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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.


(A) Direct olefin hydromethylation, an unsolved problemin organicsynthesis. (B) Precedents for hydromethylation. (C) Reaction blueprintwith potential complications.
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fig1: (A) Direct olefin hydromethylation, an unsolved problemin organicsynthesis. (B) Precedents for hydromethylation. (C) Reaction blueprintwith potential complications.

Mentions: The direct, chemoselective hydromethylationof unactivated olefins is a classic unsolved problem of great importancein organic chemistry. This is clearly illustrated in the context ofthe total synthesis of 7-desmethyl-2-methoxycalamenene 2a (Figure 1A).1a,1b To be sure,three different indirect pathways were engineered to accomplish theseemingly simple addition of methane across olefin 1a. In the first approach, a Wacker/Wittig sequence provided intermediate A in low yield. Although the route via B gavean improvement in yield, a toxic mercury reagent was required. Finally,the most frequently used strategy for formal hydromethylation of olefins,employing a Simmons–Smith cyclopropanation and a reductiveC–C bond cleavage (via C), gave an unsatisfactoryyield.1b−1d This Communication reports a solution to this frequentlyencountered issue with the invention of a mild, scalable, and catalyticolefin hydromethylation. This simple method can be used at both theearly and late stages of a synthesis, enabling access to uniquelymodified natural products, medicinally relevant molecules, and evenisotopically labeled structures that would be difficult or impossibleto access in any other way.


Hydromethylation of Unactivated Olefins.

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

(A) Direct olefin hydromethylation, an unsolved problemin organicsynthesis. (B) Precedents for hydromethylation. (C) Reaction blueprintwith potential complications.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: (A) Direct olefin hydromethylation, an unsolved problemin organicsynthesis. (B) Precedents for hydromethylation. (C) Reaction blueprintwith potential complications.
Mentions: The direct, chemoselective hydromethylationof unactivated olefins is a classic unsolved problem of great importancein organic chemistry. This is clearly illustrated in the context ofthe total synthesis of 7-desmethyl-2-methoxycalamenene 2a (Figure 1A).1a,1b To be sure,three different indirect pathways were engineered to accomplish theseemingly simple addition of methane across olefin 1a. In the first approach, a Wacker/Wittig sequence provided intermediate A in low yield. Although the route via B gavean improvement in yield, a toxic mercury reagent was required. Finally,the most frequently used strategy for formal hydromethylation of olefins,employing a Simmons–Smith cyclopropanation and a reductiveC–C bond cleavage (via C), gave an unsatisfactoryyield.1b−1d This Communication reports a solution to this frequentlyencountered issue with the invention of a mild, scalable, and catalyticolefin hydromethylation. This simple method can be used at both theearly and late stages of a synthesis, enabling access to uniquelymodified natural products, medicinally relevant molecules, and evenisotopically labeled structures that would be difficult or impossibleto access 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.