Diiodomethane, Simmons-Smith

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]. 

Simmons-Smith reaction of cyclohexene with diiodomethane gives a single cyclopropane product, but the analogous reaction of cyclohexene with 1,1-diiodoethane gives (in low yield) a mixture of two isomeric methyl-cyclopropane products. What are the two products, and how do they differ ... 

The Simmons-Smith reaction has been used as the basis of a method for the indirect a methylation of a ketone. The ketone (illustrated for cyclohexanone) is first converted to an enol ether, an enamine (16-12) or silyl enol ether (12-22) and cyclopropanation via the Simmons-Smith reaction is followed by hydrolysis to give a methylated ketone. A related procedure using diethylzinc and diiodomethane allows ketones to be chain extended by one carbon. In another variation, phenols can be ortho methylated in one laboratory step, by treatment with Et2Zn and... 

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. "... 

Low intensity ultrasound has also been applied to the Simmons-Smith cyclopropanation of olefins with zinc-diiodomethane (237). This reaction normally will not occur without activation of mossy Zn with I2 or Li, and was difficult to scale-up due to delayed initiation. Yields upon sonication are nearly quantitative, activation of the Zn is unnecessary, and no delayed exotherms are observed. In reactions with another class of organic dihalides, ultrasonic irradiation of Zn with a,a -dibromo-o-xylene has proved a facile way to generate an o-xylylene-like species [Eq. (49)],... 

Zinc promoted reactions are responsive to ultrasonic waves. The classic Simmons-Smith reaction was among our first successes(21). Using zinc powder and diiodomethane we obtained good yields of cyclopropanes from styrene and acenaphthene. However, we could not... 

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. 

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. 

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... 

The Simmons-Smith-type cyclopropanation of olefins is one of the most well-known reactions of carbenes and carbenoids. However, cyclopropanation of simple olefins with magnesium carbenoids is usually very difficult and only cyclopropanation of allylic alcohols was reported. Thus, treatment of allylic alcohols (23) in CH2CI2 at —70°C with i -PrMgCl and diiodomethane for 48 to 60 h afforded cyclopropanes in up to 82% yield as a mixture of syn- and and-isomers. In this reaction, 5yn-isomers were mainly or exclusively obtained (synianti = 5 1-400 1) (equation 10). 

Asymmetric cyclopropanation of olefins can also be achieved by the Simmons-Smith reaction (231). Reaction of ( )-cinnamyl alcohol and the diiodomethane-diethylzinc mixed reagent in the presence of a small amount of a chiral sulfonamide gives the cyclopropylcarbinol in up to 75% ee (Scheme 97) (232a). ( )-Cinnamyl alcohol can be cyclopro-... 

Camphor- 10-sulfonic acid, 62 (S)-2-(l-Hydroxy-1-methylethyl)-pyrrolidine, 146 a-Methylbenzylamine, 185 Quina alkaloids, 264 Cycloaddition reactions 2-Oxazolidones, chiral, 225 Cyclopropanation Diiodomethane-Diethylzinc, 276 Simmons-Smith reagent, 275 Deprotonation Lithium amides, chiral, 159... 

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... 

Diiodomethane-Diethylzinc, 276 2-Oxazolidones, chiral, 267 8-Phenylmenthol, 243 (S)-Prolinol, 261 Simmons-Smith reagent, 275 L-Valinol, 341 Amides... 

Organomercury compounds such as ICFbHgl and Hg(CH2Br)2 may be prepared by the reaction of metallic mercury with diiodomethane or by reaction of mercury(II) salts with diazoalkanes. These mercury derivatives are related to the intermediate that has been proposed in the Simmons-Smith reaction, and likewise, they have been found to convert alkenes into cyclopropanes.92... 

The first reaction is deprotection of the alcohol. Benzoate 16 is hydrolyzed with NaOH. What follows is a modified Simmons-Smith cyclopropanation with diiodomethane (41) and diethylzinc i40)... 

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,... 

Cyclopropanation reactions have generated appreciable interest since the products have potential for chemical manipulation and as enzyme inhibitors.60 A notable early finding is that addition at either side of a double bond can be induced by manipulation of the structures of the substrates. For example, compound 171 is obtained from ethyl 4,6-di-0-acetyl-2,3-dideoxy-a-D-eryt/zro-hex-2-enopyranoside by Simmons-Smith cyclopropanation (diiodomethane and Zn-Cu couple) followed by conversion of the C-4 group from an ester to a carbonyl. On the other hand, the substrate with a carbonyl group instead of the ester at C-4 cyclopropanates to give the a-lyxo product 172.198... 

Cyclopropanation of olefins (Simmons-Smith reaction) smoothly proceeds using diethylzinc in combination with diiodomethane. The reaction is much faster with allylic alcohols or its ether derivatives than that with simple olefins. 

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 ... 

While lithium carbenoids have limited applicability in chemistry, an analogous zinc carbenoid, lMuch can be formed by insertion of zinc into diiodomethane, is a reagent in one of the most widely carbenoid reactions in chemistiy—the Simmons-Smith reaction. 

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

---