Simmons-Smith cyclopropanation, olefins

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)],... 

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. 

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. 

From the multitude of synthetic work in the field of cyclopropanation, we will focus on the asymmetric synthesis of cyclopropanes. Besides the known stereocontrolled addition of diazocompounds to olefins (diazo-method) [6] the stereocontrolled Simmons-Smith cyclopropanation has received significant attention in the last ten years. The latter will be discussed further. 

A number of modifications of the original Simmons-Smith cyclopropanation procedure have been reported. Furukawa s reagent, (iodomethyl)zinc derived from diethylzinc and diiodomethane, ° or its modification using chloroiodomethane instead of diiodomethane, ° allows more flexibility in the choice of solvent. The reagent is homogeneous and the cyclopropanation of olefins can be carried out in non-complexing solvents, such as dichloromethane or 1,2-dichloroethane, which greatly increase the reactivity of the zinc carbenoids. 

The first examples of the enantioselective Simmons-Smith cyclopropanations mediated by a chiral catalyst are very recent. Scheme 6.33 shows three catalysts for the cyclopropanation of rrans-cinnamyl alcohol. The most selective appears to be Charette s dioxaborolane (Scheme 6.33c, [120-122], which also affords the highest yield of product, although this procedure is only suitable for small scale.With other olefins, such as cis and trans disubstituted alkenes and P,P-trisubstituted alkenes, the yields are nearly as good and the enantioselectivities are 96-97%. An important finding in this study [120] was that, in addition to the Lewis acid (boron) that binds the alcohol, a second atom to chelate the zinc is also necessary. In the... 

Simmons—Smith Cyclopropanation. Simmons-Smith cyclopropana-tions have been known for many years as an efficient method for cyclopropanation via methylene transfer to olefinic substrates. Although a stoichiometric amount of reagent is mostly required, the superior reactivity and selectivity make the method inseparable from cyclopropanation. The classical Simmons-Smith cyclopropanation involves a zinc carbenoid reagent (IZnCH2l) generated by the oxidative addition of metallic zinc to diiodomethane by a copper metal as an activator (48). This somewhat cumbersome procedure was later replaced by other more easily accessible and reproducible methods. The benchmark replaces the... 

Di-iodomethane reacts with zinc to produce a carbenoid reagent which adds to olefins in the Simmons-Smith cyclopropanation (Fig. 41).23i The reaction is carried out after a preliminary activation of the metal, which can be of low-grade purity ("mossy zinc"). Even if conducted under solvent reflux, i.e., conditions of low-intensity cavitation, the sonochemical procedure offers the advantage of... 

The stereospecific addition of a metal carbenoid (mainly zinc based) to a double bond is known as the Simmons-Smith cyclopropanation. It is one of the most powerful methods of converting olefins to cyclopropanes. 

Simmons-Smith cyclopropanation proceeds via the addition of a zinc carbenoid (6/8) to an olefin. There are three classes of reactions, however, that can generate the reactive zinc species, each with it is own mechanistic pathway. The oxidative addition of an activated form of zinc metal into a C-X bond is by far the most widely used method for the formation of 6... 

OrganometalHc Methods. The Simmons-Smith cyclopropanation procedure has been successfully applied for the first time to the free double bond of the metal-olefin complexes shown in Scheme 12. Product (80) (23%) has the three-membered ring... 

The year 1958 represents a pivotal moment for the cyclopropanation reaction of olefins. At that time, Simmons and Smith at DuPont reported the reaction of diiodomethane and Zn/Cu couple in the presence of olefins to afford cyclopropanes [56]. An important further advance in the Simmons-Smith cyclopropanation reaction resulted from Dauben s observation that cyclo-hex-2-enol underwent syn-selective methenylation [57, 58]. Additionally, the reaction was noted to be accelerated by the resident allylic hydroxyl group in the substrate. As a representative example, treatment of 87 with CH2I2 and Zn/Cu furnished 88 as a single diastereomer moreover, the parent hydrocarbon (4,4,10-trimethyl-A -octalin) failed to react under similar condi-... 

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. "... 

Addition of TCS 14 to CH2l2/Zn, which contains up to 0.04 mol% of lead impurity, improves the Simmons-Smith reaction of olefins such as cyclooctene to give up to 96% of the cyclopropane 2103 [36] (Scheme 13.12). 

Furthermore, cyclopropane structures have often served as intermediates in organic synthesis. For these reasons, olefin cyclopropanation has proved to be a useful tool for synthetic organic chemists. This has led to the development of several methods for cyclopropanation reactions,91 including the metal-catalyzed reactions of diazo compounds with olefins, as well as the Simmons-Smith reaction. 

The transition metal-catalyzed cyclopropanation of alkenes with diazomethane is a valuable alternative to Simmons-Smith methodology [645]. Because of the mild reaction conditions under which this reaction takes place, diazomethane is the reagent of choice if sensitive olefins are to be cyclopropanated [646-648]. 

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-... 

Cyclopropanes are commonly synthesized with Zn(CH2I)2 (37) using the Simmons-Smith-reactum.16 This reaction proceeds via one-step addition of one of the methylene groups of the zinc reagent to olefins. As an advantage of the Simmons-Smith-reaction no free carbene is involved. 

Electrochemical cyclopropanation of alkenes occurs using dibromomethanes at a sacrificial zinc electrode in a CH2C12/DMF mixture with a one compartment cell (equation 65). Yields using more than twenty isolated and conjugated olefins were generally good (30 to 70%)98. Benzal halides give only poor yields in the same reaction, but 2,2-dibromo-propane leads to the equivalent gem-dimethylcyclopropanes in fair yields. The method represents a useful alternative to other methods of cyclopropanation of olefins such as the Simmons-Smith reaction. 

The Simmons-Smith reaction is a powerful method for preparing cyclopropanes from olefins using zinc carbenoids (IZnCH2I, EtZnCH2I, Zn(CH2X)2).7a,278,278a A variety of versions of this reaction have been developed and new carbenoids species have been made. For recent reviews, see Ref 279 and 279a. 

Polymerization. Monomers. The cyclopropane type monomers are prepared either by addition of the dichlorocarbene or by the Simmons-Smith reaction on the corresponding olefins. Most of these compounds have been described. Spiropentane is prepared by the Applequist method (I, 2), by the reaction of zinc with C(CH2Br)4 in alcohol in the presence of ethylenediaminetetraacetic acid (EDTA). This hydrocarbon is purified until a single NMR signal is obtained at t = 9.28. 

---