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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.


Direct hydromethylationas a step-economic method.
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fig3: Direct hydromethylationas a step-economic method.

Mentions: To highlight the step-economyof this newly developed C–Cbond-forming methodology, the synthesis of terpene derivative 2w, alkaloid derivative 2x, and norsesquiterpene 2a was demonstrated (Figure 3). Previously, 2w was synthesized in racemic form from crotonaldehyde ina four-step route.13 It can now be synthesizedin an enantiopure form from readily available citronellol (1w) in 68% yield. Hydromethylated quinine analogues such as 2x were previously accessed in a labor-intensive four-step sequence14 but can now be accessed directly in 32% yield.It is noteworthy that tertiary amine and quinoline moieties are toleratedunder the mild reaction conditions. Lastly, the synthesis of 7-desmethyl-2-methoxycalamenene(2a) from the precursor 1a is a testamentto the simplicity of this approach in the context of natural productsynthesis. Indeed, the desired norsesquiterpene 2a wasaccessed in 29% yield, making this synthesis superior in yield andstep count to all prior multi-step approaches (Figure 1A).1


Hydromethylation of Unactivated Olefins.

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

Direct hydromethylationas a step-economic method.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Direct hydromethylationas a step-economic method.
Mentions: To highlight the step-economyof this newly developed C–Cbond-forming methodology, the synthesis of terpene derivative 2w, alkaloid derivative 2x, and norsesquiterpene 2a was demonstrated (Figure 3). Previously, 2w was synthesized in racemic form from crotonaldehyde ina four-step route.13 It can now be synthesizedin an enantiopure form from readily available citronellol (1w) in 68% yield. Hydromethylated quinine analogues such as 2x were previously accessed in a labor-intensive four-step sequence14 but can now be accessed directly in 32% yield.It is noteworthy that tertiary amine and quinoline moieties are toleratedunder the mild reaction conditions. Lastly, the synthesis of 7-desmethyl-2-methoxycalamenene(2a) from the precursor 1a is a testamentto the simplicity of this approach in the context of natural productsynthesis. Indeed, the desired norsesquiterpene 2a wasaccessed in 29% yield, making this synthesis superior in yield andstep count to all prior multi-step approaches (Figure 1A).1

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.