Aldol synthesis mechanism, mechanism of the aldol addition
The self-aldolization of aldehydes can usually be stopped at the aldol stage, with more vigorous conditions or a separate dehydration step needed to form the enal. This requires appropriate diastereocontrol in the Mukaiyama aldol addition and the product silyloxycarbenium ion to preferentially cyclize, rather than undergo further aldol reaction.
There are many examples of this type of stereocontrol: In reality, only some metals such as lithium and boron reliably follow the Zimmerman—Traxler model. Crossed-aldol reactant control[ edit ] The problem of "control" in the aldol addition is best demonstrated by an example.
A typical substrate for this situation is when the deprotonatable position is activated by more than one carbonyl-like group. Many methods which control both relative stereochemistry i.
A more sophisticated Robinson mechanism is shown below. Combined with isotopic labelling evidence and computational studiesthe proposed reaction mechanism for proline-catalyzed aldol reactions is as follows: In the present experiment, sufficient ethanol is present as solvent to readily dissolve the synthesis material, benzaldehyde and also the intermediate, benzalacetone.
Ester, amide and carboxylate enolates also react well with ketones to form aldol products, but intermolecular ketone-ketone crossed aldols are generally unsuccessful with alkali metal enolates, as are most aldol reactions involving aldehyde enolate donors. In contrast, retro-aldol condensations are rare, but possible.
A superior method, in principle, would avoid the requirement for a multistep sequence in favor of a "direct" reaction that could be done in a single process step. DOI Robinson annulations can also be initiated by the reaction of preformed enolates with Michael acceptors.