Diazoalkanes reaction with copper derivatives

Diastereoselective cyclopropanation progressed in the reaction with sugar-derived glycals 143 (Scheme 1.69) [113]. A new type of spiro cyclopropanes 144 were formed in a highly stereoselective manner. Optically active enamide 145 underwent stereo-controUed cyclopropanation, and amide cyclopropanes 146 were prepared in more than 95 5 selectivity (Scheme 1.70) [114]. Cyclopropanation of 8-oxabicy-clo[3.2. l]octane 147 with diazoalkanes smoothly occurred in the presence of a rhodium or copper catalyst, and exo,exo adduct 148 was isolated in a highly stereoselective manner (Scheme 1.71) [115]. 

Polymer-supported benzenesulfonyl azides have been developed as a safe diazotransfer reagent. ° These compounds, including CH2N2 and other diazoalkanes, react with metals or metal salts (copper, paUadium, and rhodium are most commonly used) to give the carbene complexes that add CRR to double bonds. Diazoketones and diazoesters with alkenes to give the cyclopropane derivative, usually with a transition-metal catalyst, such as a copper complex. The ruthenium catalyst reaction of diazoesters with an alkyne give a cyclopropene. An X-ray structure of an osmium catalyst intermediate has been determined. Electron-rich alkenes react faster than simple alkenes. ... 

Condensation with carbonyl compounds. Formation of epoxides from aldehydes by reaction with sulfonium ylides is subject to asymmetric induction. The latter species have been generated from 91, 92, and 93, and also those derived from monoterpenes, e.g., 94 " and 95.- Of course the ylides can be obtained in situ by deprotonation of sulfonium salts or copper-catalyzed decomposition of diazoalkanes (with the carbenoids trapped by the sulfides). 

The copper-catalyzed cyclopropanation of alkenes with diazoalkanes is a particularly important synthetic reaction (277). The reaction of styrene and ethyl diazoacetate catalyzed by bis[/V-(7 )- or (5)-a-phenyl-ethylsalicylaldiminato]Cu(II), reported in 1966, gives the cyclopropane adducts in less than 10% ee and was the first example of transition metal-catalyzed enantioselective reaction of prochiral compounds in homogeneous phase (Scheme 90) (272). Later systematic screening of the chiral Schiff base-Cu catalysts resulted in the innovative synthesis of a series of important cyclopropane derivatives such as chrysanthemic acid, which was produced in greater than 90% ee (Scheme 90) (273). The catalyst precursor has a dimeric Cu(II) structure, but the actual catalyst is in the Cu(I) oxidation state (274). (S)-2,2-Dimethylcyclopropanecar-boxylic acid thus formed is now used for commercial synthesis of ci-lastatin, an excellent inhibitor of dehydropeptidase-I that increases the in vivo stability of the caibapenem antibiotic imipenem (Sumitomo Chemical Co. and Merck Sharp Dohme Co.). Attempted enantioselective cyclopropanation using 1,1-diphenylethylene and ethyl diazoacetate has met with limited success (211b). A related Schiff base ligand achieved the best result, 66% optical yield, in the reaction of 1,1-diphenylethylene and ethyl diazoacetate (275). 

The reaction system (6-37) includes the thermal azo-extrusion of a cyclic azo compound to a cyclopropane derivative and the direct formation of cyclopropanes, catalyzed by metal complexes. Synthetic routes to cyclopropane derivatives became an important subject in the last two decades, and one frequently used method is the 1,3-dipolar cycloaddition of a diazoalkane to an alkene followed by thermal or photolytic azo-extrusion of the 4,5-dihydro-3//-pyrazole formed to the cyclopropane derivative (6-37 A). This route can be followed in many cases without isolation, or even without direct observation, of the 4,5-dihydro-3//-pyrazole. Therefore, it is formally very similar to cyclopropane formation from alkenes with diazoalkanes, in which a carbene is first formed by azo-extrusion of the diazoalkane (see Sect. 8.3). As shown in pathway (6-37 B), this step can be catalyzed by copper, palladium, or rhodium complexes (see Sects. 8.2, 8.7, and 8.8). There are cases where it is not clearly known whether route A or B is followed. Scheme 6-37 also includes... 

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