The Dual Role of 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) in the Synthesis of Terminal Aryl- and Styryl-Acetylenes via Umpolung Reactivity

Abstract

The dual role of the bicyclic amidine base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was demonstrated in a synthesis of terminal aryl- and styryl-acetylenes. Mechanistically, a tandem process involving elimination/Umpolung/protonation occurs in a single step to generate terminal aryl- and styryl-acetylenes from geminal dibromoalkenes. The key to the success of this transformation lies in the organobase-mediated generation of the acetylide from the 1-bromoalkynes at room temperature. The unique characteristics of DBU as an inherently safer reagent make it an attractive alternative to previous systems wherein required pyrophoric reagents and nonambient temperatures remain unsolved issues. The procedure does not work for the synthesis of alkyl-acetylenes.

DBU‐Mediated Synthesis of Aryl Acetylenes or 1‐Bromoethynylarenes from Aldehydes

“…These results are in accordance with the known dual role of DBU on 1,1-dibromoalkenes 2; as a base it produces 1-bromoalkyne 4, and subsequently it acts as a nucleophile which produces terminal alkyne 3 (Scheme 1). [6] The low yields of terminal alkyne 3 a ( Table 1, entries 1-2) can be rationalized by the reduced nucleophilic activity of DBU (Scheme 1). This reduced activity could be caused by the electrophilic by-product bromotriisopropoxyphosphonium bromide 13 P(O i Pr) 3 Br 2 formed in the Ramirez olefination (Scheme 2).…”

“…Additive NaOH beneficial in not only the exclusive synthesis of terminal alkynes but also for enhancing the rate of reaction to completion in 4 h. In contrast, 16 h is required for the synthesis of terminal alkynes from isolated 1,1-dibromoalkenes without using additive NaOH. [6] Additives NaOH and H 2 O played a pivotal role as a switch for the selective synthesis of terminal alkynes and 1-bromoalkynes, respectively. DBU and additives NaOH and H 2 O are relatively safe reagents compared to pyrophoric reagents such as n-BuLi or Ohira-Bestman reagent for the generation of alkyne functionality.…”

Synthesis via A3 Coupling Reaction of Anthracene‐Propargylamine as a New Scaffold for the Interaction with DNA

“…Compound 2 was treated with 4 equivalents of DBU together with solid KOH in acetonitrile at r.t. for 48 h, giving intermediate 3 with good yield. A possible reaction mechanism comprehends a first elimination reaction forming a bromoalkyne that is subjected to a nucleophilic attack by a second molecule of DBU forming an acetylide that is protonated upon aqueous work‐up …”

“…A possible reaction mechanism comprehends a first elimination reaction forming a bromoalkyne that is subjected to a nucleophilic attack by a second molecule of DBU forming an acetylide that is protonated upon aqueous work-up. [17] The final step for the synthesis of the compounds is reported in Scheme 3 and consists in the Cu(I) iodide-catalyzed A3 coupling reaction between compound 3, formaldehyde and different secondary amines. DMSO was used as a solvent and the reaction reached completion in less than 3 hours with high selectivity and good to high yields for the desired products 4 af.…”

Design, synthesis, and cytotoxic evaluation of novel furo[2,3‐b]quinoline derivatives

“…The synthetic route of compounds 6 is outlined in Scheme 1. [18][19][20][21] According to the novel synthetic method, compound 2 was synthesized from 4-methoxy-benzenamin 1 by treatment with acetic anhydride in dry DCM. 2 was treated with phosphorus oxychloride in dry DMF by refluxing affording 3, and then 3 was treated with carbon tetrabromide and formyl methylene in dry DCM to give 4.…”