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Hydromethylation of Unactivated Olefins.

Dao HT, Li C, Michaudel Q, Maxwell BD, Baran PS - J. Am. Chem. Soc. (2015)

Bottom Line: This highly chemoselective method can tolerate labile and reactive chemical functionalities and uses a simple set of reagents.This mild protocol can be used to simplify the synthesis of a specific target or to directly "edit" complex natural products and other advanced materials.The method is also amenable to the simple installation of radioactive and stable labeled methyl groups.

View Article: PubMed Central - PubMed

Affiliation: †Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

ABSTRACT
A solution to the classic unsolved problem of olefin hydromethylation is presented. This highly chemoselective method can tolerate labile and reactive chemical functionalities and uses a simple set of reagents. An array of olefins, including mono-, di-, and trisubstituted olefins, are all smoothly hydromethylated. This mild protocol can be used to simplify the synthesis of a specific target or to directly "edit" complex natural products and other advanced materials. The method is also amenable to the simple installation of radioactive and stable labeled methyl groups.

No MeSH data available.


Diversification of complexmolecules.
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fig2: Diversification of complexmolecules.

Mentions: Where the Fe-mediated hydromethylationreally shines, and is likelyto find widespread application, is in the context of late-stage diversification(Figure 2). For example, Apronal (1s), a hypnotic and sedative drug, could be directly transformed intohydromethylated derivative 2s in 44% yield. Complex naturalproducts such as 1t–v could be hydromethylated,forming 2t–v in synthetically usefulyields. A gram-scale transformation employing rotenone (1t), an active component of an organic insecticide known as derris,highlights the practicality of the current methodology. Next, twonotoriously unstable and sensitive complex natural products were hydromethylated:picrotoxinin12a (1u) and gibberellicacid12b,12c (1v). Both of these highlycongested terpenes, bearing reactive functionalities such as epoxides,free hydroxyl groups, carboxylic acids, strained lactones, and even another olefin, were chemoselectively hydromethylated (asverified by X-ray crystallography). One would be hard pressed to accessthese structures in any other way.


Hydromethylation of Unactivated Olefins.

Dao HT, Li C, Michaudel Q, Maxwell BD, Baran PS - J. Am. Chem. Soc. (2015)

Diversification of complexmolecules.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490774&req=5

fig2: Diversification of complexmolecules.
Mentions: Where the Fe-mediated hydromethylationreally shines, and is likelyto find widespread application, is in the context of late-stage diversification(Figure 2). For example, Apronal (1s), a hypnotic and sedative drug, could be directly transformed intohydromethylated derivative 2s in 44% yield. Complex naturalproducts such as 1t–v could be hydromethylated,forming 2t–v in synthetically usefulyields. A gram-scale transformation employing rotenone (1t), an active component of an organic insecticide known as derris,highlights the practicality of the current methodology. Next, twonotoriously unstable and sensitive complex natural products were hydromethylated:picrotoxinin12a (1u) and gibberellicacid12b,12c (1v). Both of these highlycongested terpenes, bearing reactive functionalities such as epoxides,free hydroxyl groups, carboxylic acids, strained lactones, and even another olefin, were chemoselectively hydromethylated (asverified by X-ray crystallography). One would be hard pressed to accessthese structures in any other way.

Bottom Line: This highly chemoselective method can tolerate labile and reactive chemical functionalities and uses a simple set of reagents.This mild protocol can be used to simplify the synthesis of a specific target or to directly "edit" complex natural products and other advanced materials.The method is also amenable to the simple installation of radioactive and stable labeled methyl groups.

View Article: PubMed Central - PubMed

Affiliation: †Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

ABSTRACT
A solution to the classic unsolved problem of olefin hydromethylation is presented. This highly chemoselective method can tolerate labile and reactive chemical functionalities and uses a simple set of reagents. An array of olefins, including mono-, di-, and trisubstituted olefins, are all smoothly hydromethylated. This mild protocol can be used to simplify the synthesis of a specific target or to directly "edit" complex natural products and other advanced materials. The method is also amenable to the simple installation of radioactive and stable labeled methyl groups.

No MeSH data available.