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. 2024 Mar 18;14(7):4856-4864.
doi: 10.1021/acscatal.3c05444. eCollection 2024 Apr 5.

B(C6F5)3-Catalyzed Dehydrogenation of Pyrrolidines to Form Pyrroles

Ana Alvarez-Montoya  1 , Joseph P Gillions  1 , Laura Winfrey  1 , Rebecca R Hawker  1 , Kuldip Singh  1 , Fabrizio Ortu  1 , Yukang Fu  2 , Yang Li  2 , Alexander P Pulis  1
Affiliations

B(C6F5)3-Catalyzed Dehydrogenation of Pyrrolidines to Form Pyrroles

Ana Alvarez-Montoya et al. ACS Catal. .

Abstract

Pyrroles are important N-heterocycles found in medicines and materials. The formation of pyrroles from widely accessible pyrrolidines is a potentially attractive strategy but is an underdeveloped approach due to the sensitivity of pyrroles to the oxidative conditions required to achieve such a transformation. Herein, we report a catalytic approach that employs commercially available B(C6F5)3 in an operationally simple procedure that allows pyrrolidines to serve as direct synthons for pyrroles. Mechanistic studies have revealed insights into borane-catalyzed dehydrogenative processes.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Dehydrogenation of Pyrrolidines
Scheme 2
Scheme 2. Optimization of B(C6F5)3-Catalyzed Dehydrogenation of Pyrrolidines
Reaction performed with 1a (0.2 mmol). Yields determined by 1H NMR analysis of the crude reaction mixtures with an internal standard. equiv = equivalents. H2·2 = hydrogenated acceptor 2.
Scheme 3
Scheme 3. Scope of the B(C6F5)3-Catalyzed Dehydrogenation of Pyrrolidines
Reaction performed with 1 (0.2 mmol). Yields are determined by 1H NMR analysis of the crude reaction mixtures with an internal standard. All compounds were isolated to confirm identity. Using 1a (3 mmol), isolated yield in parentheses. Using DCE as the solvent at 85 °C. Using p-xylene as the solvent at 120 °C. Using 2a (5 equiv). Reaction performed over 46 h. Using purified (water-free) B(C6F5)3 (20 mol %). Using B(C6F5)3 (40 mol %) and Et3SiH (80 mol %). H2·2a = isobutyltrimethylsilane.
Scheme 4
Scheme 4. B(C6F5)3-Catalyzed Dehydrogenation of Indolines
Reaction performed with 1 (0.2 mmol). Yields are determined by 1H NMR analysis of the crude reaction mixtures with an internal standard.
Scheme 5
Scheme 5. Mechanistic Investigation
Unless otherwise stated, purified B(C6F5)3 (i.e., water-free) was used, and reactions were performed in an Ar glovebox. Isolated yield. Determined by 1H NMR analysis of the crude reaction mixtures with an internal standard. H2O·B(C6F5)3 weighed in air and treated in situ with Et3SiH (40 mol %). Mes = 2,4,6-trimethylphenyl.
Figure 1
Figure 1
Gibbs free energy profiles (in kcal/mol) for the catalytic dehydrogenation of pyrrolidines.
Figure 2
Figure 2
Gibbs free energy profiles (in kcal/mol) for the acceptor versus acceptorless catalytic dehydrogenation of pyrrolidines.
Scheme 6
Scheme 6. Proposed Mechanism
See this image and copyright information in PMC

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