Zinc-copper, Simmons-Smith

Propargylic copper/zinc reagents Reaction of alkynylcoppcrs with iodomcthyl-zinc iodide (Simmons-Smith reagent) provides propargylic copper/zinc reagents, which react with aldehydes or ketones to form homopropargylic alcohols in 80-95% yield. 

Simmons-Smith reagent Named after the duPont chemists who discovered that diiodo-mechane would react with an active zinc-copper couple in ether to give a reagent with molecular formula ICHiZnl. The reagent adds stereospecifically cis- to alkenes to give cyclopropanes in high yields. 

In 1958 Simmons and Smith described a new and general synthesis of cyclopropanes by treatment of olefins with a reagent prepared from methylene iodide and a zinc-copper couple in ether solution. 

Without question, the most powerful method for cyclopropane formation by methylene transfer is the well-known Simmons-Smith reaction [6]. In 1958, Simmons and Smith reported that the action of a zinc-copper couple on diiodomethane generates a species that can transform a wide variety of alkenes into the corresponding cyclopropanes (Scheme 3.3) [7]. 

A carbene, R2C , is a neutral molecule containing a divalent carbon with only six valence electrons. Carbenes are highly reactive toward alkenes, adding to give cyclopropanes. Nonlialogenated cyclopropanes are best prepared by treatment of the alkene with CH212 and zinc-copper, a process called the Simmons-Smith reaction. 

The cyclopropanation of 1-trimethylsilyloxycyclohexene in the present procedure is accomplished by reaction with diiodomethane and diethylzinc in ethyl ether." This modification of the usual Simmons-Smith reaction in which diiodomethane and activated zinc are used has the advantage of being homogeneous and is often more effective for the cyclopropanation of olefins such as enol ethers which polymerize readily. However, in the case of trimethylsilyl enol ethers, the heterogeneous procedures with either zinc-copper couple or zinc-silver couple are also successful. Attempts by the checkers to carry out Part B in benzene or toluene at reflux instead of ethyl ether afforded the trimethylsilyl ether of 2-methylenecyclohexanol, evidently owing to zinc iodide-catalyzed isomerization of the initially formed cyclopropyl ether. The preparation of l-trimethylsilyloxybicyclo[4.1.0]heptane by cyclopropanation with diethylzinc and chloroiodomethane in the presence of oxygen has been reported. "... 

Cyclopropanation with Halomethylzinc Reagents. A very effective means for conversion of alkenes to cyclopropanes by transfer of a CH2 unit involves reaction with methylene iodide and a zinc-copper couple, referred to as the Simmons-Smith reagent.169 The reactive species is iodomethylzinc iodide.170 The transfer of methylene occurs stereospecifically. Free CH2 is not an intermediate. Entries 1 to 3 in Scheme 10.9 are typical examples. 

Lack of cooling during preparation of the Simmons-Smith organozinc reagent caused the reaction to erupt. The possibly pyrophoric nature of organozinc compounds and the presence of ether presents a severe fire hazard [1]. An alternative, safer method of activating the zinc for the reaction involves use of ultrasonic irradiation rather than the copper-zinc couple [2]. 

The direct reaction of zinc metal with organic iodides dates back to the work of Frankland(67). Several modifications have been suggested since that time to increase the reactivity of the metal. The majority of these modifications have employed zinc-copper couples(68-72), sodium-zinc alloys(73), or zinc-silver couples(77). Some recent work has indicated that certain zinc-copper couples will react with alkyl bromides to give modest yields of dialkylzinc compounds(74,73). However, all attempts to react zinc with aryl iodides or bromides have met with failure. The primary use of zinc couples has been in the Simmons-Smith reaction. This reaction has been primarily used with diiodomethane as 1,1-dibromides or longer chain diiodides have proven to be too unneactive even with the most reactive zinc couples. 

H. E. Simmons and R. D. Smith of the DuPont Company had developed a useful cyclopropane synthesis by reacting a zinc-copper couple with an alkene. 

Zinc/copper couple (Zn/Cu), produced by the treatment of zinc with HC1, followed by the addition of copper(n) sulfate, has been known since the seminal work of Simmons and Smith.67 A less reactive form of activated zinc, but one that is sufficiently active for most applications, is produced by the treatment of the metal with 1,2-dibro-moethane, followed by Me3SiCl.68 The most reactive form of activated zinc, the so-called Rieke zinc (Zn ), is finely divided metallic zinc produced by the homogenous reduction of zinc halides in THF.69... 

Among methods of preparing optically active cyclopropane compounds, the Simmons-Smith reaction, first reported in 1958, is of significance. This reaction refers to the cyclopropanation of alkene with a reagent prepared in situ from a zinc-copper alloy and diiodomethane. The reaction is stereospecific with respect to the geometry of the alkene and is generally free from side reactions in contrast to reactions involving free carbenes. 

In the Simmons-Smith reaction, the purpose of copper is simply to activate the Zn surface and has no other role. Iodomethyl zinc behaves as a weak nucleophile. As generally expected, the presence of an ally lie oxygen gives a large rate enhancement, and more remote neighboring oxygen atoms also influence the stereochemical course of the reaction. 

The Simmons-Smith reaction " and its variants are widely used for the stereospecific synthesis of cyclopropane compounds. The methodology involves the use of copper-treated zinc metal (the zinc-copper couple) with diiodomethane to add methylene to a carbon-carbon double bond. Alternative use of diazomethane in catalytic reactions does not offer the same synthetic advantages and is usually avoided because of safety considerations. As significant as is the Simmons-Smith reaction for cyclopropane formation, its employment for organic synthesis was markedly advanced by the discovery that allylic and homoallylic hydroxyl groups accelerate and exert stereochemical control over cyclopropanation of alkenes (e.g, Eq. 21), and this acceleration has been explained by a transition state model... 

A branched-chain iodo sugar derivative, l,5-anhydro-4,6-0-benzyl-idene-2,3-dideoxy-3-C-(iodomethyl)-D-rifoo-hex-l-enitol [4,6-O-ben-zylidene-3-deoxy-3-C-(iodomethyl)-D-allal] (200), is one of the products formed on treatment of methyl 4,6-0-benzylidene-2,3-dideoxy-a-D-en/thro-hex-2-enopyranoside (77) with the Simmons-Smith reagent (diiodomethane and zinc-copper couple).123,212 Compound 200 displays high solvolytic reactivity, an observation that has been rationalized by supposing the formation of the highly stabilized carbonium ion213 (201). Thus, under conditions wherein methyl 2,3,4-tri-0-acetyl-6-deoxy-6-iodo-a-D-glucopyranoside required more than 24 hours to react appreciably with an excess of silver nitrate in 50% aqueous p-dioxane buffered with silver carbonate, the iodide 200 was hydrolyzed completely in less than 1 minute the product of hydrolysis of 200 is the cyclopropyl aldehyde 202. Methanolysis of... 

Reduction of alkynes to alkenes. The zinc-copper couple of Smith and Simmons (1, 1292) reduces internal alkynes to (Z>alkcncs exclusively in yields generally >95%.2 Terminal alkynes are reduced to 1-alkenes.3 Example ... 

Sulfur-stabilized copper-zinc carbanions have been used [299] by Knochel et at A first type obtained from the reaction of the Simmons-Smith reagent with a copper(i) thiolate was treated with a... 

Trimethylamine N-oxide, 325 Vinyltrimethylsilane, 343 Other reactions (Phenylsulfonyl)allene, 247 Cyclodehydration Diethoxytriphenylphosphorane, 109 Hexamethylphosphoric triamide, 142 Cycloprop anation Simmons-Smith reaction Diiodomethane-Diethylzinc, 276 Simmons-Smith reagent, 275 by other reagents which add CH2 to a carbon-carbon multiple bond Dibromomethane-Zinc-Copper(I) chloride, 93... 

The Simmons-Smith cyclopropanation utilizes methylene diiodide and a zinc-copper couple to produce a carbenoid intermediate. This intermediate reacts with olefins to give cyclopropanes. The geometry of the double bond is preserved in file cyclopropane. 

Diiodomethane with zinc-copper couple is a particularly good reagent for the insertion of a methylene group into an olefinic bond. The reaction is known as the Simmons-Smith procedure,10 and is likely to proceed as follows ... 

Conia and his co-workers144 modified the Simmons-Smith reaction145,146 by using enol ether plus predominantly diiodomethane/zinc-silver couple instead of the common known diiodomethane/zinc-copper couple147. This method is an excellent access to cyclopropanols and related compounds148 149 (Scheme 29). Furthermore,... 

Allylcopper/zinc reagents can be prepared directly by reaction of vinyl copper reagents with (iodomethyl)zinc iodide, the Simmons-Smith reagent. These allylcopper/zinc reagents do not couple with an alkyl iodide or benzyl bromide, but react readily with electrophiles such as aldehydes, ketones, or imines.3 This approach to organodimetallic reagents is apparently limited (see Iodomethylzinc iodide, this volume). 

The bifunctional cyclopropane 156 was also prepared by modified Simmons-Smith cyclopropanation 85) of 2-trimethylsilyl-2-propen-l-ol 157 84) followed by oxidation of the cyclopropylcarbinol 158 with activated manganese dioxide 88 >, in 72% overall yield, Eq. (50) 86,89). Coupling of the aldehyde 156 with 2,6-dimethylcyclohexenone 159 90) induced by the low valent titanium reagent from TiCl3 and zinc-copper couple (or lithium metal) provided the silylated cyclopropyldiene 160, in 50-60% yield, Eq. (51) 89 91>. 

Another reaction that builds a cyclopropane ring onto a carbon-carbon double bond is called the Simmons-Smith reaction. This reaction does not actually involve a car-bene, but rather a carbenoid, an organometallic species that reacts like a carbene. This species is generated by reaction of diiodomethane with zinc metal from a special alloy of zinc and copper ... 

The Simmons-Smith reagent, named for the two DuPont chemists who discovered it, is made by adding methylene iodide to the zinc-copper couple (zinc dust that has been activated with an impurity of copper). The reagent probably resembles iodomethyl zinc iodide, ICH2ZnI. This kind of reagent is called a carbenoid because it reacts much like a carbene, but it does not actually contain a divalent carbon atom. 

Diiodomethane, CH2I2 Reacts with alkenes in the presence of zinc-copper couple to yield cyclopropanes (Simmons-Smith reaction Section 7.6). 

Simmons-Smith reaction (Section 7.6) a method for preparing a cyclopropane by treating an alkene with diiodomethane and zinc-copper. 

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