| Autor: |
Corti V; Department of Chemistry, Aarhus University, Aarhus C DK-8000, Denmark., Barløse CL; Department of Chemistry, Aarhus University, Aarhus C DK-8000, Denmark., Østergaard NL; Department of Chemistry, Aarhus University, Aarhus C DK-8000, Denmark., Kristensen A; Department of Chemistry, Aarhus University, Aarhus C DK-8000, Denmark., Jessen NI; Department of Chemistry, Aarhus University, Aarhus C DK-8000, Denmark., Jørgensen KA; Department of Chemistry, Aarhus University, Aarhus C DK-8000, Denmark. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Chemical Society [J Am Chem Soc] 2023 Jan 18; Vol. 145 (2), pp. 1448-1459. Date of Electronic Publication: 2023 Jan 05. |
| DOI: |
10.1021/jacs.2c12750 |
| Abstrakt: |
Chiral eight-membered carbocycles are important motifs in organic chemistry, natural product chemistry, chemical biology, and medicinal chemistry. The lack of synthetic methods toward their construction is a challenge preventing their rational design and stereoselective synthesis. The catalytic enantioselective [4 + 4] cycloaddition is one of the most straightforward and atom-economical methods to obtain chiral cyclooctadiene derivatives. We report the first organocatalytic asymmetric [4 + 4] cycloaddition of 9 H -fluorene-1-carbaldehydes with electron-deficient dienes affording cyclooctadiene derivatives in good yields and with excellent control of peri-, diastereo-, and enantioselectivities. The reaction concept is based on the aminocatalytic formation of a polarized butadiene component incorporated into a cyclic extended π-system, with restricted conformational freedom, allowing for a stereocontrolled [4 + 4] cycloaddition. FMO analysis unveiled that the HOMO and LUMO of the two reacting partners resemble those of butadiene. The methodology allows for the construction of cyclooctadiene derivatives decorated with various functionalities. The cyclooctadienes were synthetically elaborated, allowing for structural diversity demonstrating their synthetic utility for the formation of, for example, chiral cyclobutene- or cyclooctane scaffolds. DFT computational studies shed light on the reaction mechanism identifying the preference for an initial but reversible [4 + 2] cycloaddition delivering an off-cycle catalyst resting state, from which catalyst elimination is not possible. The off-cycle catalyst-bound intermediate undergoes a retro-[4 + 2] cycloaddition, followed by a [4 + 4] cycloaddition generating a cycloadduct from which catalyst elimination is possible. The reaction pathway accounts for the observed peri-, diastereo-, and enantioselectivity of the organocatalytic [4 + 4] cycloaddition. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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