Cydopropanations diazo compounds

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),... 

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. 

Rhodium(II) acetate was found to be much more superior to copper catalysts in catalyzing reactions between thiophenes and diazoesters or diazoketones 246 K The outcome of the reaction depends on the particular diazo compound 246> With /-butyl diazoacetate, high-yield cydopropanation takes place, yielding 6-eco-substituted thiabicyclohexene 262. Dimethyl or diethyl diazomalonate, upon Rh2(OAc)4-catalysis at room temperature, furnish stable thiophenium bis(alkoxycarbonyl)methanides 263, but exclusively the corresponding carbene dimer upon heating. In contrast, only 2-thienylmalonate (36 %) and carbene dimer were obtained upon heating the reactants for 8 days in the presence of Cul P(OEt)3. The Rh(II)-promoted ylide formation... 

Dipolar cydoaddition of ethyl 2-(ethoxycarbonyl)-4,4-diphenyl-2,3-butadieno-ate 518 with CH2N2 or Ph2CN2 afforded bicyclic or monocyclic products 519 and 520, respectively. The possibility of extra cydopropanation depends on the steric effect of the diazo compound [234]. 

Dichlorocarbene is a typical singlet ground-state carbene which is commonly used for cydopropanation reactions, since it gives satisfactory yields in many cases, but in general, carbene synthesis implies a metal catalyst (usually copper) together with a diazo compound as the carbene precursor. In (he particular case of the O -H insertion reaction, sulfur dioxide has been reported as being an efficient catalyst for the insertion of carbalkoxycarbenes generated from diazoesters. 

Nair V, Radhakrishnan KV, Sheela KC (1999) Res Chem Intermed 25 877 Doyle MP, McKervey MA, Ye T (1998) Modern Catalytic Methods for Organic Syn-theis with Diazo Compounds From Cydopropanes to Ylides. Wiley-Interscience, New York... 

Cyclopropcmation reactions are challenging as they involve the formation of highly strained three-membered rings. Cydopropane rings can be synthesized from a diazo precursor in the presence of a metal catalyst under mild conditions (Scheme 9.1) [37]. Initially, commercially available ethyl diazoacetate was employed as the carbene source for cyclopropanation reactions, but subsequently, other diazo compounds were developed for various carbene-transfer reactions... 

Another chiral auxiliary-based approach was documented by Davies (Equation 5) [8, 34]. These studies involved diazo compounds that incorporate vinyl and C=0 substitution and revealed that these stable carbene precursors participate in a variety of useful transformations, including diastereoselective cydopropanations. Importantly, Davies found that the cydopropanations with 33, in contrast with those of their simpler diazoacetate counterparts, are highly diastereoselective. The reaction with styrene and chiral diazo compound 33 is representative treatment of styrene with 33 in the presence of a simple Rh catalyst resulted in the formation of product 34 with high asymmetric induction dr 98.5 1.5) and in 84% yield. In this example, the panto-lactone auxiliaiy is a convenient, readily available chiral alcohol. 

In the photochemistry of a-diazo carbonyl compounds, singlet carbenes undergo a Wolff rearrangement while triplet carbenes react with alkenes to afford cydopropanes. 

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