Copper-carbenoid

The aza-[2,3]-Wittig rearrangement of a vinylaziridine-derived quaternary azir-idinium ylide (i.e., [2,3]-Stevens rearrangement) has recently been reported (Scheme 2.53) [86], The aziridinium ylide 219, generated by the intramolecular reaction of a copper carbenoid tethered to a vinylaziridine, underwent a [2,3]-Ste-vens rearrangement to furnish the bicydic amine 220 with the indolizidine skeleton. 

For the copper-induced decomposition of diazodiphenylmethane in acetonitrile, a fundamental difference in the catalytic action of Cu C104 and Cu ClO was detected. Whilst with CuC104, intermediary copper carbenoids are believed to be responsible for the mainly formed benzophenone azine402, CufClO initiates a chain reaction, promoted by radical cations and yielding mainly tetraphenylethene... 

It is known that the oxidation potentials of diazodiphenylmethane and Cu(I) in acetonitrile are very similar. With CuBr2 however, no radical-chain reaction takes place. Contrary to the copper perchlorates, CuBr2 and CuBr initiate identical reaction pathways involving copper carbenoids. No definite answer to this discrepancy is available 402). 

B uilding on the original proposal by Yates, the mechanism of this reaction is believed to involve the formation of copper carbenoids as intermediates, Scheme 1. Beyond the fact that copper, its ligands, the carbenoid fragment, and alkene are involved in the stereochemistry-determining event, as evidenced by Noyori et al. (2) and later by Moser (11, 12), little definitive mechanistic information has been acquired for this process. The basics of the mechanism will be discussed in this section. In subsequent sections detailing enantioselective variants, specific factors that have added to the understanding of this reaction will be addressed as will the models used to rationalize the observed stereochemistry. 

The seminal report of an asymmetric homogeneous metal-catalyzed reaction described the copper-catalyzed group-transfer reaction from a diazoester to an alkene, Eq. 3 (2). This article provided experimental verification of the intervention of copper carbenoid olefin complexes in the catalytic decomposition of diazo com-... 

In accord with previous proposals, Pfaltz and co-workers (30) suggested that this reaction proceeds by initial formation of copper carbenoid 47 (Scheme 3). Pfaltz does not invoke a metallacyclobutane intermediate but rather suggests that nucleophilic attack of the alkene on 47 with concomitant pyramidalization at the reacting centers forms two possible transition states with stereoselectivities deter-... 

Evans suggests that the catalyst resting state in this reaction is a 55c Cu alkene complex 58, Scheme 4 (35). Variable temperature NMR studies indicate that the catalyst complexes one equivalent of styrene which, in the presence of excess alkene, undergoes ready alkene exchange at ambient temperature but forms only a mono alkene-copper complex at -53°C. Addition of diazoester fails to provide an observable complex. These workers invoke the metallacyclobutane intermediate 60 via a formal [2 + 2] cycloaddition from copper carbenoid alkene complex 59. Formation of 60 is the stereochemistry-determining event in this reaction. The square-planar S Cu(III) intermediate 60 then undergoes a reductive elimination forming the cyclopropane product and Complex 55c-Cu, which binds another alkene molecule. 

There are no mechanistic details known from intermediates of copper, like we have seen in the studies on metathesis, where both metal alkylidene complexes and metallacyclobutanes that are active catalysts have been isolated and characterised. The copper catalyst must fulfil two roles, first it must decompose the diazo compound in the carbene and dinitrogen and secondly it must transfer the carbene fragment to an alkene. Copper carbene species, if involved, must be rather unstable, but yet in view of the enantioselective effect of the ligands on copper, clearly the carbene fragment must be coordinated to copper. It is generally believed that the copper carbene complex is rather a copper carbenoid complex, as the highly reactive species has reactivities very similar to free carbenes. It has not the character of a metal-alkylidene complex that we have encountered on the left-hand-side of the periodic table in metathesis (Chapter 16). Carbene-copper species have been observed in situ (in a neutral copper species containing an iminophosphanamide as the anion), but they are still very rare [9],... 

The copper carbenoid intermediates are electrophilic, and the cyclopropanation occurs with retention of configuration of the olefinic substrates 221a). The methylene transfer to the carbon-carbon double bond... 

Aratani, T. (1985) Catalytic asymmetric synthesis of cyclopropanecarboxylic acids an application of chiral copper carbenoid reaction. Pure Appl. Chem., 57, 1839. 

A diastereoselective synthesis of tetrahydropyran-3-ones 1021 can be achieved via [2,3]-sigmatropic rearrangement of the ylides 1022, generated from the achiral diazoketone 1023 via formation of a copper carbenoid followed by an... 

Insecticides of the pyrethroid class, such as trans-chrysanthemic acid (190), have significant commercial value (see Chapter 31).241 An asymmetric synthesis of 190 has been achieved through the use of a chiral copper carbenoid reaction (Scheme 12.77).242 243 With ethyl diazoacetate, equal amounts of the cis- and trans-cyclopropanes were formed. However, when the size of the alkyl... 

Other reactions. /3-Lactams, such as 182, were prepared in moderate to good yields by [2,3]-rearrangement of ammonium ylides produced by the reaction of copper carbenoids tethered to allylic amines (Scheme 77) <2001J(P1)3312>. The catalyst of choice in the generation of carbenoid/ylide from a-diazoketone precursor is copper(n) acetylacetonate. 

Carbene metal complexes are the reactive species in these catalyzed processes and arc known as carbenoids . Copper carbenoids are the most widely used catalysts in the mediation of carbene reactions. During the last decade, however, the use of other metal salts has been particularly beneficial (e.g., Rh.Pd). 

Carbenoids present a full range of reactivities some are extremely reactive species (e.g., copper carbenoids have never been observed, even by spectroscopy) others arc very stable compounds. Such a dramatic stabilization, discovered by Fischer [13), occurs when some soft transition metals complexes (Mo, W, Pd) are associated with a very stabilized (soft) carbene (e.g., alkoxy or dialkoxy-carbenes, heterocyclic carbenes, etc.). 

Asymmetric copper catalysts arc less efficient. Low optica) yields were obtained with chiral phosphine liijpinds, and these experimems wctc significant in proving the formation of copper carbenoids rather than free carbenes in the copper catalyzed decomposition of diaio compounds. From a practical point of view, however, the optical yield was too low to be of much interest. The best results with copper catalysts were those obtained by Aratani [36] using complex (36). 

With particular cupper catalysts bearing very weak ligands, Kochi observed unusual selectivities during the first stages of competitive cydopropanation of Ntexene and tetrameihylclhyienc [37], Two different mechanisms were thus recognized lor the copper carbenoid cydopropanation reactions. 

The divergent behavior of this photochemical reaction is an illustration of those instances where a free carbene and a copper carbenoid show different... 

Alternatively, a structure much less demanding than V such as VII could also result by intramolecular monoalkylation of the copper carbenoid IV. This intermediate contains an electron deficient center two atoms removed from a carbonyl function. This is the combination required for acidic-type cleavages such as in /3-dicarbonyls and /3-keto esters. One would expect, therefore, the occurrence of the nucleophilic attack-bond fragmentation sequence represented in structure VIII to yield II. 

Both V and VII are highly unstable species, as is copper carbenoid IV. It is conceivable that both evolutionary alternatives follow downhill energy profiles. Whatever the particular mechanism, the transformation of I into II has been termed the vinylogous Wolff rearrangement, since it was taken as a homolog of the classical Wolff transposition. 

Reaction involving the formation of a sulfonium intermediate (80) followed by a sigmatropic rearrangement was formulated by Trost and Biddlecom (Scheme 8) and cyclization initiated by an allylic copper carbenoid (81) was proposed by Cohen and coworkers (Scheme 9). The common feature of all of these proposed mechanisms relies on the electrophilic addition of the donor to the acceptor prenyl pyrophosphate and is... 

Exchanged copper ions in Y zeolite are located near supercages (47). As it has been proposed that copper carbenoid intermediates are involved in the copper-catalyzed dimerization of aryldiazomethanes (43), organocopper intermediates may be formed in narrow supercages. The excellent cis/trans selectivity is accounted for by the increased stability differences between the two intermediates (13c, 13t) leading to cis- and rrans-1,2-diarylethylenes, respectively, as shown in Fig. 5. Efficient catalysis of zeolite-encapsulated copper ions was proved in reactions of ethyl diazoacetate as well (48, 49). 

While these rhodium and copper carbenoids are unstable, some transition metals such as tungsten and chromium form stable, isolable carbenoids, called metallocarbenes or Fischer carbenes. 

Attempts to apply Rh(II)-catalysis conditions similar to those in the synthesis of piperidones 164 (n = 1) to substrates 163 ( = 2, 3 R = Ph) with one or two additional methylene units in the linker met with little success [164 (n = 2 R = Ph) 35% yield, (/i = 3 R = Ph) 0% yield]. Intramolecular C —H insertion to give cyclopentanones appeared to be the major pathway in these cases. Use of Cu(acac)2-catalyzed decomposition of 163 (n = 2, 3 R = Ph) furnishes 164 ( = 2, 3 R = Ph) in 61 and 58% yield, suggesting a remarkably efficient and selective capture of the copper carbenoid by the amine to give a medium-size cyclic ylide in preference to other carbenoid pathways (94JOC6892). 

Tandem intramolecular ylide formation and [2,3]-sigmatropic rearrangement from copper carbenoids is a useful method for preparing seven- and eight-membered cyclic amines 68 (n = 3, R = Me = 4, R = C-C3H5). The rhodium(II) acetate-catalyzed reaction is less effective (94CC2701). 

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