Select a protective group to get the conditions needed to install/remove the group. Several reaction samples of protection and deprotection are shown for each groups.
Carbonyl compounds having an -hydrogen act as weak (protic) acids and react with a base to yield enolate anions.
Presence of neighbouring carbonyl group increases the acidity of a ketone over an alkane by a factor of 1040! The use of such enolate anions from carbonyl compounds is fundamental to organic synthesis and you will already have met them as intermediates in the Aldol reaction and Claisen condensation.When we have two carbonyl groups adjacent to a methylene group, the acidity of the -H is greatly increased. Because of the acidity of their methylene (CH2) hydrogens, malonic esters, ethylacetoacetate and -dicarbonyl compounds etc are often called active hydrogen compounds.1)They are readily made and cheap2)The anion can be generated quantitatively3)Self condensation does not occur with 1 mole of base – OH is deprotonated4)The site of deprotonation is unambiguous5)The enolate ions formed on deprotonation can be alkylated and acylated offering useful products.Example:Most important use is for preparation of ketones (from -keto esters RCOCH2CO2Et) and of acids from malonic esters (CH2(CO2R)2).Note:
So Retrosynthesis:Note: FGI’s can be carried out on intermediates/products.Note especially:Helps in the synthesis of 1,3 diols.e.g.Usually uses weak base/weak acid as catalyst, (R2NH/HOAc). Any combination of stabilising groups can be used (CN, CO2Et etc).Carbanions derived from active methylene compounds react with-unsaturated compounds by 1,4-(conjugate) addition known as Michael addition.
We have discussed the regioselective reactions of this active methylene carbon (C-2) in ethylacetoacetate. Can regiospecifically trap C-4 via the dianion.Carbonyl Addition and Carbonyl Substitution – Aldol and Claisen Reactions.Usually self-condensations, these reactions combine nucleophilic attack and -substitution as the first step.Note the Aldol condensation can also be performed with acid catalysis in which dehydration usually follows (enol form is involved – mechanism p 773). NB dehydration drives the reaction when the equilibrium is unfavourable.
Note: the only difference between the Aldol and Claisen reaction is the fate of the tetrahedral intermediate – Claisen expels alkoxide, Aldol alkoxide is protonated.These are not very useful generally as there are four potential products. However, they can be useful if one component has no -H.Mixed AldolMixed Claisen CondensationsOnly successful when one of the ester components has no -H e.g.
Synthetic protecting groups for amino acids - [e]
The Fourth Edition includes significant developments in protective group chemistry since 1998. In addition to incorporating new protective groups now available to the synthetic organic chemist, such as the uniquely removable 2-methoxybenzenesulfonyl group for the protection of amines, the book also covers new techniques for the formation and cleavage of existing protective groups, providing the most relevant and useful examples to illustrate each methodology. The content is organized around the functional group to be protected (ethers, acids, carbonyl groups, amines, amides, phenols, etc.), and ranges from the simplest to the most complex highly specialized protective groups.
Protecting Groups in Organic Synthesis: Postgraduate Chemistry ..
This motivates the need for a protecting group. We need a way to block the alcohol from reacting while we do something else, and then freeing it up again. The canonical protecting group is some sort of silyl ether. The simplest way to achieve this is with as trimethylsilyl (TMS; Me3Si):
Protecting Groups in Solid-Phase Organic Synthesis - …
Which functional groups you want to protect and which protecting groups you wish to use for the job depends entirely on your desired sequence. In natural product synthesis, it is very common to transform alcohols into silyl ethers — I would want to argue that this is the most common usage of the term. Alcohols have the disadvantages that they are nucleophilic, weakly acidic, can coordinate metal centres and can even act as bases. If you transform the alcohol into a silyl ether, it is no longer acidic, its ligand properties are substantially impeded and it can no longer attack nucleophilicly. Thus, it is possible to perform reactions, e.g. titanium(IV) catalysed aldol additions, which would not be possible with free alcohols.
Protecting Groups in Solid-Phase Organic Synthesis
Sometimes it is also desireable to introduce different protecting groups to similar sites or to selectively cleave only some protecting groups. For example, you may have two primary alcohols and want to turn only one of them into an aldehyde; by clever choice of your reaction sequence and protecting group strategy you will arrive at a point where only one protecting group is easily removed to give only one of the two free alcohols selectively.
Protective Groups In Organic Synthesis - ResearchGate
While silyl groups — among them the relatively bulky tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS) and tetraisopropylsilyl (TIPS) groups are exceedingly common, not all protecting groups need be that large. Methoxymethyl (MOM) is a rather small protecting group that enables the alcohol (then acetalic oxygen) to keep its ligand properties. Even smaller is the methyl group used to protect carboxyl functions or, arguably the smallest, the chlorine atom, used by Woodward in his synthesis of 6-demethyl-6-deoxytetracycline.