phase synthesis supports are like solvents. That is, the environment in which two reactants collide has a profound influence on how fast they will react. This is so clearly true in the case of solvents that I need not spend any time providing examples. But if my feedback from the solid-phase organic synthesis (SPOS) community is a guide, there's a vital lesson yet to be internalized: In any SPOS reaction scheme, that little ''ball'' a reactant is shown attached to is not generic. The nature of this ''ball'' can enormously affect the rate at which reactions will occur, just as does the choice of solvent.

Perhaps most importantly, your intuition in this regard is not as good as you think. Just a little evidence will make this case indelibly. Which resin affords the faster reaction rates: polystyrene or TentaGel? The answer: it depends on the reaction. Quantitative data to this effect already exists in the literature. In response to a call for examples, Dr. Yan provided the following unpublished comparisons, all run in DMF at room temperature:

1. Similar rates on TentaGel and polystyrene: 2.