Conjugate substitution

Dissolve the carrier protein in 0.1M MES, 0.15 M NaCl, pH 4.7, at a concentration of lOmg/ml. If using native, multi-subunit KLH, increase the NaCl concentration of all buffers to 0.9 M (yes, 0.9 M, not 0.9 percent) to maintain solubility of the protein. If using KLH subunits, the high-salt concentration is not necessary. For neutral pH conjugations, substitute 0.1 M sodium phosphate, 0.15M NaCl, pH 7.2, for the MES buffer. 

Lambert has exploited y-attack by an electrophile to bring about conjugate substitution at a tin center that is too highly sterically hindered to allow attack at the tin center itself (see Section 3.14.04.2).145... 

The other necessary reaction for a BN to VN isomerization is a well precedented 1,5 H shift to convert the linearly conjugated substituted cyclopentadiene (LCC) into the cross conjugated cyclopenta-diene (CCC). The relative lability of BN relative to VN is thus a reflection of the stabilizing conjugation of the substituent in the vinyl isomers and the fact that the formation of LCC from BN is more favorable than the formation of CCC from the retro Diels Alder of VN. The relative energetics for all of these processes is represented in a combined reaction profile diagram shown in Figure 1. 

Scheme 7.13 Lewis acid-catalyzed conjugate substitution of allylic alcohols.

Complementary to the conjugate substitution reaction in which the nucleophile is transferred directly from the tetraalkyl ferrate to the allylic ligand, preformed low-valent Fe complexes can form reactive allyl-iron complexes via an SN2 -type mechanism (path C, Equations (7.8) and (7.9), Scheme 7.16], These complexes react with incoming nucleophiles and electrophiles in a substitution reaction. Depending on the nature ofthe iron complex employed in the reaction, either o- or Jt-allyl complexes are generated. 

Palladium catalysed conjugate substitution via alkyl-alkenyl coupling preparation of 4-[( )-4-methyl-3-nonenyl]-2(5H)-furanone35a... 

Halogens are excellent leaving groups and are often used in conjugate substitution reactions. In the next example, two consecutive conjugate substitution reactions give a diamine. 

Each of the reactions is a conjugate substitution. It will be clearer if we draw the reaction with a generalized primary amine RNH2 first. 

In general, conjugate substitution is not nearly as important as the next topic in this chapter— nucleophilic aromatic substitution. Before we describe in detail those reactions that do occur, we need to explain why the most obvious reactions do not occur. 

The most important mechanism for aromatic nucleophilic substitution follows directly from conjugate substitution and we shall introduce it that way. It is called the addition-elimination mechanism . 

Imagine a cyclic p-fluoro-enone reacting with a secondary amine in a conjugate substitution reaction. The normal addition to form the enolate followed by return of the negative charge to expel the fluoride ion gives the product. 

Now imagine just the same reaction with two extra double bonds in the ring. These play no part in our mechanism they just make what was an aliphatic ring into an aromatic one. Conjugate substitution has become nucleophilic aromatic substitution. 

Draw detailed mechanisms for the last two steps in the ranitidine synthesis that involve conjugate substitution. Why is it possible to replace one MeS group at a time ... 

The Z factor for the conjugated substitutent is used when either the substituted or the double bond is further conjugated with other groups. 

Conjugate substitution electrophilic alkenes bearing leaving groups can promote substitution reactions at C=C related to those at C=0 Nucleophilic aromatic substitution electron-poor aromatic rings that allow substitution reactions with nucleophiles rather than the usual electrophiles... 

Just as direct addition to C=0 (Chapter 6) becomes substitution at C=0 (Chapter 12) when there is a leaving group at the carbonyl carbon, so conjugate addition becomes conjugate substitution if there is a leaving group, such as Cl, at the P carbon atom. Here is an example substitution has replaced Cl with OMe, just as it would have done in a reaction with an acyl chloride. 

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