Carbenoid enantioselective cyclopropanation

Carbenoid complexes with heterocyclic ligands as catalysts in enantioselective cyclopropanation of olefins 97S137. 

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. 

For a reaction as complex as catalytic enantioselective cyclopropanation with zinc carbenoids, there are many experimental variables that influence the rate, yield and selectivity of the process. From an empirical point of view, it is important to identify the optimal combination of variables that affords the best results. From a mechanistic point of view, a great deal of valuable information can be gleaned from the response of a complex reaction system to changes in, inter alia, stoichiometry, addition order, solvent, temperature etc. Each of these features provides some insight into how the reagents and substrates interact with the catalyst or even what is the true nature of the catalytic species. 

Use of a chiral diazo ester proved less rewarding in terms of enantioselective cyclopropanation. Only very low enantiomeric excesses were obtained when styrene was cyclopropanated with the carbenoid derived from diazoacetic esters 219 bearing a chiral ester residue 214). 

The enantioselective cyclopropanation leading to 1,2,3-snbstitnted cyclopropane derivatives proceeds with high diastereocontrol (equation 86) . It is quite interesting to observe that the same reaction, when run in the absence of the dioxaborolane ligand, led to lower diastereoselectivity. Other functionalized 1,1-diiodoaLkanes can be used as the zinc carbenoid precursor, but it should be noted that up to 2 equivalents of the reagent (4 equivalents of RCHI2) are needed in this process. This reaction has been applied in the synthesis of ambruticin. ... 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

V K. Singh, A. DattaGupta, G. Sekar, Catalytic Enantioselective Cyclopropanation of Olefins Using Carbenoid Chemistry, Synthesis 1997, 137—149. 

Optically active metal complexes have been recognized as excellent catalysts for the enantioselective cyclopropanation of carbenes with alkenes. Normally, diazo compounds react under metal catalysts in the dark to afford carbenoid complexes as key intermediates. Katsuki et al. have reported the ds-selective and enantioselective cyclopropanation of styrene with a-diazoacetate in the presence of optically active (R,R)-(NO + )(salen)ruthenium complex 80, supported under illumination (440 nm light or an incandescent bulb) [59]. The irradiation causes dissociation of the apical ligand ON + in 80, and thus avoids the splitting of nitrogen from the a-diazoacetate. 

Denmark et al. studied the effect of zinc iodide on the catalytic, enantioselective cyclopropanation of allylic alcohols with bis(iodomethyl)-zinc as the reagent and a bismethanesulfonamide as the catalyst 17]. They found significant rate enhancement and an increased enantiomeric excess of the product cyclopropane upon addition of 1 equivalent zinc iodide. Their studies and spectroscopic investigations showed that the Schlenk equilibrium appears to lie far on the left (IZnCHjI). Charette et al. used low temperature - C-NMR spectroscopy to differentiate several zinc-carbenoid species [18]. They also found evidence that in the presence of zinc iodide, bis(iodomethyl)zinc is rapidly converted to (io-domethyOzinc iodide. Solid-state structures of (halomethyl)zinc species have been described by Denmark for a bis(iodomethyl)zinc ether complex (6a) [19] and Charette for an (iodo-methyl)zinc iodide as a complex with 18-crown-6 (6b) [20] (Fig. 2). 

Despite the fact that zine carbenoids have been studied quite extensively, little work has been done to modify the nature of the R group of the zinc reagent RZnCH2X . A recent finding that phenoxide derivatives ArOZnCH2l are very reactive species for the cyclopropanation of unfunctionalized olefins constitutes a first and promising step toward the development of an enantioselective cyclopropanation method for unfunctionalized olefins [36 c]. 

Heterocycles as ligands in enantioselective cyclopropanation reactions with zinc carbenoids 02MI7. 

The carbenoid reaction between a-diazo ketones and simple alkenes or styrenes leads to acylcyclopropanes. (For the enantioselective cyclopropanation of styrene with 2-diazo-5,5-dimethylcyclohexane-l,3-dione, see Section 1.2.1.2.4.2.6.3.2.). With ketene acetals, 2,3-dihyd-rofurans are obtained. In contrast, l-acyl-2-oxycyclopropanes or 2-oxy-2,3-dihydrofurans can be formed in reactions with enol ethers and enol acetates the result depends strongly on the substitution pattern of both reaction partners.Whereas simple diazo ketones usually lead to cyclopropanes (Table 15), 3-diazo-2-oxopropanoates and 2-diazo-l,3-dicarbonyl compounds, such as 2-diazoacetoacetates, 3-diazopentane-2,4-dione, and 2-diazo-5,5-dimethylcy-clohexane-1,3-dione, yield 2,3-dihydrofurans and occasionally acyclic structural isomers thereof when reacted with these electron-rich oxy-substituted alkenes. 

Enantioselective Cyclopropanations with Carbenoids Generated from Diazoalkanes... 

Enantioselective [2+1] Cycloaddition Cyclopropanation with Zinc Carbenoids... 

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