In carbene additions

In a very different area of organic chemistry Ken produced a series of landmark theoretical papers on carbene reactions. He developed a general theory, showing how orbital interactions influence reactivity and selectivity in carbene additions to alkenes. Ken also showed how entropy control of reactivity and negative activation barriers in carbene addition reactions could both be explained by a new, unified model. 

Among other polymer-bound catalysts, onium compounds can be used successfully in halogen exchange reactions between activated and nonactivated halides. This is the case, for instance, in additions to the double bonds of dichlorocarbene to form substituted cyclopropanes and in C-alkylating nitriles. When optically active polymeric ammonium compounds are used as catalysts in carbene addition reaction, chiral products form. ... 

Triphase catalysts were also used for C-alkylations (Komeili-Zadeh, 1978) and have been shown to promote asymmetric addition in carbene addition reactions (Chiellini and Solaro, 1977 Colonna et al., 1978). Ammonium groups have been replaced by phosphoric triamides (Tomoi et al., 1978), phosphonium groups (Tundo, 1978), and polyethylene glycol (Regen and Dulak, 1977) to provide alternate phase-transfer agents. 

Carbene addition reactions are expected to be very exothermic since two new a bonds are formed and only a tt bond is broken. The reactions are very rapid and, in fact, theoretical treatment of the reaction of methylene (-CH2) with ethylene suggests that there is no activation barrier." Thus the slow step in carbene addition reactions under most circumstances is generation of the carbene. 

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

Organometallic complexes of copper, silver, and gold are ideal precursors for carbene complexes along with some C- and N-coordinated species. Their reactivity pattern, in particular in oxidative addition reactions, was the most comprehensively studied. 

Photolytically generated carbene, as mentioned above, undergoes a variety of undiscriminated addition and insertion reactions and is therefore of limited synthetic utility. The discovery (3) of the generation of carbenes by the zinc-copper couple, however, makes carbene addition to double bonds synthetically useful. The iodo-methylzinc iodide complex is believed to function by electrophilic addition to the double bond in a three-center transition state giving essentially cis addition. Use of the... 

Seyferth (7) discovered that phenyl(trihalomethyl)mercury compounds decompose when heated in a solvent giving dihalocarbenes. When the solvent contains a suitable olefin, carbene addition occurs giving 1,1-dihalocyclopropane derivatives. The reaction has the advantage that strong base is not required in the reaction mixture, and base-... 

Dichlorocarbene, generated by the action of 50 % potassium hydroxide on chloroform, adds to ethyl 1 W-azepine-l-carboxylate to furnish the all /rntu-trishomoazepine 12 in 35% yield280 (see Houben-Weyl, Vol. E 19b, p 1523). Subsequently, and as a result of a careful and detailed study of the addition of dichlorocarbene generated by the thermal decomposition of phenyl(trichloromethyl)mercury, it was deduced that carbene addition takes place sequentially in the order C4 —C5, C2—C3 and C6 — Cl. The intermediary mono- 10 and bis(dichlorocar-bene) 11 adducts have been isolated and characterized. 

Chlorins are also accessible by carbene additions to C-C double bonds on the periphery of metalloporphyrins. The most effective reaction on a preparative scale is the addition of ethyl diazoacetate in refluxing benzene to copper octaethylporphyrin (4) or meso-tetraphenylpor-phyrin in the presence of copper(I) iodide,100108b 110 which gives a diastereomcric mixture of chlorins, e.g. 5. 

The 1,3-dipolar cycloadditions are a powerful kind of reaction for the preparation of functionalised five-membered heterocycles [42]. In the field of Fischer carbene complexes, the a,/ -unsaturated derivatives have been scarcely used in cyclo additions with 1,3-dipoles in contrast with other types of cyclo additions [43]. These complexes have low energy LUMOs, due to the electron-acceptor character of the pentacarbonyl metal fragment, and hence, they react with electron-rich dipoles with high energy HOMOs. 

Aziridines can be prepared directly from double-bond compounds by photolysis or thermolysis of a mixture of the substrate and an azide. The reaction has been carried out with R = aryl, cyano, EtOOC, and RSO2, as well as other groups. The reaction can take place by at least two pathways. In one, the azide is converted to a nitrene, which adds to the double bond in a manner analogous to that of carbene addition (15-62). Reaction of NsONHC02Et/ CuO [Ns = A(/7-toluenesulfonyl-inimo)] and a conjugated ketone, for example, leads to the A-carboethoxy aziridine derivative.Calcium oxide has also been used to generate the nitrene.Other specialized reagents have also been used." ... 

Perhaps the most characteristic property of the carbon-carbon double bond is its ability readily to undergo addition reactions with a wide range of reagent types. It will be useful to consider addition reactions in terms of several categories (a) electrophilic additions (b) nucleophilic additions (c) radical additions (d) carbene additions (e) Diels-Alder cycloadditions and (f) 1,3-dipolar additions. 

Chiral diamino carbene complexes of rhodium have been merely used in asymmetric hydrosilylations of prochiral ketones but also in asymmetric addition of aryl boron reagents to enones. 

Roland et al. obtained 23% ee in the addition of Et2Zn to cyclohexenone using the silver(I) complex 78 having a chiral backbone and methyl groups on the nitrogen atoms. This complex acts as an efficient carbene transfer agent towards Cu(OTf)2. The conjugate addition proceeds rapidly in toluene at 0 °C (Scheme 52). 

An important synthetic application of this reaction is in dehalogenation of dichloro- and dibromocyclopropanes. The dihalocyclopropanes are accessible via carbene addition reactions (see Section 10.2.3). Reductive dehalogenation can also be used to introduce deuterium at a specific site. The mechanism of the reaction involves electron transfer to form a radical anion, which then fragments with loss of a halide ion. The resulting radical is reduced to a carbanion by a second electron transfer and subsequently protonated. 

HOMO-LUMO interactions in carbene alkene addition... 

The key cyclization in Step B-2 was followed by a sequence of steps that effected a ring expansion via a carbene addition and cyclopropyl halide solvolysis. The products of Steps E and F are interesting in that the tricyclic structures are largely converted to tetracyclic derivatives by intramolecular aldol reactions. The extraneous bond was broken in Step G. First a diol was formed by NaBH4 reduction and this was converted via the lithium alkoxide to a monomesylate. The resulting (3-hydroxy mesylate is capable of a concerted fragmentation, which occurred on treatment with potassium f-butoxide. 

The effect of metal basicity on the mode of reactivity of the metal-carbon bond in carbene complexes toward electrophilic and nucleophilic reagents was emphasized in Section II above. Reactivity studies of alkylidene ligands in d8 and d6 Ru, Os, and Ir complexes reinforce the notion that electrophilic additions to electron-rich compounds and nucleophilic additions to electron-deficient compounds are the expected patterns. Notable exceptions include addition of CO and CNR to the osmium methylene complex 47. These latter reactions can be interpreted in terms of non-innocent participation of the nitrosyl ligand. 

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