Carbenes and carbenoids

Yields in Simmons-Smith reactions are sometimes low. Nevertheless, since it often provides the only feasible route to a particular cyclopropane derivative, it is a valuable addition to the organic chemist s store of synthetic methods. 

It is clear that free CH2 is not involved in the Simmons-Smith reaction, but there is substantial evidence to indicate that carbenes are formed as intermediates in certain other reactions that convert aUcenes to cyclopropanes. The most studied examples of these reactions involve dichlorocarbene and dibromocarbene. 

Carbenes are too reactive to be isolated and stored, but have been trapped in frozen argon for spectroscopic study at very low temperatures. 

Dihalocarbenes are formed when trihalomethanes are treated with a strong base, such as potassium fert-butoxide. The trihalomethyl anion produced on proton abstraction dissociates to a dihalocarbene and a halide anion  

When generated in the presence of an alkene, dihalocarbenes undergo cycloaddition to the double bond to give dihalocyclopropanes  

What alkenes would you choose as starting materials in order to prepare each of the following cyclopropane derivatives by reaction with iodomethylzinc iodide  

Sample Solution (a) In a cyclopropane synthesis using the Simmons-Smith reagent, you should remember that a CH2 unit is transferred. Therefore, retrosynthetically disconnect the bonds to a CH2 group of a three-membered ring to identify the starting alkene. 

Cyclopropanation of alkenes with the Simmons-Smith reagent bears some similarity to epoxidation. Both reactions are stereospecific cycloadditions, and iodomethylzinc iodide behaves, like peroxy acids, as a weak electrophile. Both cycloadditions take place faster with more highly substituted double bonds than less substituted ones, but are sensitive to steric hindrance in the alkene. These similarities are reflected in the mechanisms proposed for the two reactions shown in Mechanism 14.2. Both are believed to be concerted. 

Iodomethylzinc iodide breaks the pattern we have seen so far in organometallic reactivity. Unlike organolithium, Grignard, and organocopper reagents, all of which are nucleophilic, iodomethylzinc iodide is electrophilic. 

Iodomethylzinc iodide is often referred to as a carbenoid, meaning that it resembles a carbene in its chemical reactions. Carbenes are neutral molecules in which one of the carbon atoms has six valence electrons. Such carbons are divalent they are directly bonded to only two other atoms and have no multiple bonds. Iodomethylzinc iodide reacts as if it were a source of the carbene H — C — H. 

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The synthesis of aziridines through reactions between nitrenes or nitrenoids and alkenes involves the simultaneous (though often asynchronous vide supra) formation of two new C-N bonds. The most obvious other alternative synthetic analysis would be simultaneous formation of one C-N bond and one C-C bond (Scheme 4.26). Thus, reactions between carbenes or carbene equivalents and imines comprise an increasingly useful method for aziridination. In addition to carbenes and carbenoids, ylides have also been used to effect aziridinations of imines in all classes of this reaction type the mechanism frequently involves a stepwise, addition-elimination process, rather than a synchronous bond-forming event. 

The Addition of Carbenes and Carbenoids to Double and Tripie Bonds... 

Carbenes and carbenoids can add to double bonds to form cyclopropanes or insert into C-H bonds. 

Hydride and 1,2-alkyl shifts represent the most common rearrangement reactions of carbenes and carbenoids. They may be of minor importance compared to inter-molecular or other intramolecular processes, but may also become the preferred reaction modes. Some recent examples for the latter situation are collected in Table 23 (Entries 1-10, 15 1,2-hydride shifts Entries 11-15 1,2-alkyl shifts). Particularly noteworthy is the synthesis of thiepins and oxepins (Entry 11) utilizing such rearrangements, as well as the transformations a-diazo-p-hydroxyester - P-ketoester (Entries 6, 7) and a-diazo-p-hydroxyketone -> P-diketone (Entry 8) which all occur under very mild conditions and generally in high yield. 

As a tool to improve the regio- and stereoselectivity of C-H insertion, activation of a specific C-H bond of substrates to be inserted seems to be appropriate in conjunction with the manipulation of carbene character. These two tools for the improvement of insertion selectivity will provide us with useful tools of the C-C bond formation by carbenes and carbenoids. 

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

Carbenes and carbenoids can add to double bonds to form cyclopropanes or insert into C—H bonds. These reactions have very low activation energies when the intermediate is a free carbene. Intermolecular insertion reactions are inherently nonselective. The course of intramolecular reactions is frequently controlled by the proximity of the reacting groups.53... 

Fluoroalicyclic derivatives, of metals and metalloids, 15 323-374 chemical properties of, 15 342-343 coordination complexes, 15 346-368 biligate bimetallic, 15 356-363 chelate, 15 351-356 decomposition products, 15 366-368 monoligate, 15 347-351 triligate bimetallic, 15 363-366 modification of, 15 340-341 physical properties, of, 15 345-346 preparative methods for, 15 324-341 carbene and carbenoid additions, 15 324-325... 

Carbenes and carbenoids have long been recognized as a highly reactive species and are frequently used as intermediates in organic synthesis. From a synthetic perspective, however, most of the carbenes are relatively short-lived and are too reactive to be controlled. Recently, metal-carbene complexes (or metaUocarbenes) were found to be easier to control and are nowadays widely used in organic synthesis . 

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). 

The carbon-hydrogen insertion (C,H insertion) is one of the most striking reactions of carbenes and carbenoids. The reaction is interesting and very useful for the construction... 

Some monographs and reviews concerning carbenes and carbenoids ... 

For a monograph, see Johnson Ylid Chemistry, Academic Press New York. 1966. For reviews, sec Morris. Surv. Prog. Chem. 1983, 10, 189-257 Hudson Chem. Br. 1971, 7, 287-294 Lowe Chem. Ind. (London) 1970, 1070-1079. For a review on the formation of ylides from the reaction of carbenes and carbenoids with heteroatom lone pairs, see Padwa Hornbuckle Chem. Rev. 1991, 91, 263-309. 

For reviews of the stereochemistry of carbene and carbenoid addition to double bonds, see Moss Set. Org. Transform. 1970, /, 35-88 Closs Top Stereochem. I960 3, 193 235. For a discussion of enantioselectivity in this reaction, see Nakamura Pure App. Ckem. 1978,50, 37. 

Many crystallographic structures of these carbenes and carbenoids has been solved, indicating (1) they are true carbenes with little ylidic character thus the contribution of ionic structures (175b) is relatively small in comparison with (175a) (2) small N-C-N angles at the carbene center (101-102°) in comparison with typical values (108.5-109.7°) for the corresponding angle in imidazolium salts ... 

A. Cyclopropanation of Carbon-Carbon Multiple Bonds with Carbenes and Carbenoids... 

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