Elsevier

Tetrahedron Letters

Volume 60, Issue 3, 17 January 2019, Pages 327-330
Tetrahedron Letters

Metal-free one-pot three-step process for the direct conversion of aryl alkynes into secondary amines with TfOH/B2(OH)4

https://doi.org/10.1016/j.tetlet.2018.12.041Get rights and content

Highlights

Abstract

A metal-free one-pot synthesis of secondary amines from aryl alkynes via hydration-condensation-reduction three-step process in the presence of TfOH and B2(OH)4 has been developed. A series of secondary amines were obtained with good functional group tolerance and satisfied yields.

Introduction

Transformation of alkynes into valuable amine compounds is very useful in organic synthesis due to the readily availability of various alkynes and wide utility of amines [1], [2]. For example, the drugs like Crispin A [3], (+)-terreusinone [4], and (−)-epimyrtine [5] could be prepared from alkynes via reductive hydroamination (Fig. 1). However, the metal complex catalysts are necessary in the reductive hydroamination of alkynes [6], [7], which restrains its application in the preparation of pharmaceuticals due to the residue of metals. Therefore, it is highly desirable to develop metal-free, atom-, step-, and pot-economic methods to prepare amines from alkynes.

Another protocol for the preparation of amines from alkynes is hydration-condensation-reduction three-step process. The hydration of alkynes was well-developed with various metal complexes [8] or BrØnsted acids as catalysts [9] under harsh conditions. Recently, Li and co-workers reported a metal-free hydration of alkynes catalyzed by trifluoromethanesulfonic acid (TfOH) in trifluoroethanol (TFE) under mild conditions [10], which is suitable for sequential reaction. For example, our group have developed a one-pot two-step process to convert alkynes into chiral alcohols via TfOH-catalyzed hydration and ruthenium-catalyzed asymmetric reduction in TFE under mild conditions [11]. Inspired by the above-mentioned works, we speculated that TfOH could be used as a catalyst not only for the hydration of alkynes in TFE, but also for the sequential condensation between amines and in situ generated ketones to form imines. And then a metal-free one-pot three-step process for the direct conversion of aryl alkynes into secondary amines will be realized with a suitable non-metallic reducing agent for the subsequent reduction of imines.

In 2016, Stokes reported a pioneering palladium-catalyzed B2(OH)4-mediated transfer hydrogenation of unsaturated C–C bonds with water as a hydride donor [12]. Since then, the boron agents have been widely used in hydrogen transfer reaction due to its environmentally benign, safety and cost-efficiency [13]. For example, a B2(OH)4-mediated expeditious hydrogenation of N-heterocycles with water as hydrogen sources under metal-free conditions was achieved by Wu’s group [14]. In addition, our group reported a one-pot synthesis of tetrahydroquinoxalines from 2-amino(nitro)anilines and 1,2-dicarbonyl compounds promoted by B2(OH)4 in water [15]. Presumably, B2(OH)4 will be a promising metal-free reducing agent for the reduction of imines.

As shown in Scheme 1, we represent herein a metal-free one-pot three-step sequential reaction for direct conversion of alkynes into secondary amines through TfOH-catalyzed alkyne-to-ketone hydration and ketone-to-imine condensation, followed by B2(OH)4-mediated reduction of imines.

Section snippets

Results and discussion

The study of one-pot three-step sequential reaction converting alkynes into amines was commenced by hydration of phenylacetylene (1a) with 20 mol% TfOH as a catalyst in TFE in the presence of 2 equivalents of water at 40 °C for 6 h. Next, aniline (2a) was added and kept stirring for 1 h, the subsequent reduction was promoted by a certain amount of boron agents at 80 °C for 6–18 h. As shown in Table 1, the yield of 3a reached to 65% after treatment by B2(OH)4 in TFE for 6 h (entry 1). By

Conclusion

In summary, we have developed a metal-free one-pot conversion of alkynes into secondary amines through hydration-condensation-reduction sequential reaction with TfOH/B2(OH)4 in TFE. This process has a great potential for practical application in drug synthesis due to convenient operation and avoiding isolation and purification of intermediates. A possible reaction pathway was also proposed.

Acknowledgments

We are grateful for financial support from Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University (NPRD 2018007).

References (15)

  • J. Li et al.

    Green Chem.

    (2013)
  • W. Liu et al.

    Org. Lett.

    (2016)
  • S. Liu et al.

    Org. Lett.

    (2018)
    H. Liu et al.

    RSC Adv.

    (2018)
  • Y.T. Xia et al.

    Chem.-A Eur. J.

    (2016)
  • B.A. Trofimov et al.

    Acc. Chem. Res.

    (2018)
    K.I. Galkin et al.

    Russ. Chem. Rev.

    (2016)
    R. Salvio et al.

    Asian J. Org. Chem.

    (2014)
    R. Chinchilla et al.

    Chem. Rev.

    (2014)
    I.T. Trotuş et al.

    Chem. Rev.

    (2014)
  • L.J. Gooßen et al.

    Chem. Rev.

    (2015)
  • H.J. Knölker et al.

    Tetrahedron Lett.

    (2005)
There are more references available in the full text version of this article.

Cited by (9)

View all citing articles on Scopus
View full text