Self‐Acylation of 1‐Adamantylacetic Acid in Trifluoroacetic Anhydride Medium: A Route to 2,4‐Bis(1‐adamantyl)acetoacetic Acid and Its Derivatives

Abstract

The self‐acylation of 1‐adamantylacetic acid (1) in trifluoroacetic anhydride, catalyzed by triflic acid, proceeds through the formation of the mixed 2,4‐bis(1‐adamantyl)acetoacetic–trifluoroacetic anhydride 2, and it was used as an efficient approach to previously unknown 2,4‐bis(1‐adamantyl)acetoacetic acid (3), its esters 4–6 and amides 7–11, and the sterically hindered 1‐adamantyl(1‐adamantylacetyl)ketene (12). The latter is stable in solution and can be isolated as a neat solid. Addition of methanol or primary amines to 12 gave the corresponding derivatives of acid 3. Acid 3 was decarboxylated to 1,3‐bis(1‐adamantyl)acetone (22), whereas theheterocyclization of phenyl ester 6 with thiourea gave two isomeric adamantylated thiouracils 23 and 24. The structures of N‐benzylamide 7 and thiouracil 23 were confirmed by single‐crystal X‐ray analysis. The utilization of the self‐acylation method for the conversion of some other aliphatic acids is discussed and preliminarily tested.

Preparation of the HIV Attachment Inhibitor BMS-663068. Part 6. Friedel–Crafts Acylation/Hydrolysis and Amidation

“…A process for the acylation of an indole derivative using Et 2 AlCl has been demonstrated on 3 kg scale, but these conditions were also not applicable to 6-azaindole 1 (Table , entry 2), providing only an approximately 19% conversion to acylated product 5 . Other reported procedures that utilized a combination of Grignard reagent and ZnCl 2 , 1,5-diazabicyclo[4.3.0]­non-5-ene (DBN), various Lewis acids, or a strong Brønsted acid, also performed poorly with our substrate (Table , entries 3–8). It has been reported that numerous electron-rich indole substrates can be acylated in the absence of pretreatments or catalysts; however, our substrate was again completely inert when subjected to these conditions (Table , entry 9) …”

(CF3CO)2O/CF3SO3H-mediated synthesis of 1,3-diketones from carboxylic acids and aromatic ketones

“…By acylation of 1-indanone ( 2a ) with (diphenylphosphoryl)acetic acid ( 1j ), the self-acylation of the acid 1j already occurred at room temperature, which complicated the separation of the desired dicarbonyl compound. When the acid 1j was heated under the conditions of TFAA/TfOH-mediated self-acylation of alkanoic acids recently reported by us [ 27 ] and decarboxylation was subsequently carried out, 1,3-diphenylphosphorylated acetone 5 could be obtained (reaction 2 in Scheme 2 ).…”