Acyl transfer reactions substitution

This type of map can be used to discuss the different types of nucleophilic displacement reaction. Using the simplified version shown in Fig. 2 we have already seen that SN1 reactions, for instance the solvolysis of triarylmethyl halides, go through the separated ions in the top right-hand corner (Swain et al., 1953 Ritchie, 1971). At the opposite extreme, nucleophilic substitution at centres where the number of ligands can be increased may proceed over the bottom left-hand corner of the diagram. Examples are acyl transfer reactions and substitution at tetrahedral phosphorus centres (Alder et al., 1971) as well as substitution at square planar transition metal compounds (Wilkins, 1974). The nucleophilic reactions studied by Ritchie (1976), for which the rate... 

Nucleophilic acyl substitutions are also called acyl transfer reactions because they transfer the acyl group from the leaving group to the attacking nucleophile. The following is a generalized addition-elimination mechanism for nucleophilic acyl substitution under basic conditions. 

Nucleophilic acyl substitution is a common reaction in biological systems. These acylation reactions are called acyl transfer reactions because they result in the transfer of an acyl group from one atom to another (from Z to Nu in this case). 

This reaction is called a nucleophilic acyl substitution reaction because a nucleophile (Z ) has replaced the substituent (Y ) that was attached to the acyl group in the reactant. It is also called an acyl transfer reaction because an acyl group has been transferred from one group (Y ) to another (Z ). 

Thioesters and oxoesters are similar in their rates of nucleophilic acyl substitution, except with amine nucleophiles for which thioesters are much more reactive. Many biological reactions involve nucleophilic acyl substitutions referred to as acyl transfer reactions. The thioester acetyl coenzyme A is an acetyl group donor to alcohols, amines, and assorted other biological nucleophiles. 

Many reactions like this occur in living organisms, and biochemists call them acyl transfer reactions. Acetyl-coenzyme A, discussed in Special Topic E in WileyPLUS, often serves as a biochemical acyl transfer agent. Acyl substitution reactions are of tremendous importance in industry as well, as described in the chapter opening essay and Special Topic C in WileyPLUS. 

Acyl derivatives react with nucleophiles in an addition reaction to generate an unstable tetrahedral intermediate. The intermediate decomposes by an elimination reaction in which a group leaves to form a different acyl derivative. The overall process is called nucleophilic acyl substitution. The process is also called an acyl transfer reaction because it transfers an acyl group firom one group (the leaving group) to another (the nucleophile). 

Thioesters undergo the same kinds of reactions as esters and by similar mechanisms Nucleophilic acyl substitution of a thioester gives a thiol along with the product of acyl transfer For example... 

Acylium ion (Section 12 7) The cation R—C=0 Acyl transfer (Section 20 3) A nucleophilic acyl substitution A reaction in which one type of carboxylic acid derivative IS converted to another... 

Steps 1-2 of Figure 29.5 Acyl Transfers The starting material for fatty-acid synthesis is the thioesteT acetyl CoA, the ultimate product of carbohydrate breakdown, as we ll see in Section 29.6. The synthetic pathway begins with several priming reactions, which transport acetyl CoA and convert it into more reactive species. The first priming reaction is a nucleophilic acyl substitution reaction that converts acetyl CoA into acetyl ACP (acyl carrier protein). The reaction is catalyzed by ACP transacyla.se. 

Like all anhydrides (Section 21.5), the mixed carboxylic-phosphoric anhydride is a reactive substrate in nucleophilic acyl (or phosphoryl) substitution reactions. Reaction of 1,3-bisphosphoglycerate with ADR occurs in step 7 by substitution on phosphorus, resulting in transfer of a phosphate group to ADP and giving ATP plus 3-phosphoglycerate. The process is catalyzed by phospho-gjvcerate kinase and requires Mg2+ as cofactor. Together, steps 6 and 7 accomplish the oxidation of an aldehyde to a carboxylic acid. 

Step 5 of Figure 29.11 Acyl Transfer Acetyl dihydrolipoamide. a thioester, undergoes a nucleophilic acyl substitution reaction with coen/.yrne A to yield acetyl CoA plus dihydrolipoamide. The dihydrolipoamide is then oxidized back... 

FIGURE 7.34 Decomposition of the symmetrical anhydride of A-methoxycarbonyl-valine (R1 = CH3) in basic media.2 (A) The anhydride is in equilibrium with the acid anion and the 2-alkoxy-5(4//)-oxazolone. (B) The anhydride undergoes intramolecular acyl transfer to the urethane nitrogen, producing thelV.AT-fcwmethoxycarbonyldipeptide. (A) and (B) are initiated by proton abstraction. Double insertion of glycine can be explained by aminolysis of the AA -diprotected peptide that is activated by conversion to anhydride Moc-Gly-(Moc)Gly-0-Gly-Moc by reaction with the oxazolone. (C) The A,A -diacylated peptide eventually cyclizes to the IV.AT-disubstituted hydantoin as it ejects methoxy anion or (D) releases methoxycarbonyl from the peptide bond leading to formation of the -substituted dipeptide ester. 

In 1982 Cardillo used a three-step sequence involving two supported reagent systems to convert /i-iodoamines into amino alcohols (Scheme 2.23) [45]. Polymer-supported acetate ions were used for the substitution of the iodide which immediately underwent acyl transfer to the amine. The resulting compound (10) was directly treated with hydrochloric acid to cleave the amide and the free base was subsequently obtained from the reaction by treatment with a resin-bound carbonate. This was of particularly synthetic value because of the high water solubiHty of these amino alcohol compounds that would have made aqueous work-up challenging. 

A proposed mechanism for this transformation, provided in Scheme 42, is based on the identification of alcohol-carbene complexes by Movassaghi and Schmidt. Mesityl substituted imidazolinylidine carbene acts as a Brpnsted base as transesterification occurs to produce LXVII. Upon O N acyl transfer, the observed product is formed. The evidence provided for this mechanism includes the control experiment in which LXVII is resubjected to the reaction conditions and proceeds with amide formation. A similar mechanism has recently been reported in a theoretical study of transesterification by Hu and co-workers [139], In light of this work, it seems reasonable to suggest a similar that mechanism is operative in the transesterification reactions discussed throughout this section. 

As shown in previous sections, NHCs promote acyl transfer in transesterification reactions. In a similar manner, O C acyl transfer can be achieved with substrates such as 351 in the presence of 0.9 mol% of triazolium pre-catalyst 353 and KHMDS (Scheme 53). Moderate yields are obtained by varying substitution of the oxazole from R = Me, Ph, t-Bu, and t-Pr [171], Deprotonation of the triazolium salt followed by nucleophilic addition to the carbonate moiety of the oxazole results in enolate intermediate LXXXIII and activated carboxylate LXXXIV. Enolate addition and regeneration of the active catalyst provides quaternary stereocenters 352. 

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