Carbene Simmons-Smith reagent

The use of an excess (3 equivalents) of the Simmons-Smith reagent gave exclusively the spiropentane derivatives 618 in 60-70% yield [163a], In contrast, not even trace amounts of these products were observed by using samar-ium-dihalomethane as the carbene source [4b],... 

In contrast to the Simmons-Smith reagent and similar carbenoids, which are reactive and therefore difficult to characterize, adducts of the fV-heterocyclic l,3-diorganylimidazol-2-ylidenes are remarkably stable. The first iV-heterocyclic carbene complex of zinc, namely the l,3-di(l-adamantyl)imidazol-2-ylidene diethylzinc complex 48 (Figure 22), was reported by Arduengo et al. in 1993.98 Because of the general utility of these iV-heterocyclic... 

Nitropropane, 200 Simmons-Smith reagent, 275 Four-membered rings Chromium carbene complexes, 82 Menthol, 172... 

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. 

In the above cycloaddition reactions, carbene is generated in situ. A more convenient way is to use Simmons-Smith reagent ", which transfers methylene from methylene iodide and zinc-copper couple to a carbon-carbon double bond (Scheme 2.56). In the reaction in Scheme 2.56, free carbene is not generated. The intermediate is believed to be ICH2ZnI, which behaves as an electrophile known as carbenoid. 

Many other 1,3-dipolar cycloadditions are known, amongst which is the addition of diazomethane (CH2N2). Expulsion of nitrogen from the adduct leads to the formation of a cyclopropane ring. Another way of achieving the same result involves the addition of a carbene such as the Simmons Smith reagent. This is generated from methylene iodide (CHjIj) and a zinc/copper couple. 

Reaction of CH2I2 with zinc-copper couple forms ICH2Znl, the Simmons-Smith reagent Since the CH2 group is bonded to the metal and does not exist as a free carbene, this intermediate is called a carbenoid. 

The Simmons-Smith reagent (4-33), other carbenoids, and carbenes are very useful in the synthesis of cyclopropanes (see Example 4.25). 

As this stereochemical outcome is comparable to that obtained with the Simmons-Smith reagent or diazomethane in the presence of copper(l) chloride, the intermediacy of carbenes or car-benoids can be assumed. " The exo,anti-product is favored over the xp,5y -compound in both cases. 

With copper(I) chloride as catalyst, 3-anf/-(2-methoxycarbonyl-l-methylethenyl)-cxo-tricyclo[3.2.1.02,4]oct-6-ene (8, R = Me) and 3-an//-[l-(methoxycarbonylmethylene)butyl]-e,xo-tricyclo[3.2.1,02,4]oct-6-ene (8, R = Ph) are isolated in 70 und 60% yield, respectively, and in a ZjE isomeric ratio of 1.3 1 and 1.7 1 after preparative thin layer chromatography.63a,b As this stereochemical outcome is comparable to that obtained with the Simmons-Smith reagent or diazomethane in the presence of copper(l) chloride, the intermediacy of carbenes or car-benoids can be assumed.64 The exo,anti-product is favored over the uxo,sy -compound in both cases. 

No matter how they are generated, carbenes and carbenoids undergo four typical reactions. The most widely used reaction is cyclopropanation, or addition to a TT bond. The mechanism is a concerted [2 + 1] cycloaddition (see Chapter 4). The carbenes derived from chloroform and bromoform can be used to add CX2 to a 7T bond to give a dihalocyclopropane, while the Simmons-Smith reagent adds CH2. Carbenoids generated from diazoalkanes with catalytic Rh(II) or Cu(II) also undergo cyclopropanations. 

Carbenoid (Section 8.14C) A carbene-like species. A species such as the reagent formed when diiodomethane reacts with a zinc-copper couple. This reagent, called the Simmons—Smith reagent, reacts with alkenes to add methylene to the double bond in a stereospecific way. 

The Simmons-Smith reagent (ICH2ZnI) also acts as a carbene source. The reaction between CH2I2 and Zn does not generate a full-fledged free carbene, but instead a carbenoid (Eq. 10.55). A carbenoid is a carbene that is stabilized by complexation to a metal. Even the carbenes created by the reaction between strong bases and haloforms sometimes react as carbenoids, where the carbene is complexed to the counter cation of the strong base. We will examine more carbenoid species in Chapter 12, when alkylidenes and Fischer carbenes are discussed. 

Carbenoid species, such as the Simmons-Smith reagent (Eq. 10.55), undergo facile additions to alkenes to create cyclopropanes. The reactions are stereospecific, making carbenoids synthetically useful versions of carbenes. Carbenoid compounds do not normally perform insertion reactions. 

In another route to cyclopropanes, diiodomethane is treated with zinc powder (usually activated with copper) to generate ICH2ZnI, called the Simmons-Smith reagent This species is an example of a carbenoid, or carbene-like substance, because, like carbenes, it also converts alkenes into cyclopropanes stereospecifically. Use of the Simmons-Smith reagent in cyclopropane synthesis avoids the hazards associated with diazomethane preparation. 

In Summary Diazomethane is a useful synthetic intermediate as a methylene source for forming cyclopropanes from alkenes. Halogenated carbenes, which are formed by dehydro-halogenation of halomethanes, and the Simmons-Smith reagent, a carbenoid arising from the reaction of diiodomethane with zinc, also convert alkenes into cyclopropanes. Additions of carbenes to alkenes differ from other addition processes because a single carbon atom becomes bonded to both alkene carbons. 

Methylene ( CH2), the simplest carbene, can be prepared by decomposition of the highly toxic and explosive reagent diazomethane (CH Nj). However, more easily used reagents have been developed that, while they do not produce methylene directly, function as methylene transfer agents. They are called carbenoid species because they react like carbenes. lodomethylzinc iodide, known as the Simmons-Smith reagent, is a carbenoid. In the Simmons-Smith method, diiodomethane reacts with a zinc-copper alloy to produce an intermediate I—CH Zn—I compound. 

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. 

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. 

There are many ways of generating what appear to be carbenes. But in some cases at least, it seems clear that no free carbene is actually an intermediate instead, a carbenoid (carbene-like) reagent transfers a carbene unit directly to a double bond. For example, in the extremely useful Simmons-Smith reaction... 

The Simmons-Smith reaction seems to be of little value for transfer of an alkoxycarbonyl-carbene to alkenes. Thus, reaction of the reagent formed from ethyl diiodoacetate and zinc-copper couple with 2,5-dimethylhexa-2,4-diene (reflux, 14 days) furnished ethyl 2,2-dimethyl-3-(2-methylprop-l-enyl)cyclopropane-l-carboxylatein only 12% yield, and ethyl dichloroacetate was an even less suitable starting material. ... 

Before we leave this section on cyclopropanes, we want you to take a step back from simply thinking about carbenes, and consider the types of reagents that form three-membered rings generally. They all have something in common, which we could call -enoid character. Cyciopropanes form when a carbene (which, in the singlet state, has an empty, electrophilic p orbital and a full, nominally nucleophilic sp orbital) attacks alkenes. The Simmons-Smith carbenoid is not a carbene, but nonetheless has a carbon atom with joint nucleophilic (alkyl zinc) and electrophilic (alkyl iodide) character. When... 

All disconnections are the same on cyclopropane, requiring a carbene equivalent which will add to an unactivated double bond. Diazomethane will do this, but one of the best carbene sources is CH2I2 with a zinc-copper couple (the Simmons-Smith reaction ). This works particularly well on allylic alcohols (31), no doubt because of hydrogen bonding between the OH group and the reagent. The reaction is then totally stereoselective. 

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