Copper-mediated cyclopropanation

Copper-Mediated Cyclopropanation of Alkenes with Diethyl Dihromomaionate General Procedure ... 

The zinc homoenolates from cyclopropanes 15. react in the presence of MejSiCl/HMPA with a,[3-unsaturated ketones to give good yields of 1,6-D systems, by a copper-mediated (CuBr-Me2S) Michael-type addition (Table 5.4). 

Likewise, PEG-supported bisoxazoline (40) can be used as a ligand for copper-mediated enantioselective reactions such as cyclopropanations of alkenes, [2-1-4] cycloadditions as well as ene reactions. Best results were obtained in case of the latter reactions as products were formed in yields up to 96% and ee s up to 95% (Scheme 4.25) [117]. 

A copper-containing oxocarbenoid is assumed to be involved in the formation of both the cyclopropanes 9 and the 4,5-dihydrofurans 10. It is therefore not surprising that the formal cyclotrimers of oxocarbenes, triacylcyclopropanes 12, were obtained in the absence of suitable reagents that could trap the oxocarbenoid. Cyclopropanes 12 are likely to be formed via the formal oxocarbene dimers 11, which in some cases are also found among the reaction products. In addition to the copper-mediated debromination of a,a-dibromo ketones, triacylcyclopropanes can also be obtained from a,a-dihalo ketones by metal-induced a-elimination in other cases, e.g. from a,a-dibromo ketones with Ni(0), Fe(0), or Co(0) complexes,", and from a,a-dichloro ketones with a zinc-copper couple. 

A copper complex containing bis(trans-2,3-diphenylaziridin-l -yl)ethane as the chiral ligand mediated cyclopropanation of 1,1-diphenylethene with ethyl diazoacetate with an ee-value of 63% (yield 74%). 20[Pg.460]

The copper-, rhodium-, or ruthenium-mediated cyclopropanation of electron-deficient alkenes, such as a,[S-unsaturated carbonyl compounds, acrylonitriles or vinylboronates, fails in most cases and is very inefficient in others. One of the exceptions is the copper-catalyzed cyclopropanation of but-l-en-3-one with ethyl diazoacetate. ... 

The [Cu(Bp)] system has been employed to investigate kinetics of the ethyl diazoacetate decomposition reaction in the presence or absence of olefin. The available data have allowed the proposition for a copper-mediated olefin cyclopropanation reaction. It has been proposed that the real catalyst is a 14-electron species, independent of the nature of the ligand bonded to the copper center.50... 

Azabicyclo[3.1.0] hex-2-enes and 4-carbonylpyrroles could be obtained respectively via copper-mediated/catalyzed reactions of Af-allyl/propargyl enamine carboxylates under an O2 atmosphere with different copper catalysts. Intramolecular cyclopropanation and carbooxygenation were involved during this reaction (Scheme 8.4). Three C(sp )-H bonds and one C(sp )-H bond were active for this transformation [14]. 

Evans et al. (34) reported preliminary results showing that 55c CuOTf is moderately selective in mediating the aziridination of styrene, producing the heterocycle in 61% ee. Lowenthal and Masamune (44) mention in a footnote to their cyclopropanation paper that the copper complex of camphor-derived bis(oxa-zoline) (103) provides the aziridine of styrene in 91% yield and 88% ee. However, this reaction has been found to be irreproducible (76,77) and further reports of aziridination from the Masamune laboratories have not appeared. 

As demonstrated below, a Lewis acid-mediated reaction was utilized in the synthesis of dihydro[b furan-based chromen-2-one derivatives from l-cyclopropyl-2-arylethanones and allenic esters <070L4017>. The TiCh-catalyzed anti-Markovnikov hydration of alkynes, followed by a copper-catalyzed O-arylation was applied to the synthesis of 2-substituted benzo[6]furan <07JOC6149>. In addition, benzo[6]furan-based heterocycles could be made from chloromethylcoumarins <07SL1951>, substituted cyclopropanes <07AGE1726>, as well as benzyne and styrene oxide <07SL1308>. On the other hand, DBU-mediated dehydroiodination of 2-iodomethyl-2,3-dihydrobenzo[6]furans was also useful in the synthesis of 2-methylbenzo[Z>]furans <07TL6628>. 

The control of carbene reactions from diazo compounds as precursors is classically mediated by copper catalysts and all the carbene reactions discussed in Section 8 are, in fact, improved by such catalysts. Moreover, the use of ligands on the metal allows some control of the stereochemistry of the products, the most striking example being the asymmetric synthesis of cyclopropanes with an excellent optical yield (>90S ce) [35]. 

This review details the utility of copper compounds in a variety of organic transformations wherein their principal function is as a Lewis acid. Other important organic transformations such as conjugate additions, cyclopropanations, oxidations, and aziri-dinations are also mediated by copper species. Copper does not, however, function as a Lewis acid in these reactions but acts as a reagent and these reactions are not discussed here. The chemistry described in this review highlights the role of copper in facilitating synthetic transformations and the readers should consult the primary literature for experimental details. 

An a-diazo ketone or ester such as (146) can also, via metal-mediated nitrogen loss, undergo 1,5 C— H insertion, to make the corresponding cyclopentane (147 equation 59). This process, most efficiently catalyzed by Rh dimers, is also reviewed in detail elsewhere in these volumes. It is striking that with copper bronze catalyst, (146) gives only intramolecular cyclopropanation. ... 

Cyclopropanation with zinc-copper couple and diiodomethane is still the method of choice for preparing precursor cyclopropyl compounds for further studies, as in the case of mercury(II)-mediated cyclization of (hydroperoxyalkyl)cyclopropanes." ... 

A novel soluble complex, (t/ -ethene)hydrotris(3,5-dimethylpyrazol-l-yl)boratocopper(I) (3) mediates the cyclopropanation of styrene, hex-1 -ene, and cyclooctene with ethyl diazoacetate in 76 96% yield (25 C, 1 mol% of catalyst).Copper complexes with the tridentate 2,6-bis[(5-oxo-2,5-dihydropyrrol-2-ylidene)methyl]pyridine ligand or homologous tetradentate l,T-bipyridine and l,T-biisoquinoline ligands are also suited to cyclopropanation of styrene with ethyl diazoacetate. 

In a related reaction, ethyl cyanoacetate is the source of the cyano(ethoxycarbonyl)methylene unit which is transferred to alkenes by a radical mechanism, e.g. synthesis of 3. This transformation is mediated by copper(II) chloride or acetate, accompanied by lithium chloride. Synthesis of diethyl cyclopropane-1,1-dicarboxylates from diethyl malonate and alkenes is much less efficient. ... 

The copper salt mediated synthesis of 1-alkoxycarbonylcyclopropane-l-carbonitriles from cy-anoacetates and alkenes or l,l-dichloro-4-methylpenta-1,3-diene is described in Section 1.2.1.2.4.2.9. An analogous synthesis of cyclopropane-1,1-dicarbonitriles has been claimed. Instead of l,l-dichloro-4-methylpenta-l,3-diene, 3,4-dibromo-l,l-dichloro-4-methylpent-l-ene can be utilized to form 1 (no yield given). ... 

Cyclopropanated allylboration reagents have been used to homoallylate and homocrotylate aldehydes. A zinc-mediated a-prenylation of aldehydes and ketones has been reported conventional conditions have yielded mainly the y-adduct to date. " A racemic allene has been hydroborated in an enantioconvergent manner the enantioenriched crotylborane then reacts with aldehydes in high ee to give ( j-stannyl-homoallylic alcohols. A copper-catalysed y-selective and stereospecific allylic alkylation of ketene silyl acetals has been reported. ... 

In a comparative study encompassing NHC complexes of all three coinage metals, Perez and Echavarren reported that [(IPr)AgCl] and [(SIPr)AgCl] were able to mediate the cyclopropanation reaction between styrene and phe-nyldiazoacetate, albeit in lower yield than their copper and gold analogues. ... 

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