Previous - 1.1 General approach (PLANNING)


1.2 Which Reaction? (PDF version)


1.         Write out possibilities (from memory)
2.         Carry out Scifinder search
3.         Refine : find 3-5 options which repeat regulary (i.e have most hits).
4.         Filter options above according to the following criteria:

- COST
Price of scale-up – too expensive for high throughput of material?
Note: depends where in sequence reagent occurs: end vs start

- TOXICITY
Avoid heavy metals: common villains: Cr/Hg/Sn/Pb/Se/
Toxic organic products               HMPA

- EASE OF CARRYING OUT
Things to watch out for
Special reagents required? commercially available? Requires synthesis?
Requires buying in reagent. (vs reagents in stock)
Anhydrous conditions required (vs wet/non anhydrous conditions)
Special handling conditions e.g glovebox.
High boiling point solvent required? DMF/DMSO/DMPU etc
Special apparatus? High pressure vessel/gas cylinder etc

- FUTURISTIC “COOL FACTOR”
Some reactions look better in publications e.g  those with Pd/Ru/organocatalysis/obscure reagents than classic tried and tested reagents.
Cross metathesis vs wittig reaction

- FUNCTIONAL GROUP COMPATIBILITY
Ensure the reactions conditions chosen are compatible with ALL the functional groups present in your molecule:
e.g Jones reagent (contains H2SO4) would not be compatible with acid sensitive groups such as acetals for example.

- INTUITION
Sometimes choice depends on intution as to what seems the best option – subtle combinations of the above factors which is difficult to express in words.

  1. Begin with easiest to carry out reaction.
  2. Refine approach based on what you find out by carrying out the reaction and the information you collected above.

 

Next - 1.3 Which Scale?