Couple-close: Unified approach to semisaturated cyclic scaffolds.
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| Title: | Couple-close: Unified approach to semisaturated cyclic scaffolds. |
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| Authors: | Xie, Jiaxin (AUTHOR), Zhao, William Y. (AUTHOR), Wang, Johnny Z. (AUTHOR), Lyon, William L. (AUTHOR), Takanashi, Noriyuki (AUTHOR), Long, Alice (AUTHOR), Sodano, Taylor M. (AUTHOR), Kelly, Christopher B. (AUTHOR), Bryan, Marian C. (AUTHOR), MacMillan, David W. C. (AUTHOR) |
| Source: | Science. 1/22/2026, Vol. 391 Issue 6783, p399-406. 8p. |
| Subjects: | Organic synthesis, Chemical synthesis, Ring formation (Chemistry), Aromatic compounds, Bicyclic compounds |
| Abstract: | Couple-close as a synthetic paradigm has the potential to change the way that synthetic organic chemists approach cyclic scaffold construction. One class of cyclic molecules that has been increasingly sought after is semisaturated cyclic scaffolds, whose specific blend of Csp2- and Csp3-hybridized components confers distinct properties to these species. However, existing methods to construct these scaffolds are limited, often relying on arene saturation or annulations that require lengthy de novo syntheses. Herein, we describe a unified and highly modular couple-close strategy for the synthesis of semisaturated scaffolds. This approach installs bifunctional linkers onto aromatic rings through a range of bond-forming reactions, and subsequent cyclization furnishes semisaturated bicyclic adducts. Key to this approach is a mechanistically distinct cobalt-catalyzed dehydrogenative radical cyclization that proceeds efficiently even on electronically unbiased arenes, enabling a broad substrate scope under mild reaction conditions. Editor's summary: Many of the most efficient reactions currently used in pharmaceutical research link together flat molecular fragments. Finding ways to diversify structures in the third dimension is thus a burgeoning area of research. Xie et al. report a versatile method of fusing flat aromatic rings to nonplanar saturated counterparts. After tethering one end of the saturated backbone to the aromatic cycle, the authors used a cobalt catalyst together with a photoredox catalyst to close the second ring, releasing hydrogen as a by-product. —Jake S. Yeston [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Couple-close as a synthetic paradigm has the potential to change the way that synthetic organic chemists approach cyclic scaffold construction. One class of cyclic molecules that has been increasingly sought after is semisaturated cyclic scaffolds, whose specific blend of Csp2- and Csp3-hybridized components confers distinct properties to these species. However, existing methods to construct these scaffolds are limited, often relying on arene saturation or annulations that require lengthy de novo syntheses. Herein, we describe a unified and highly modular couple-close strategy for the synthesis of semisaturated scaffolds. This approach installs bifunctional linkers onto aromatic rings through a range of bond-forming reactions, and subsequent cyclization furnishes semisaturated bicyclic adducts. Key to this approach is a mechanistically distinct cobalt-catalyzed dehydrogenative radical cyclization that proceeds efficiently even on electronically unbiased arenes, enabling a broad substrate scope under mild reaction conditions. Editor's summary: Many of the most efficient reactions currently used in pharmaceutical research link together flat molecular fragments. Finding ways to diversify structures in the third dimension is thus a burgeoning area of research. Xie et al. report a versatile method of fusing flat aromatic rings to nonplanar saturated counterparts. After tethering one end of the saturated backbone to the aromatic cycle, the authors used a cobalt catalyst together with a photoredox catalyst to close the second ring, releasing hydrogen as a by-product. —Jake S. Yeston [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.aec5748 |
