Cyclopropane, diazo decomposition with

Electron-withdrawing substituents generally increase diazo compounds stability toward decomposition. Dicarbonyl diazomethane, which bears two carbonyl groups flanking the diazomethane carbon, are more stable than diazo compounds with only one carbonyl substituent. In general, metal catalysed decomposition of dicarbonyl diazomethane requires higher temperature than does monocarbonyl substituted diazomethane. As indicated before, rhodium(II) carboxylates are the most active catalysts for diazo decomposition. With dicarbonyl diazomethane, the rhodium(II) carboxylate-promoted cyclopropanation process can also be carried out under ambient conditions to afford a high yield of products. 

Although dirhodium(II) carboxamidates are less reactive toward diazo decomposition than are dirhodium carboxylates, and this has limited their uses with diazomalonates and phenyldiazoacetates, the azetidinone-ligated catalysts 11 cause rapid diazo decomposition, and this methodology has been used for the synthesis of the cyclopropane-NMDA receptor antagonist milnacipran (17) and its analogs (Eq. 2) [10,58]. In the case of R=Me the turnover number with Rh2(45-MEAZ)4 was 10,000 with a stereochemical outcome of 95% ee. 

The starting diazo esters 110 were prepared by diazo transfer from the corresponding malonate esters 109. A selection of chiral Hgands in conjunction with 2mol% (with respect to the diazo compound) of [Cu(OTf)2] in (CH2C1)2 was then examined at 65 °C (Scheme 31). All of the Hgands tested were sufficiently reactive to produce diazo decomposition at 65 °C, although the yields of cyclopropanation products were quite variable. Even tertiary... 

Certain transition metal complexes catalyze the decomposition of diazo compounds. The metal-bonded carbene intermediates behave differently from the free species generated via photolysis or thermolysis of the corresponding carbene precursor. The first catalytic asymmetric cyclopropanation reaction was reported in 1966 when Nozaki et al.93 showed that the cyclopropane compound trans- 182 was obtained as the major product from the cyclopropanation of styrene with diazoacetate with an ee value of 6% (Scheme 5-56). This reaction was effected by a copper(II) complex 181 that bears a salicyladimine ligand. 

A variation on the thermal reactions of diazo compounds with alkenes is the decomposition of salts of sulfonylhydrazones. This procedure, known as the BamfoTd-Stevens reaction, is believed to occur via the formation of diazo compounds. Subsequent 1,2-hydrogen shifts generally lead to the formation of alkenes as the final products. Cyclopropanes may also be formed as the result of intramolecular 1,3-C—H insertion reactions or when the original hydrazone substrate contains a remote alkenic group as a site for intramolecular cyclopropanation.10... 

Tosylhydrazones of aliphatic aldehydes and ketones react with a base in an aprotic solvent at 90-180 C to give diazo compounds which undergo thermal decomposition with loss of nitrogen to yield alkenes derived from hydrogen migration and cyclopropanes from intramolecular insertion. In proton donor solvents decomposition of y-tosylhydrazones by base occurs primarily by a cationic mechanism involving diazonium and/or carbenium ion intermediates. 

With P-keto-a-diazoester 114 in hand, treatment with copper triflate in dichloromethane set up an elegant cascade reaction to construct pyrroloindole 117. This transformation is proposed to proceed via initial diazo decomposition and cyclopropanation of the indole ring to provide indoline... 

Binuclear Rhodium(ll) Catalysts. Soon after the first report of dirhodium(ll) carboxylates 1 (Scheme 1) as effective catalysts for diazo decomposition in 1973 (21), this type of complex was discovered to actively catalyze cyclopropanation (22). Comparison of relative reactivity and stereoselectivity of catalyst 1 (R = CHs) and a stoichiometric carbene complex of (COsWCHPh for cyclopropanation of alkenes with phenyldiazomethane showed rhodium carbene involvement in the rhodium-catalyzed cyclopropanation (23). Catalyst 1 (R = CH3) also demonstrated improvement of cyclopropane production can be achieved by decreasing the available concentration of the diazo compound with a slow addition method (24). 

Diazo Compounds Decomposition with Chiral Copper Catalysts. One of the important developments in copper-catalyzed cyclopropanation concerns the asymmetric version of the reaction. Although enantioselectivity was low... 

Diazo Compounds Decomposition with Chiral Rhodium Catalysts. The first chiral rhodium catalyzed asymmetric cyclopropanation was reported in 1989 (75). Structures of the catalysts were based on the framework of dirhodium(II) tetrakis(carboxylate) 1 with the carboxylate ligands replaced with... 

Occasionally, systems with complexes of ruthenium and cobalt have been reported to catalyze intramolecular cyclopropanation of allylic diazoacetate with high enantiocontrols. For cobalt-salen 39, up to 97% ee was observed (Scheme 30) (128). More recently, methods other than diazo decomposition were applied in intramolecular cyclopropanation. Activated by irradiation, [WlCOle] catalyzed the cyclopropanation of alkynol to give good yield of cyclopropane (Scheme 31) (129). The reaction was proposed via a tungsten—carbene intermediate. 

Diazo compounds are commonly used as a carbene source in organic chemistry. A few systems based on metals such as Ru and Rh have been reported for the transfer of carbenes from diazo compounds. P6rez and coworkers reported NHC-copper systems for carbene and nitrene transfer. In the first report, [Cu (Cl)(IPr)] was used for the transfer to olefins, amines, and alcohob [64]. The main transformation was the cyclopropanation of styrene with ethyl diazoacetate (Scheme 8.24). Monitoring of the reaction showed a fast formation of the product (90% conversion in 6 h). The absence of styrene does not lead to the decomposition of EDA even after a long period of time (13 h). Decent stereoselectivity was obtained with styrene (cisitrans 32/68) and cyclooctene exolendo 73/27). 

As outlined in Scheme 13.25, when the diazo ketone 166 was treated with CuOTf, the diazo decomposition formed a carbene intermediate, which reacted with the double bond of the pyrrole ring to yield the cyclopropane 167. The cyclopropane ring... 

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),... 

Muller et al. have also examined the enantioselectivity and the stereochemical course of copper-catalyzed intramolecular CH insertions of phenyl-iodonium ylides [34]. The decomposition of diazo compounds in the presence of transition metals leads to typical reactions for metal-carbenoid intermediates, such as cyclopropanations, insertions into X - H bonds, and formation of ylides with heteroatoms that have available lone pairs. Since diazo compounds are potentially explosive, toxic, and carcinogenic, the number of industrial applications is limited. Phenyliodonium ylides are potential substitutes for diazo compounds in metal-carbenoid reactions. Their photochemical, thermal, and transition-metal-catalyzed decompositions exhibit some similarities to those of diazo compounds. 

Metal-Catalyzed. Cyclopropanation. Carbene addition reactions can be catalyzed by several transition metal complexes. Most of the synthetic work has been done using copper or rhodium complexes and we focus on these. The copper-catalyzed decomposition of diazo compounds is a useful reaction for formation of substituted cyclopropanes.188 The reaction has been carried out with several copper salts,189 and both Cu(I) and Cu(II) triflate are useful.190 Several Cu(II)salen complexes, such as the (V-f-butyl derivative, which is called Cu(TBS)2, have become popular catalysts.191... 

As it is known from experience that the metal carbenes operating in most catalyzed reactions of diazo compounds are electrophilic species, it comes as no surprise that only a few examples of efficient catalyzed cyclopropanation of electron-poor alkeiies exist. One of those examples is the copper-catalyzed cyclopropanation of methyl vinyl ketone with ethyl diazoacetate 140), contrasting with the 2-pyrazoline formation in the purely thermal reaction (for failures to obtain cyclopropanes by copper-catalyzed decomposition of diazoesters, see Table VIII in Ref. 6). 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

The catalytic activity of rhodium diacetate compounds in the decomposition of diazo compounds was discovered by Teyssie in 1973 [12] for a reaction of ethyl diazoacetate with water, alcohols, and weak acids to give the carbene inserted alcohol, ether, or ester product. This was soon followed by cyclopropanation. Rhodium(II) acetates form stable dimeric complexes containing four bridging carboxylates and a rhodium-rhodium bond (Figure 17.8). 

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