Lewis Acid-Promoted Three-Component Reactions of Propargylic Alcohols with 2-Butynedioates and Secondary Amines

Abstract

We report herein a three-component reaction of propargylic alcohols with 2-butynedioates and secondary amines, which furnished functionalized dihydroazepines. In the cases where benzylmethylamine and benzyl-i-propylamine were used as the secondary amine, the reaction afforded 2,5-dihydro-1H-pyrroles and 2,3-dihydro-1H-pyrroles, respectively, as the major product along with the desired dihydroazepines. The reaction mode depends on the electronic and steric effect of the substitutents on the secondary amines used. A tentative mechanism for this cascade process is postulated. The key intermediate is ascribed to 1,3,4-pentatrien-1-amine, which is formed by trapping the in situ generating allenic carbocation with enamine. Because of the reactivity of 1,3,4-pentatrien-1-amine formed, different products were thus formed.

Recent Advances in the Synthesis of Heterocyclics via Cascade Cyclization of Propargylic Alcohols

“…In 2011, Wang and co‐workers reported a BF 3 ⋅Et 2 O‐promoted three‐component reaction of readily available propargylic alcohols 1 with 2‐butynedioates 25 and secondary amines 26 , which leading to functionalized dihydroazepines 28 in moderate to good yields (Scheme 10). [18] It was worth noting that other types of products were also found depending on the electronic and steric effect of the substituents on the amines. When secondary amines benzylmethylamine and benzyl‐ i ‐propylamine were used as nucleophiles, the dihydro‐1 H ‐pyrroles ( 29 and 30 ) were obtained along with the desired dihdroazepines.…”

Scope and advances in the catalytic propargylic substitution reaction

“…The use of BF 3 $Et 2 O as a Lewis acid catalyst for propargylic substitution was again demonstrated by Wang and co-workers in the year 2011 for the synthesis of functionalized dihydroazepines 52 by a three-component reaction between propargylic alcohols 39, 2-butynedioates 50 and secondary amines 51, Scheme 18. 48 The key step is ascribed to the reaction of the in situ generated enamine 51a with allenic intermediate formed from the propargylic alcohol. Several catalysts like ZnCl 2 , FeCl 3 , or I 2 were tested and BF 3 $Et 2 O gave the best result yield among all the catalysts.…”

“…The use of BF 3 ·Et 2 O as a Lewis acid catalyst for propargylic substitution was again demonstrated by Wang and co-workers in the year 2011 for the synthesis of functionalized dihydroazepines 52 by a three-component reaction between propargylic alcohols 39, 2-butynedioates 50 and secondary amines 51, Scheme 18 . 48 …”

Synthesis of dihydrobenzofurans and dihydroindoles by intramolecular Friedel-Crafts reaction of aryloxy- and arylamino-substituted propargylic alcohols

“…The allenes generated in situ could then undergo various cascade reactions to form many useful structural frameworks. [20][21][22][23][24][25][26] In a recent report, the Zhou group have developed an intramolecular Friedel-Crafts (IFC) reaction that provides a facile and versatile method for one-step construction Very recently, our group has reported the application of propargylic alcohols for the construction of substituted fluorenes, in which five-membered rings were constructed by IFC reactions. 29 It was envisaged that the similar IFC reaction of propargylic alcohols may also be applied to construct a five-membered heterocyclic skeleton.…”