Intramolecular transacylation reactions

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)... 

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. 

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. 

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]. 

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 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]. 

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