Get ready for a tips-that-saved-my-life type of post for this one. Not with the idea to disappoint you, but this post will not help you to lose weight, improve your relationship with your boss or save your marriage. Rather than all that I have selected a “Top 5” of very simple organic chemistry reactions that at some point were crucial to the progress of my research projects.
Mitsunobu Reaction. Discovered by Oyo Mitsunobu. This reaction can be a very useful and straightforward alternative to nucleophilic substitutions and as in the case of SN2 it proceeds with inversion of configuration.
The Mitsunobu reaction allows the direct reaction of primary and secondary alcohols with acidic nucleophiles to afford products such as esters, ethers and amines among others. One of the reagents employed in the reaction, DEAD, (diethylazodicarboxylate) can be substituted by its cousin DIAD (diisopropylazodicarboxylate) if you are superstitious.
Sonogashira Coupling. In my opinion every single synthetic chemist must have cross-coupling reactions in their “synthesis toolbox”. Palladium catalysed cross-coupling reactions are unarguably of most relevance as reflected by the 2010 awarded chemistry nobel prize.
Discovered by Kenkichi Sonogashira, Sonogashira reaction allows the coupling of terminal alkynes with aryl or vinyl halides with a palladium catalyst, a copper(I) cocatalyst, and an amine as base.
Wittig reaction. Discovered by Georg Wittig, for which he was awarded the nobel prize in chemistry in 1979. The Wittig Reaction is probably the preferred method for synthetic chemists for making alkenes. The reaction allows the preparation of alkenes by the reaction of an aldehyde or ketone with the ylide generated from a phosphonium salt.
Triphenylphosphine oxide is generated in the process as a byproduct and sometimes it can be difficult to separate from the desired products. If you are sick of seeing that annoying triphenylphosphine oxide in your Wittig reactions you might want to take a look to the alternative proposed by O’Brien and co-workers from the University of Texas.
Selenoxide elimination. Another useful method for the synthesis of alkenes. Selenoxides decompose to the corresponding alkenes at mild temperatures and can be readily prepared from nucleophilic carbonyl derivatives by reaction with selenylating reagents such as PhSeCl in the presence of a base.
It is for this reason that selenoxide elimination has grown into a general method for the preparation of α,β-unsaturated carbonyl compounds.
Electrophilic aromatic halogenation. Electrophilic aromatic substitution is a general type of reactions you find in the first chapters of all organic chemistry books and you learn during the first semester of organic chemistry. Rule of thumb, electron-donor groups promote substitution at the ortho and para positions while electron-withdrawing groups promote the meta position.
In particular electrophilic halogenation is a very useful method to introduce diversity in the molecules as the aromatic halides generated can be easily modified for example with the use of cross-coupling reactions. Electrophilic aromatic halogenation can be performed in the presence of strong halogenating reagents in some cases although the use of Lewis acids is typically required.