Aldehydes oxygen-containing nucleophile

The reaction is based upon the two components condensation between an aldehyde or ketone 6 (or their synthetic equivalents) and alcohol 95, which contains an allylsilane (or vinylsilane) moiety. The IMSC reaction is mediated by Lewis or Bronsted acids, which activate the carbonyl group of 6 towards nucleophilic attack. After addition of alcohol 95 on the activated carbonyl, the oxonium cation 96 is formed, which is intramolecularly captured by the pendant allylsilane function, leading to oxygen-containing rings 97 (Scheme 13.38). This process typically requires a stoichiometric (or more) amount of Lewis acid. 

Aldehydes that contain a heteroatom substituent at the a-carbon often display high stereoselectivity in reactions with ally lie stannanes. This behavior is particularly the case for heteroatom substituents permitting effective chelation with a Lewis acid. Internal activation of the carbonyl oxygen provides a five-membered chelation complex with Lewis acids, which minimally offer two coordination sites. The stability of the metallocycle may account for high diastereoselection, as nucleophilic approach of the stannane occurs to the less hindered face of the carbonyl. 

You see in Chapter 10 that aldehydes and ketones contain a carbonyl group attached to carbon or hydrogen atoms. In the case of carboxylic acids and their derivatives, a carbonyl group is attached to an electronegative element such as oxygen, chlorine, or nitrogen. The presence of these elements tends to increase the 5+ charge on the carbonyl carbon, which makes the carbon atom more susceptible to nucleophilic attack. 

Addition reactions occur in compounds having n electrons in carbon-carbon double (alkenes) or triple bonds (alkynes) or carbon-oxygen double bonds (aldehydes and ketones). Addition reactions are of two types electrophilic addition to alkenes and alkynes, and nucleophilic addition to aldehydes and ketones. In an addition reaction, the product contains all of the elements of the two reacting species. 

In these reactions, the C2-atom of ThDP must be deprotonated to allo v this atom to attack the carbonyl carbon of the different substrates. In all ThDP-dependent enzymes this nucleophilic attack of the deprotonated C2-atom of the coenzyme on the substrates results in the formation of a covalent adduct at the C2-atom of the thiazolium ring of the cofactor (Ila and Ilb in Scheme 16.1). This reaction requires protonation of the carbonyl oxygen of the substrate and sterical orientation of the substituents. In the next step during catalysis either CO2, as in the case of decarboxylating enzymes, or an aldo sugar, as in the case of transketo-lase, is eliminated, accompanied by the formation of an a-carbanion/enamine intermediate (Ilia and Illb in Scheme 16.1). Dependent on the enzyme this intermediate reacts either by elimination of an aldehyde, such as in pyruvate decarboxylase, or with a second substrate, such as in transketolase and acetohydroxyacid synthase. In these reaction steps proton transfer reactions are involved. Furthermore, the a-carbanion/enamine intermediate (Ilia in Scheme 16.1) can be oxidized in enzymes containing a second cofactor, such as in the a-ketoacid dehydrogenases and pyruvate oxidases. In principal, this oxidation reaction corresponds to a hydride transfer reaction. 

The carbonyl group, C=0, provides a site for nucleophilic addition. The funtional group contains mobile tt electrons that pull strongly toward oxygen, this makes the carbonyl carbon electron-deficient and the carbonyl oxygen electron-rich. The molecule is flat due to the sp hybridization of the carbon. Consequently, it is open to relatively unhindered attack from above or below. Since the carbonyl carbon is electron-deficient, it is susceptible to attack by electron-rich, nucleophilic reagents such as bases. This typical reaction of aldehydes and ketones may be written as ... 

For all of these kinds of carbonyl-containing compounds (aldehydes, ketones, carboxylic acids, etc.), some properties of which are provided for some of the more simple members in Table 9.2, it might be anticipated that protonation of the non-bonded electrons (Chapter 1) on oxygen would increase the electron deficiency at the carbon of the carbonyl and facilitate attack at that carbon by nucleophiles. It might further be expected that, since the carbon of the carbonyl is positive, protons on the carbon adjacent to the carbon of the carbonyl (i.e., the a-carbon) would be particularly acidic (relative to protons on carbon not in such a position). In addition, it might be anticipated that the positive carbon of the carbonyl would exert an influence on sites of unsaturation (both double and triple bonds) that were conjugated with the carbonyl (i.e., a,P-unsaturated). 

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