Nucleophilic groups formation

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

Stretching then breaking of the bond to the leaving group Formation of a bond to the nucleophile from the opposite side of the bond that is broken... 

Step 1 of Figure 27.7 Claisen Condensation The first step in mevalonate biosynthesis is a Claisen condensation (Section 23.7) to yield acetoacetyl CoA, a reaction catalyzed by acetoacetyl-CoA acetyltransferase. An acetyl group is first bound to the enzyme by a nucleophilic acyl substitution reaction with a cysteine —SH group. Formation of an enolate ion from a second molecule of acetyl CoA, followed by Claisen condensation, then yields the product. 

The processes of complex-ion formation referred to above can be described by the general term complexation. A complexation reaction with a metal ion involves the replacement of one or more of the coordinated solvent molecules by other nucleophilic groups. The groups bound to the central ion are called ligands and in aqueous solution the reaction can be represented by the equation ... 

Cyclic structures can form as a result of side reactions. One of the most common examples is the formation of diketopiperazines during the coupling of the third amino acid onto the peptide chain (Fig. 7). Intramolecular amide bond formation gives rise to a cyclic dipeptide of a six-membered ring structure, causing losses to the sequence and regeneration of the hydroxyl sites on the resin. The nucleophilic group on the resin can lead to fiuther unwanted reactions [14]. 

Figure 4.21 BASED can react with molecules after photoactivation to form crosslinks with nucleophilic groups, primarily amines. Exposure of its phenyl azide groups to UV light causes nitrene formation and ring expansion to the dehydroazepine intermediate. This group is highly reactive with amines. The cross-bridge of BASED is cleavable using a disulfide reducing agent.

The presence of strongly nucleophilic groups in either the donor or the acceptor can be problematic in sulfoxide-type glycosylations when activation is conducted with triflic anhydride. The most common culprit is the amide group [340,341], which is illustrated by the formation of a dihydrooxazine when a 3-acetamido alcohol was employed as acceptor (Scheme 4.47) [342]. Self-evidently, acceptor-based problems of this type could be avoided by the preactivation of the sulfoxide with triflic anhydride. 

Allenic amino acids belong to the classical suicide substrates for the irreversible mechanism-based inhibition of enzymes [5], Among the different types of allenic substrates used for enzyme inhibition [128, 129], the deactivation of vitamin B6 (pyr-idoxal phosphate)-dependent decarboxylases by a-allenic a-amino acids plays an important role (Scheme 18.45). In analogy with the corresponding activity of other /3,y-unsaturated amino acids [102,130], it is assumed that the allenic amino acid 139 reacts with the decarboxylase 138 to furnish the imine 140, which is transformed into a Michael acceptor of type 141 by decarboxylation or deprotonation. Subsequent attack of a suitable nucleophilic group of the active site then leads to inhibition of the decarboxylase by irreversible formation of the adduct 142 [131,132]. 

Often, the basic group that is responsible for the proton abstraction is also the nucleophilic group in the Michael addition. Thus, most of the suicide inhibitors made so far have been aimed at enzymes that catalyze the formation of carban-ions or carbanion-like intermediates. Suicide inhibitors are typically based on acetylenic compounds (as in equation 9.8), /3, y-unsaturated compounds (as in equation 9.9), or /3-halo compounds (as in equation 9.10). (The a protons in such compounds are acidic because the negative charge in the carbanion is delocalized by the conjugation with X.)... 

Addition of primary amines to carbonyl groups follows the pattern we have established for other nucleophiles with formation of a carbinolamine (Equation 8.49). These compounds are sufficiendy stable to be isolated in some cases,87... 

In this connection it is noteworthy that not only a free hydroxyl group at C-3 but also a benzyloxy and methoxy group can act as internal nucleophiles in formation of the 3,6-anhydride bond.384 An alternative to this method is the substitution of the tosyloxy group at C-3 by the primary hydroxymethyl group at C-6 involving the intermediary formation of 2,3- or 3,4-oxirane ring (see Section V). 

---