Related Experiment Video
Updated: Aug 30, 2025
06:46
Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate
Published on: June 21, 2017
7.5K
Copper Hydride-Catalyzed Enantioselective Olefin Hydromethylation
Yuyang Dong1, Kwangmin Shin1, Binh Khanh Mai2
1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Journal of the American Chemical Society
|August 31, 2022
Summary
This study introduces a new asymmetric hydromethylation method using copper catalysis. It efficiently adds methyl groups to olefins, overcoming limitations of previous methylating reagents.
Area of Science:
- Organic Chemistry
- Catalysis
- Asymmetric Synthesis
Background:
- Enantioselective methylation significantly alters molecular biological properties.
- Asymmetric hydromethylation of olefins is challenging due to reactive methylating agents and limited applicability.
Purpose of the Study:
- To develop a general and efficient asymmetric olefin hydromethylation protocol.
- To utilize methyl tosylate as a compatible methyl source in a reductive reaction environment.
Main Methods:
- Copper hydride (CuH) catalysis was employed for the asymmetric hydromethylation.
- Methyl tosylate was activated in situ to methyl iodide using catalytic iodide.
- Density functional theory (DFT) was used to elucidate the reaction mechanism.
Main Results:
- The protocol demonstrated tolerance for diverse functional groups, heterocycles, and pharmaceutical frameworks.
- Stereoselective hydrocupration followed by a stereoretentive methylation step was observed.
- The methylation proceeds via an SN2-type oxidative addition with methyl iodide.
Conclusions:
- This CuH-catalyzed method provides a versatile approach for asymmetric hydromethylation.
- The use of methyl tosylate and in situ activation offers a practical solution for methyl group installation.
- The mechanistic insights support the development of future asymmetric alkylation strategies.
Related Concept Videos
03:08Hydroboration-Oxidation of Alkenes
8.7K
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
8.7K
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
3.4K
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
3.4K
01:13Olefin Metathesis Polymerization: Overview
2.2K
Recently, the development of olefin metathesis polymerization advanced the field of polymer synthesis. Simply put, the reorganization of substituents on their double bonds between two olefins in the presence of a catalyst is known as the olefin metathesis reaction. The use of metathesis reaction for polymer synthesis is called olefin metathesis polymerization.
Ruthenium-based Grubbs catalyst is the most commonly used catalyst for olefin metathesis polymerization. Grubbs catalyst consists...
Ruthenium-based Grubbs catalyst is the most commonly used catalyst for olefin metathesis polymerization. Grubbs catalyst consists...
2.2K
02:44Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
10.7K
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
10.7K
02:36Oxymercuration-Reduction of Alkenes
7.8K
Oxymercuration–reduction of alkenes is one of the major reactions converting alkenes to alcohols. It involves the hydration of alkenes with mercuric acetate in a mixture of tetrahydrofuran and water, forming an organomercury adduct. This is followed by a demercuration step in which the adduct is reduced to an alcohol using sodium borohydride.
7.8K
02:24Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
8.0K
Introduction
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
8.0K