Transacylation Intramolecular

C-transacylation, intramolecular W agne r-Meerwein rearrangement Walden inversion... 

A recent total synthesis of tubulysin U and V makes use of a one-pot, three-component reaction to form 2-acyloxymethylthiazoles <06AG(E)7235>. Treatment of isonitrile 25, Boc-protected Z-homovaline aldehyde 26, and thioacetic acid with boron trifluoride etherate gives a 3 1 mixture of two diastereomers 30. The reaction pathway involves transacylation of the initial adduct 27 to give thioamide 28. This amide is in equilibrium with its mercaptoimine tautomer 29, which undergoes intramolecular Michael addition followed by elimination of dimethylamine to afford thiazole 30. The major diastereomer serves as an intermediate in the synthesis of tubulysin U and V. 

The reluctance of tertiary amides to undergo hydrolysis, especially those produced in the Birch reduction-alkylation with a quaternary center next to the carbonyl group, has inspired the development of a variety of intramolecular transacylation reactions as illustrated by the cleavage of the SEM ether in 16... 

Bobowsky and Shavel found an interesting intramolecular reductive transacylation reaction, in which substituted cyclopent[e][l,3]oxazin-2-ones and l,3-perhydrobenzoxazin-2-ones (90) were formed (80JHC277). In the reactions of 4-(2 -oxocycloalkyl)-3,4-dihydro-3-methyl-2//-l,3-benzoxazin-2-ones 88 and potassium borohydride, the 2 -hydroxycycloalkyl products 89 obtained underwent intramolecular transacylation reactions, resulting in the dihydro-1,3-oxazine derivatives 90. In this way, the 4-(2 -oxocycloalkyl)... 

Scheme 22 Intramolecular Transacylation of Thioesters To Form Dipeptides 106 ...

Scheme 23 Intramolecular Transacylation of Thioesters for the Synthesis of a Protein[107 1121 NH2...

The mechanism of the Passerini reaction was widely examined. A plausible mechanism that is consistent with experimental data is as follows First, the carbonyl compound and the carboxylic acid forms a hydrogen bonded adduct. Subsequently, the carbon atom of the isocyanide group attacks the electrophilic carbonyl carbon, and also reacts with the nucleophilic oxygen atom of the carboxylic acid. The resulting intermediate cannot be isolated as it rearranges to the more stable a-acyloxycarboxamide in an intramolecular transacylation. 

Acetylation of 2-methoxynaphthalene by acetic anhydride over HBEA zeolite gives l-acetyl-2-methoxynaphthalene, 2-acetyl-6-methoxynaphthalene and a small amount of l-acetyl-7-methoxynaphthalene (equation 45) . The l-acetyl-2-methoxynaphthalene rearranges to the other isomers under longer contact times, probably involving both intermolecular transacylation and intramolecular rearrangements (equation 46). 

Imidazole-based Ylides (Table 8, entry 36) Polymer-bound acyl imidazolinium species display special reactivity. They can be deprotonated at their C-atom to form azolium yhdes, which can be trapped with benzaldehyde. Intramolecular transacylation involving the polymer-bound carboxyl group ensues to give the a-acyloxy methyl imidazole [487] (Scheme 136). 

With dimethylacetylene dicarboxylate (DMAD) 1-acylimidazoles form novel functionalized derivatives as a consequence of electrophilic attack on the pyridine nitrogen followed by intramolecular transacylation (Scheme 112) <88CC1151,90JCS(P1)1821,92CB1939>. Ketoximes undergo Beckmann rearrangement and primary carboxamides are dehydrated to nitriles on treatment with (170)... 

Scheme 5.4 shows a one-step three-component synthesis of the medicinally important P-lactam 1 by simply mixing a P-amino acid, an aldehyde, and an isonitrile. In this example, the amine and carboxylic acid were tethered together in the form of a P-amino acid. The reaction proceeded according to the Ugi mechanism leading to a cyclic imidate intermediate, which upon intramolecular transacylation afforded the observed cyclic product [14]. 

Three different mechanisms have been proposed [1] for the Fries rearrangement with AICI3 (i) an intramolecular mechanism with a direct acyl shift from the oxygen atom to a carbon atom of the ring (ii) a monomolecular deacylation-acylation mechanism with an acyl chloride intermediate and (iii) an intermolecular mechanism (transacylation). 

The Fries rearrangement of phenyl acetate (PA) over solid-acid catalysts was first studied in a fixed bed reactor at 400 °C by Pouilloux et al. [9,10]. o- and p-Hydro-xyacetophenone (o- and p-HAP), p-acetoxyacetophenone (p-AXAP), and phenol (P) were the main reaction products. Fluorinated alumina and H-FAU zeolites afforded approximately the same product distribution, o-HAP being highly favored over the para isomer. The reaction scheme proposed was that PA dissociates into phenol (P) and ketene and that o-HAP results partly from an intramolecular rearrangement of PA and partly from transacylation (Eq. 2) whereas p-HAP results from the latter reaction only [10]. 

C.H. Johnson, T.J. Athersuch, I.D. Wilson, L. Iddon, X. Meng, A.V. Stachulski, et aL, Kinetic and J-resolved statistical total correlation NMR spectroscopy approaches to structural information recovery in complex reacting mixtures apphcation to acyl gju-curonide intramolecular transacylation reactions. Anal. Chem. 80 (2008) 4886. 

In animals and microorganisms, NAPE appeared to be synthesized by a Ca " -dependent transacylase activity whereby a fatty acid is transferred from the 5 -lor -2 0-acyl position of a phospholipid to the ethanolamine head group of PE (Schmid et al., 1990). Evidence indicated that transacylation could occur intermolecularly (with PE, PC or cardiolipin able to serve as the acyl donor), or intramolecularly. Most notably, free fatty acids or acyl moieties from fatty acylCoA were not incorporated into NAPE. To date, this transacylase activity has not been solubilized from any membrane source in an active form. 

The acyl nitrene generated from compound (I6) led to products (17) and (18) by insertion, and product (19) by a novel intramolecular transacylation (Scheme 4) various similar model systems... 

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