Robinson annelation synthesis

Robinson annulation is a fundamental organic reaction in particular because it is at the base of the synthesis of steroids and other important molecules even of pharmaceutical interest. The reaction involves two important steps; 1) Michael addition 2) intramolecular aldol condensation .

The annulation reaction has as its most common substrates generally cycle hexanone and methyl vinyl ketone.

The first step involves the formation of cyclohexanone enolate and its nucleophilic Michael addition  to the methyl-vinyl-ketone (Michael acceptor).

Robinson Annelation

At this point, it quickly places an intramolecular aldol condensation. There are various possibilities of closing the cycle. The thermodynamically favored linear 6-terms cycle, in spite 4-terms cycles or bridged cycles.

The result of condensation is a  β-hydroxy ketone , which in the presence of a base, rapidly undergoes elimination (E1cb); elimination favored by the formation of a π-conjugated system (αβ - unsaturated).

Robinson Annelation part two

Therefore the overall reaction is (are highlighted new bonds formed):

Robinson Annelation overall reaction

If all the reactions that allow the formation of new C-C bonds are particularly studied and appreciated, the reaction of Robinson deserves a prominent place because according to a relatively simple method allows to obtain at the same time 2  C-C bonds. With a little imagination you can think that the methyl vinyl ether stretch two small arms (C-C bonds) to engage the hexanone cycle. The result is two 6-terms condensed cycles. In nature the molecules that have condensed cycles are very common.

Some examples of Robinson annulation

Examples of Robinson annulation

 

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