Community hub
Recent from talks
Knowledge base stats:
Talk channels stats:
Members stats:
Simmons–Smith reaction
The Simmons–Smith reaction is an organic cheletropic reaction involving an organozinc carbenoid that reacts with an alkene (or alkyne) to form a cyclopropane. It is named after Howard Ensign Simmons, Jr. and Ronald D. Smith. It uses a methylene free radical intermediate that is delivered to both carbons of the alkene simultaneously, therefore the configuration of the double bond is preserved in the product and the reaction is stereospecific.
Thus, cyclohexene, diiodomethane, and a zinc-copper couple (as iodomethylzinc iodide, ICH2ZnI) yield norcarane (bicyclo[4.1.0]heptane).
The Simmons–Smith reaction is generally preferred over other methods of cyclopropanation, however it can be expensive due to the high cost of diiodomethane. Modifications involving cheaper alternatives have been developed, such as dibromomethane or diazomethane and zinc iodide. The reactivity of the system can also be increased by using the Furukawa modification, exchanging the zinc‑copper couple for diethylzinc.
The Simmons–Smith reaction is generally subject to steric effects, and thus cyclopropanation usually takes place on the less hindered face.[verification needed] However, when a hydroxy substituent is present in the substrate in proximity to the double bond, the zinc coordinates with the hydroxy substituent, directing cyclopropanation cis to the hydroxyl group (which may not correspond to cyclopropanation of the sterically most accessible face of the double bond): An interactive 3D model of this reaction can be seen at ChemTube3D.
Although asymmetric cyclopropanation methods based on diazo compounds (the Metal-catalyzed cyclopropanations) exist since 1966, the asymmetric Simmons–Smith reaction was introduced in 1992 with a reaction of cinnamyl alcohol with diethylzinc, diiodomethane and a chiral disulfonamide in dichloromethane:
The hydroxyl group is a prerequisite serving as an anchor for zinc. An interactive 3D model of a similar reaction can be seen here (java required). In another version of this reaction the ligand is based on salen and Lewis acid DIBAL is added:
The Simmons–Smith reaction can be used to cyclopropanate simple alkenes without complications. Unfunctionalized achiral alkenes are best cyclopropanated with the Furukawa modification (see below), using Et2Zn and CH2I2 in 1,2-dichloroethane. Cyclopropanation of alkenes activated by electron donating groups proceed rapidly and easily. For example, enol ethers like trimethylsilyloxy-substituted olefins are often used because of the high yields obtained.
Despite the electron-withdrawing nature of halides, many vinyl halides are also easily cyclopropanated, yielding fluoro-, bromo-, and iodo-substituted cyclopropanes.
Hub AI
Simmons–Smith reaction AI simulator
(@Simmons–Smith reaction_simulator)
Simmons–Smith reaction
The Simmons–Smith reaction is an organic cheletropic reaction involving an organozinc carbenoid that reacts with an alkene (or alkyne) to form a cyclopropane. It is named after Howard Ensign Simmons, Jr. and Ronald D. Smith. It uses a methylene free radical intermediate that is delivered to both carbons of the alkene simultaneously, therefore the configuration of the double bond is preserved in the product and the reaction is stereospecific.
Thus, cyclohexene, diiodomethane, and a zinc-copper couple (as iodomethylzinc iodide, ICH2ZnI) yield norcarane (bicyclo[4.1.0]heptane).
The Simmons–Smith reaction is generally preferred over other methods of cyclopropanation, however it can be expensive due to the high cost of diiodomethane. Modifications involving cheaper alternatives have been developed, such as dibromomethane or diazomethane and zinc iodide. The reactivity of the system can also be increased by using the Furukawa modification, exchanging the zinc‑copper couple for diethylzinc.
The Simmons–Smith reaction is generally subject to steric effects, and thus cyclopropanation usually takes place on the less hindered face.[verification needed] However, when a hydroxy substituent is present in the substrate in proximity to the double bond, the zinc coordinates with the hydroxy substituent, directing cyclopropanation cis to the hydroxyl group (which may not correspond to cyclopropanation of the sterically most accessible face of the double bond): An interactive 3D model of this reaction can be seen at ChemTube3D.
Although asymmetric cyclopropanation methods based on diazo compounds (the Metal-catalyzed cyclopropanations) exist since 1966, the asymmetric Simmons–Smith reaction was introduced in 1992 with a reaction of cinnamyl alcohol with diethylzinc, diiodomethane and a chiral disulfonamide in dichloromethane:
The hydroxyl group is a prerequisite serving as an anchor for zinc. An interactive 3D model of a similar reaction can be seen here (java required). In another version of this reaction the ligand is based on salen and Lewis acid DIBAL is added:
The Simmons–Smith reaction can be used to cyclopropanate simple alkenes without complications. Unfunctionalized achiral alkenes are best cyclopropanated with the Furukawa modification (see below), using Et2Zn and CH2I2 in 1,2-dichloroethane. Cyclopropanation of alkenes activated by electron donating groups proceed rapidly and easily. For example, enol ethers like trimethylsilyloxy-substituted olefins are often used because of the high yields obtained.
Despite the electron-withdrawing nature of halides, many vinyl halides are also easily cyclopropanated, yielding fluoro-, bromo-, and iodo-substituted cyclopropanes.