Brønsted Acid‐Catalyzed Intramolecular 7‐endo Hydroarylation Reaction of 1,5‐Diaryl‐1‐pentynes

Abstract

A Brønsted acid-catalyzed, transition metal-free intramolecular 7-endo hydroarylation reaction of 1,5-diaryl-1-pentynes has been developed. The use of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent was found to be critical for this process. Using the present methodology, we have accomplished the synthesis of KGP-18, an analogue of the anticancer natural product combretastatin A4.

Bro̷nsted Acid-Catalyzed [5+1] and [4+1] Annulation of Cyclic Anhydrides with o-Alkynylanilines to Construct Fused-N-Heterocycles

“…Unfortunately, it produced uncyclized byproduct 5a (20%, entry 7). To our delight, sulfur-containing Bro̷nsted acid (entries 8–11) p -TsOH maximizes the yield (82%, entry 9) with subsidizing generation of byproduct 5a (3%). However, PhSO 3 H and trifluoromethyl sulfonic acid enhanced the generation of byproduct (20–40%, entries 10 and 11), and the desired product was not detected (entry 11).…”

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

“…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 cation‐stabilizing properties of fluorous solvents such as HFIP, we herein report a direct cyanation of benzyl alcohols with TMSCN as a cyanide source.…”

“…[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.…”

Synthesis of Seven- and Eight-Membered Rings by a Brønsted Acid Catalyzed Cationic Carbocyclization of Biphenyl Embedded Enynes

“…Moreover, the biphenyl core of enynes 1 could be decorated with electrondonating and/or -withdrawing groups, providing ketones 2j−o in good yields. 16 To broaden the utility of the methodology, we investigated the possibility of trapping carbocation IIa (Scheme 2) with C-nucleophiles. 17 For this purpose, reaction of 1a with 1,2-dimethoxybenzene (1.5 equiv) was conducted under the optimal conditions determined for generating ketone 2a.…”