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. 2018 Mar 2;8(3):2006-2011.
doi: 10.1021/acscatal.7b03769. Epub 2018 Jan 18.

3-Aryl-2,5-Dihydropyrroles via Catalytic Carbonyl-Olefin Metathesis

Emilia J Groso  1 , Alexander N Golonka  1 , Ryan A Harding  1 , Brandon W Alexander  1 , Taylor M Sodano  1 , Corinna S Schindler  1
Affiliations

3-Aryl-2,5-Dihydropyrroles via Catalytic Carbonyl-Olefin Metathesis

Emilia J Groso et al. ACS Catal. .

Abstract

Herein, we describe the development of a synthetic strategy towards chiral 3-pyrrolines based on the design principle of iron(III)-catalyzed carbonyl-olefin metathesis. This approach takes advantage of commercially available amino acids as chiral pool reagents and FeCl3 as a Lewis acid catalyst. Our strategy is characterized by its operational simplicity, mild reaction conditions and functional group tolerance. Investigations show that an electron-deficient nitrogen protecting group overcomes limitations arising from competitive binding of the Lewis acid catalyst to unfavorable Lewis basic sites, which ultimately enables catalytic turnover.

Keywords: Lewis acid catalysis; amino acids; carbonyl-olefin metathesis; iron(III) chloride; pyrrolines.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Current approaches towards accessing chiral pyrrolidines.
Figure 2.
Figure 2.
Synthesis of chiral 3-pyrrolines via carbonyl olefin metathesis.
Figure 3.
Figure 3.
Flexible 3-step substrate synthesis from chiral pool reagents.
Figure 4.
Figure 4.
Competitive binding between Lewis basic substrate sites.
Figure 5.
Figure 5.
Selected modifications of chiral 3-pyrroline N-protecting group.
Figure 6.
Figure 6.
Selected modifications of chiral 3-pyrroline products.
See this image and copyright information in PMC

References

    1. For leading references, see: a) Naturally Ocurring Pyrrolizidine Alkaloids; Rizk AFM, Ed.; CRC Press: Boca Raton, FL, 1991; pp 1–240.
    2. b) Mattocks AR Chemistry and Toxicology of Pyrrolizidine Alkaloids; Academic Press: London, 1986; pp 1–393.
    3. c) Bronner SM; Im G-YJ; Garg NK In Heterocycles in Natural Product Synthesis; Majumdar KC; Chattopadhyay SK, Eds.; Wiley-VCH: Weinheim, Germany, 2011; pp 221–265;
    4. d) Michael JP Nat. Prod. Rep 2008, 25, 139–165; - PubMed
    5. e) Michael JP Alkaloids 2001, 55, 91–258. - PubMed
    6. f) Michael JP The Alkaloids, Knölker H-J, Ed.; Academic Press: San Diego, CA, 2016, 75, 1–498. - PubMed
    1. For examples, see: Li X; Li J Mini-Rev. Med. Chem 2010, 10, 794–805. - PubMed
    1. For examples, see: Choi YH; Choi JY; Yang HY; Him YH Tetrahedron Asymmetry 2002, 13, 801–804.
    1. For an example, see: Reisman SE; Doyle AG; Jacobsen EN J. Am. Chem. Soc 2008, 130, 7198–199. - PMC - PubMed
    1. For a review, see: Ellman JA; Owens TD; Tang TP Acc. Chem. Res 2002, 35, 984–995. - PubMed

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