Reaction with diazoesters

Cu(OTf)2 generally gives yields intermediate between those of the other two catalysts, but with a closer resemblance to rhodium. In competition experiments, the better coordinating norbomene is preferred over styrene, just as in the case with Pd(OAc)2. Cu(acac)2, however, parallels Rh2(OAc)4 in its preference for styrene. These findings illustrate the variability of copper-promoted cyclopropanations, and it was suggested that in the Cu(OTf)2-catalyzed reactions of diazoesters, basic by-products, which are formed as the reaction proceeds, may gradually suppress... 

The q1-coordinated carbene complexes 421 (R = Ph)411 and 422412) are rather stable thermally. As metal-free product of thermal decomposition [421 (R = Ph) 110 °C, 422 PPh3, 105 °C], one finds the formal carbene dimer, tetraphenylethylene, in both cases. Carbene transfer from 422 onto 1,1-diphenylethylene does not occur, however. Among all isolated carbene complexes, 422 may be considered the only connecting link between stoichiometric diazoalkane reactions and catalytic decomposition [except for the somewhat different results with rhodium(III) porphyrins, see above] 422 is obtained from diazodiphenylmethane and [Rh(CO)2Cl]2, which is also known to be an efficient catalyst for cyclopropanation and S-ylide formation with diazoesters 66). 

Cu(II) EPR signal in nitriles as solvent as well as by polarographic measurements 144>. Similarly, the EPR signal disappeared when Cu(OTf)2 was used for catalytic cyclo-propanation of olefins with diazoesters 64). In these cases, no evidence for radical-chain reactions has been reported, however. The Cu(acac)2- or Cu(hfacac)2-eatalyzed decomposition of N2CHCOOEt, N2C(COOEt)2, MeCOC(N2)COOEt and N2CHCOCOOEt in the presence of cyclopropyl-substituted ethylenes did not furnish any products derived from a cyclopropylcarbinyl - butenyl rearrangement128. These results rule out the possible participation of electron-transfer processes and radical intermediates which would arise from interaction between the olefin and a radical species derived from the diazocarbonyl compound. 

The reactions of diazoesters with hydrochloric and sulfuric acids, triphenylphosphine, and dinitrogen tetroxide resulted in aryl chloroacetates, bis(aryloxycarbonylmethyl) sulfates, triphenylphosphoranylidenehydrazones of aryl 2-oxoethanoates, and iV-oxides of diaryl l,2,5-oxadiazole-3,4-dicarboxylates <1999RJO 666>. 

Mechanistic details of this reaction are scarce, but Aratani (14) mentions that the catalyst needs to be activated by heating in the presence of the diazo compound at 75-80°C until nitrogen evolution is observed and the color of the complex changes from green to brown. Reduction of the cupric precatalyst with a substituted hydrazine results in a yellow cuprous complex capable of inducing an instantaneous decomposition of diazoacetate at ambient temperature. Aratani proposes that the active catalyst is tetrahedral Cu(I), 26 in Scheme 2. Reaction with the diazoester from the less hindered face forms the Cu carbenoid having one hemilabile ligand (al-... 

Jacobsen, Panek and co-workers (86) investigated the intermolecular Si-H bond insertion of diazoesters. Bis(oxazolines) and diimines were found to be effective in this reaction, with diimine enf-88a providing optimal selectivities. As expected, enantioselectivity is a function of silane structure, with bulkier silanes providing higher selectivities but lower reactivity. Both CuOTf and Cu(OTf)2 catalyze this reaction but the Cu(II) precursors leads to much lower enantioselectivity (44% vs 83% at -40°C). 

The Z-alkene ( ) was subjected to the same sequence (Scheme 4). The triflate ( ) was easily obtained, but in this case reaction with azide ion gave directly the diazoester (22). Molecular models show that the triazoline corresponding to (19) has severe steric interactions and is more accessible to deprotonation (cf. ref. 23). 

In 1996, chiral intermediate Ru-Pybox-carbene complexes 23 and 24 were isolated by the reaction with Ru-Pybox-ethylene complex 8 and diazoesters having bulky ester groups, 2,6-di-ferf-butyltolyl or 1,3,5-trimethylphenyl for 24... 

Transition metal-catalyzed decomposition of a-diazoesters of type 60 result in the formation of a benzo[intramolecular Diels-Alder reaction with a tethered vinyl group followed by spontaneous N-assisted opening of the endoxide bridge to yield 11-azasteroid analogs (Scheme 92) <1999J(P1)59>. 

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. ... 

Other substituted diazoalkanes react differently. On reaction with HgCl2, such diazoesters as N2CHC02Et provide products that result from both insertion and mercuration of the acidic a hydrogen ... 

New evidence as to the nature of the intermediates in catalytic diazoalkane decomposition comes from a comparison of olefin cyclopropanation with the electrophilic metal carbene complex (CO)jW—CHPh on one hand and Rh COAc) / NjCHCOOEt or Rh2(OAc)4 /NjCHPh on the other . For the same set of monosubstituted alkenes, a linear log-log relationship between the relative reactivities for the stoichiometric reaction with (CO)5W=CHPh and the catalytic reaction with RhjfOAc) was found (reactivity difference of 2.2 10 in the former case and 14 in the latter). No such correlation holds for di- and trisubstituted olefins, which has been attributed to steric and/or electronic differences in olefin interaction with the reactive electrophile . A linear relationship was also found between the relative reactivities of (CO)jW=CHPh and Rh2(OAc) NjCHPh. These results lead to the conclusion that the intermediates in the Rh(II)-catalyzed reaction are very similar to stable electrophilic carbenes in terms of electron demand. As far as cisjtrans stereoselectivity of cyclopropanation is concerned, no obvious relationship between Rh2(OAc) /N2CHCOOEt and Rh2(OAc),/N2CHPh was found, but the log-log plot displays an excellent linear relationship between (CO)jW=CHPh and Rh2(OAc) / N2CHPh, including mono-, 1,1-di-, 1,2-di- and trisubstituted alkenes In the phenyl-carbene transfer reactions, cis- syn-) cyclopropanes are formed preferentially, whereas trans- anti-) cyclopropanes dominate when the diazoester is involved. 

By using Cu complexes of chiral spiro bis(oxazoline) ligand S, S,S)-23a as catalysts, the enantioselective catalytic insertion of a-diazoesters into N—H bond of aromatic amines was realized in high yields and high enantioselectivities (Scheme 43) [25b, 108]. The chiral spiro Cu catalysts have unique binuclear structures, as showing in Figure 6, which may address the excellent performance of the Cu-(S, S,S)-23a catalyst for this challenging reaction. With the Cu-catalyzed asymmetric N—H... 

Isoflavones result from a Suzuki coupling reaction with 3-iodochromones (Scheme 11) <05TL3707> and ring expansion of chromones by treatment with Me3SiOTf and a diazoester affords 2,3-benzoxepins via the benzopyrylium salt and cyclopropane derivative <05TL4057>. 

The direct transfer of carbene from diazocompounds to olefins catalyzed by transition metals is the most straightforward synthesis of cyclopropanes [3,4]. Reactions of diazoesters with olefins have been studied using complexes of several transition metals as catalysts. In most cases trans-isomers are preferably obtained, but the selectivity depends on the nature of the complex. In general the highest trans-selectivity is obtained with copper catalysts and it is reduced with palladium and rhodium complexes. Therefore, the rhodium mesotetraphenylporphyrin (RhTPPI) [5] and [(r 5-C5H5)Fe(CO)2(THF)]BF4 [6] are the only catalysts leading to a preference for the cis-isomer in the reaction of ethyl diazoacetate with styrene. 

Enantiocontrol in intramolecular cyclopropanation reactions of diazoacetamides has been developed to levels comparable with those now accessible with diazoesters. Several substituent variations in Eq. (20) are summarized in Table 3, which reveals examples where ee s exceed 90%. In general diazoamides have a conformational feature which differs from their diazoester counterparts, namely, the relatively slow syn-anti isomerization by rotation about the N-CO bond. If the interconversion of (18) and (19) or their respective metal carbenes is slow relative to the reaction timescale [50], only isomer (18) can lead to intramolecular cyclopropanation. However, an alternative process to which (18) is prone un-... 

Examples of enantioselective intramolecular C-H insertion reactions of diazoacetamides are known and though less extensive than those with diazoester substrates, there already are indications that excellent levels of stereocontrol are attainable. It is very likely that catalyst development will extend further the scope of this approach to the enantioselective synthesis of iY-heterocycles. 

These complexes also catalyze the enantioselective cyclopropanation of monosubstituted alkynes with bulky diazoesters [939, 1497] (Figure 7.87). Attempts at double diastereodifferentiation ( 1.6) have been carried out in the reaction of styrene with diazoesters of chiral alcohols under chiral Rh-3.61 complexes catalysis [939,1501], but disappointing selectivities were observed. 

There are few examples of the reactions of alkenes with diazoesters of chiral alcohols which give high face discrimination in rhodium-catalyzed reactions [936, 1497). However, Davies and coworkers [192, 193, 1503] have performed the reactions of alkenes with vinyldiazoesters of chiral alcohols under Rh2(OAc)4 or better yet Rh2(OCOC7H j 5)4 catalysis. The ester of (K)-pantolactone 1.16 is the most efficient substrate, and ftum-cyclopropanecarboxylates are obtained highly selectively. Starting from 7.141 (R = Ph), the enantioenriched plant hormone l-amino-2-phenylcyclopropanecarboxylic acid has been prepared (Figure 7.88). 

The reactions of diazoalkanes 9.21 with alkenes lead to pyrazolines 9.22, which are thermally transformed into cyclopropanes. Similar transformations occur during thermal reactions of diazoesters. The use of diazoesters of chiral alcohols did not give useful results, so chiral residues have been introduced on the olefin dipolarophile. Meyers and coworkers [327] carried out the reaction of diazomethane 9.21 (R = R = H) and diazopropane 9.21 (R = R = Me) with chiral lactams 1.92 (R = i-Pr or ferf-Bu, R = Me). These 1,3-dipolar cycloadditions are regioselective, but only CH2N2 leads to an interesting stereoselectivity (Figure 9.9). Morever, when the RM substituent of lactam 1.92 is H, the reaction is no longer stereoselective. 

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