Carbene reaction

Structurally, a carbene is the smallest member of the alkene family. As carbenes have no charge, they are expected to have a certain stability toward water. In fact, in some of the earMest work, carbenes were generated in aqueous medium under biphasic conditions via the reaction of chloroform with a strong base such as NaOH. 

Tebbe s Reagent Cp2Ti=CH2 (Eq. 11.33) has been applied to the synthesis of A -capnellane by Stille and Grubbs (Eq. 14.90). In the key steps, 14.22 is converted to 14.23 by a metathesis-like rearrangement followed by an ester group trapping the titanacarbene. 

Many of the early metathesis catalysts were not very tolerant of organic functionality, but newer catalysts are more tolerant and should make metathesis a more commonly used reaction in organic synthesis. 

Rhodium Acetate Catalyzed Carbene Reactions Another reaction involving a metal carbene is illustrated by Equation 14.91, where Rh2(OAc)4 is the catalyst. A diazoketone acts as a source of a carbene that inserts into an activated C—H bond. The presumed intermediate rhodium carbene complex is too unstable to isolate. 

We can confidently predict that the whole area of organometallic chemistry in organic synthesis will continue to grow strongly. It is likely that transition metal reagents will be involved in many of the new organic synthetic methods to be developed in the next few years. 

Seebach, Angew. Chem., Int. Ed., 29, 1320, 1990 (b) P. J. Harrington, Transition Metals in Total Synthesis, Wiley, New York, 1990 Comprehensive Organic Synthesis, S. V. Ley (ed.), Pergamon Press, New York, 1991. 

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Carbene Reactions. The best procedure for preparing dihalocarbene adducts of olefins consists in stirring a haloform—methylene chloride solution with an excess of concentrated aqueous caustic soda in the presence of hen 2y1triethy1 amm onium chloride. Even stericahy hindered and electronically deactivated compounds give excellent yields (32). Mixed dihalocarbenes, CXY (X,Y = E, Cl, Br, I), except for CE2, can be prepared. 

Sodium difluoromethanesulfonate is prepared from chlorodifluoromethane and sodium sulfite The yield of this carbene reaction is more reproducible in the presence of sodium hydroxide [50] (equation 45)... 

The third volume of this series covers three specific groups of compounds the carbolines (reviewed by R. A. Abramovitch and I. D. Spenser), the thiatriazoles (K. A. Jensen and C. Pedersen), and the pentazoles (I. Ugi). The remaining four chapters deal with topics of general chemical interest from the heterocyclic viewpoint the quaternization of heterocyclics (G. F. Duffin), carbene reactions (C. W. Rees and C. E. Smithen), applications of the Hammett equation (H. H. Jaffe and H. Lloyd Jones), and some aspects of the nucleophilic substitution of heterocyclic azines (G. Rluminati). 

New catalysts and methods for enantioselective metal carbene reactions in syntheses of O- and N-heterocycles 98PAC1123. 

Metal Carbene Reactions from Dirhodium(ll) Catalysts... 

The mechanism through which catalytic metal carbene reactions occur is outlined in Scheme 2. With dirhodium(II) catalysts the open axial coordination site on each rhodium serves as the Lewis acid center that undergoes electrophilic addition to the diazo compound. Lewis bases that can occupy the axial coor-... 

The best known of metal carbene reactions, cydopropanation reactions, have been used since the earliest days of diazo chemistry for addition reactions to the carbon-carbon double bond. Electron-donating groups (EDG) on the carbon-carbon double bond facilitate this catalytic reaction [37], whereas electron-withdrawing groups (EWG) inhibit addition while facilitating noncatalytic dipolar cycloaddition of the diazo compound [39] (Scheme 5). There are several reviews that describe the earlier synthetic approaches [1, 2,4, 5,40-43], and these will not be duplicated here. Focus will be given in this review to control of stereoselectivity. 

Once formed by this process, the carbene may undergo any of the normal carbene reactions (see p. 250). When the net result is substitution, this mechanism has been called the SnIcB (for conjugate base) mechanism. Though the slow step is an SnI step, the reaction is second order first order in substrate and first order in base. 

Doyle MP (2004) Metal Carbene Reactions from Dirhodiimi(II) Catalysts. 13 203-222 Drudis-Sol6 G, Ujaque G, Maseras F, Lledos A (2005) Enantioselectivityin the Dihydroxyla-tion of Alkenes by Osmiimi Complexes. 12 79-107... 

TABLE 4.1. Estimated second-order rate constants for carbene reactions with CO2 in dichloromethane and IR frequencies of the corresponding a-lactones. ... 

Given the zwitterionic natnre of single carbenes, the possibility exists for coordinating solvents such as ethers or aromatic compounds to associate weakly with the empty p-orbital of the carbene. Several experimental stndies have revealed dramatic effects of dioxane or aromatic solvents on prodnct distribntions of carbene reactions. Computational evidence has also been reported for carbene-benzene complexes. Indeed, picosecond optical grating calorimetry stndies have indicated that singlet methylene and benzene form a weak complex with a dissociation energy of 8.7kcal/mol. ... 

Absolute rates have been measured for some carbene reactions. The rate of addition of phenylchlorocarbene shows a small dependence on alkene substituents, but as expected for a very reactive species, the range of reactivity is quite narrow.119 The rates are comparable to moderately fast bimolecular addition reactions of radicals (see Part A, Table 11.3). 

There are several reactions that are conceptually related to carbene reactions but do not involve carbene, or even carbenoid, intermediates. Usually, these are reactions in which the generation of a carbene is circumvented by a concerted rearrangement process. Important examples of this type are the thermal and photochemical reactions of a-diazo ketones. When a-diazo ketones are decomposed thermally or photochemically, they usually rearrange to ketenes, in a reaction known as the Wolff rearrangement.232... 

A sequence of reactions for conversion of acyclic and cyclic ketones into a,(3-unsaturated ketones with insertion of a =CHCH3 unit has been developed. The method uses l-lithio-l,l-dichloroethane as a key carbenoid reagent. The overall sequence involves three steps, one of them before and one after the carbenoid reaction. By analysis of the bonding changes and application of your knowledge of carbene reactions, devise a reaction sequence that would accomplish the transformation. 

Typical carbene reactions, such as norcaradiene formation with solvent (20) must be accepted, as must the occasional cyclopropanation of the trapping reagents. 

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