Carbenoids Simmons-Smith reagents

These early studies on zinc carbenoids provide an excellent foundation for the development of an asymmetric process. The subsequent appearance of chiral auxiliary and reagent-based methods for the selective formation of cyclopropanes was an outgrowth of a clear understanding of the achiral process. However, the next important stage in the development of catalytic enantioselective cyclopropanations was elucidation of the structure of the Simmons-Smith reagent. 

Simmons-Smith reagent that contradicts path B, and path A has therefore been widely believed to represent the experimental reality. For lithium carbenoids, on the other hand, the alternative carbometalation/cyclisation pathway has received experimental support. Actually, the factors that determine the... 

The Simmons-Smith Reagent and Related Carbenoid Compounds 337... 

The organization of the material in this chapter is naturally subjective, and certain topics could equally well have been discussed in another section or in a different order. For example, the Simmons-Smith reagent is both an alkylzinc iodide and a carbenoid, and because both sections exist in this chapter, it is discussed under the more specific heading of zinc carbenoids. 

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... 

The carbenoid from Et2Zn/CH2I2 [17], particularly when generated in the presence of oxygen [18], is more reactive than the conventional Simmons-Smith reagents. The milder conditions required are suitable for the preparation of 1-[16, 19] or 2-alkoxy-l-siloxycyclopropanes [20], which are generally more sensitive than the parent alkyl substituted siloxycyclopropanes (Table 2). Cyclopropanation of silyl ketene acetals is not completely stereospecific, since isomerization of the double bond in the starting material competes with the cyclopropanation [19]. 

Fig. 3.16. Two reactions that demonstrate the stereospecificity of n s-cycLopropanations with the Simmons-Smith reagent. In the first reaction the zinc carbenoid is produced according to the original method, and in the second it is produced by the Furukawa variant.

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. 

Usually zinc carbenoids do not insert into olefinic C—H bonds, although the Simmons-Smith reagent was reported to attack ether to give products resulting from insertion of a methylene group into the a-C—H bond 42, 185). As has been mentioned above, the formation of methyl-acetylene derivatives from terminal acetylene derivatives may proceed via insertion of methylene into the C—H bond 528). 

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. 

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). 

The carbenoid generated from diiodomethane/diethylzinc is often found to be more reactive than the conventional Simmons-Smith reagent. Thus, in the case of 1-alkenylboronic acid esters, where diazomethane failed to cyclopropanate trisubstituted derivatives (Section 1.2.1.1.1.) diiodomethane/diethylzinc gave good yields of the required products 16. ... 

Considering the selectivity of this reaction (terminal vs. 1,2-disubstituted alkenes) and the fact that an electron-rich alkene such as isobutyl vinyl ether does not undergo cyclopropanation, it seems that the reactive species formed from the lithiated sulfone and the nickel catalyst does not behave as an electrophilic carbenoid. In this respect, one should note that the Simmons-Smith reagent is electrophilic whereas the methylene transfer reagent arising from treatment of dibromomethane with nickel(O) can achieve cyclopropanation of electron-deficient alkenes only. ... 

The more recently reported route to diethyl 3-oxoalkylhosphonates uses a zinc carbenoid-mediated approach, which is believed to proceed through the intermediacy of a cyclopropylzinc alkoxide. Thus, treatment of simple diethyl 2-oxoaIkylphosphonates with the Furukawa-modifled Simmons-Smith reagent provides a rapid and efficient preparation of 3-oxoalkyIphosphonates. The chain extension of simple, unfunctionalized P-ketophosphonates requires an excess (6 eq) of both Et2Zn and CH2I2 at room temperature. The presence of a-substitution on the 2-oxoalkylphosphonate does not diminish the efficiency of the reaction (see Section 7.2.3.7). 

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. 

Simmons-Smith reagent ICLLZnI. a carbenoid used in cyclopropane synthesis from alkenes. 

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. 

A useful carbenoid is the Simmons-Smith reagent prepared from diiodometh-ane and Zn(Cu). 

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. 

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