Total Synthesis of Alanense A through an Intramolecular Friedel–Crafts Alkylation

Abstract

The first total synthesis of cadinane sesquiterpenoid alanense A, in which an intramolecular dehydrative Friedel− Crafts alkylation of 2,5-diaryl-2-pentanol is incorporated as a key step, has been achieved. The combinatorial use of p-TsOH•H 2 O as a catalyst and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent provides 1,1-disubstituted tetrahydronaphthalene in 97% yield. It was also found that the combination of p-TsOH and HFIP is effective for the removal of phenolic MOM ether.

Brønsted Acid Catalyzed Dehydroxylative Cyanation of Benzylic Alcohols with Trimethylsilyl Cyanide Using 1,1,1,3,3,3‐Hexafluoro‐2‐propanol as a Solvent

“…To demonstrate the synthetic potential of the protocol, we then evaluated the late-stage transformation of biologically active compounds (Scheme 5). First, it was found that treatment of podophyllotoxin (25) with TMSCN under the optimized Scheme 3. Substrate scope.…”

“…[22] Very recently, McCubbin and coworkers reported ferrocenium boronic acid 13-catalyzed dehydroxylative coupling of benzylic alcohols with carbon-and nitrogen-based borate and silane nucleophiles, in which α,α-diarylacetonitriles were obtained in moderate yields from α,α-diarylmethanols and TMSCN. [23] Recently, we have reported Brønsted acid-catalyzed intramolecular Friedel-Crafts reaction of 1,5-diaryl-1-alkynes 14 [24] as well as 2,5-diaryl-2-pentanol 16, [25] in which the use of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent, [26] which would effectively stabilize the cation intermediate, is critical for efficient cyclization (Scheme 2). In continuation of our studies on Brønsted acid-catalyzed transformation utilizing cationstabilizing properties of fluorous solvents such as HFIP, we herein report a direct cyanation of benzyl alcohols with TMSCN as a cyanide source.…”