CuOTf-catalyzed

The first highly enantioselective aziridination was reported in 1993 (76). Evans et al. found that cinnamate esters are excellent substrates for 55d CuOTf catalyzed... 

More complex ring systems have been built up using the CuOTf-catalyzed [2 + 2] photocydoaddition. For instance, transformation of the cydopentene derivative 21 leads in high yields to the tricyclic compounds 22a,b (Scheme 5.5, reaction 9) [27], with the endo isomer 22a being obtained in excess. The reaction was applied to... 

Due to its versatile applicability, the CuOTf-catalyzed [2 + 2] photocycloaddition was used successfully to study the topology of the intermolecular and intramolecular dimerization of norbomene derivates. When a racemic mixture of compound 27 is transformed in the presence of CuOTf, a 1 1 mixture of two stereoisomers (28a,b) is... 

Scheme 5.5 Intramolecular CuOTf-catalyzed [2 + 2] photocycloaddition, and its application to organic synthesis.

Copper(I) catalysis is very well established to promote intramolecular [2+2] photocycloaddition reactions of l,n-dienes (review [351]). The methodology recently enjoyed a number of applications [352-354], It is assumed that CuOTf, which is commonly applied as the catalyst, coordinates the diene and in this way mediates a preorganization. The Ghosh group recently reported a number of CuOTf-catalyzed photochemical [2+2] cycloaddition reactions, in which an organocopper radical complex was proposed as a cyclization intermediate (which should, however, have a formal Cu(II) oxidation state) (selected references [355-357]). A radical complex must, however, not be invoked, since the process may either proceed by a [2+2] photocycloaddition in the coordination sphere of copper without changing the oxidation state or according to a cycloisomerization/reductive elimination process. 

Photobicycliztttion of 6-dienes. Irradiation of the triene myrcene (1) affords three of the five possible [2 + 2] cycloadducts. Triplet-sensitized irradiation is more selective and results in the vinylcyclobutane 2 (75% yield) as the major product. Surprisingly, CuOTf-catalyzed photolysis results in the previously unknown vinylcyclobutane 3 (20% yield) in addition to the monocyclobutene 4 (35% yield). 

Cycloadditions. A chiral 2,2 -bipyridine (69) in which each nucleus is fused to a ferrocene has found use in a CuOTf-catalyzed asymmetric cyclopropanation. "" ... 

That CuOTf-catalyzed 2n + 2n photocycloadditions are not restricted to cyclic alkenes was first demonstrated in mixed cycloadditions involving allyl alcohol. To suppress homodimerization of e/jcto-dicyclopentadiene (i.e. eq 11) the diene to Cu ratio is maintained at < 1 1 and allyl alcohol is used as solvent. Under these conditions, a high yield of mixed cycloadduct is generated (eq 19). ... 

That both C=C bonds participating in 2n + 2n photocycloadditions can be acyclic is evident from the photobicyclization reactions of simple diallyl ethers that deliver bicyclic tetrahydrofurans (eq 20). In conjunction with ruthenium(IV) oxide-catalyzed oxidation by sodium periodate, these CuOTf-catalyzed photo-bicyclizations provide a synthetic route to butyrolactones from diallyl ethers (eq 20), The synthetic method is applicable to the construction of multicyclic tetrahydrofurans and butyrolactones from diallyl ethers (eq 21 and eq 22) as well as from homoallyl vinyl ethers (eq 23). ... 

Oxabicyclo[3.2.0]heptanes are also produced in the CuOTf-catalyzed photocycloadditions of allyl 2,4-hexadienyl ethers (eq 24). The CuOTf-catalyzed photocycloadditions of bis-2,4-hexadienyl ethers are more complex. Thus UV irradiation of 5,5 -oxybis[( )-l,3-pentadiene] in THF for 120 h produces vinylcy-clohexene and tricyclo[3.3.0.0 ]octane derivatives (eq 25). However, shorter irradiations reveal that these products arise by secondary CuOTf-catalyzed rearrangements of 6,7-divinyl-3-oxabicyclo[3.2.0]heptanes that are the primary photoproducts (eq 26). UV irradiation of the divinylcyclobutane intermediates in the presence of CuOTf promotes formal [1,3]- and [3,3]-sigmatropic rearrangements to produce a vinylcyclohexene and a 1,5-cyclooctadiene that is the immediate precursor of the tricyclo[3.3.0.0 ]octane. 

CuOTf-catalyzed photobicyclization of l,6-heptadien-3-ols produces bicyclo[3.2.0]heptan-2-ols (eq 27). In conjunction with pyrolytic fragmentation of the derived ketones, these CuOTf-catalyzed photobicyclizations provide a synthetic route to 2-cyclo-penten-l-ones from l,6-heptadien-3-ols (eq 28). The derived... 

An interesting application of copper-catalyzed aziridination is the preparation of ( )-olefin dipeptide isosteres based on a diastereoselective nitrene transfer onto chiral ( )-crotylsilanes (eq 86)7 CuOTf catalyzes the formation of an aziridine whose rearrangement after spontaneous desilylation affords allylamines. Excellent levels of acyclic stereocontrol can be achieved via a hydroxyl-assisted aziridination. Copper-catalyzed aziridination of enol ethers also leads to aziridines that undergo spontaneous rearrangement. Thus, CuOTf and particularly CUCIO4 mediate the formation of an a-methylserinal derivative from a 5-methyl-4//-1,3-dioxin (eq 87). ... 

Addition to Imines. CuOTf-catalyzed alkylation of N- acii-vated)imines also proceeds with dialkylzinc reagents. Use of a chiral amidophosphine leads to the asymmetric alkylation of N-(p-toluenesulfonyl)imines with dimethyl-, diethyl-, and di-E propylzinc in good yields and high enantioselectivities. CuOTf is the most active catalyst but efficiency is optimal with Cu(OTf)2 (eq 117). Chiral binaphthylthiophosphoramides give slightly lower selectivities. ... 

CuOTf-catalyzed C-S bond formation allows the formation of arylmethyl- and diarylsulfones. The coupling between aryl iodides and sulfinic acid salts proceeds in DMSO in the presence of A(A7-dimethylethylenediamine to give the sulfones with variable yields (eq 124). ... 

Structural variants of the chiral bis(oxazoline) ligands have been described for the CuOTf-catalyzed asymmetric JQiarasch reaction. Thus, a chiral CuOTf-tris(oxazoline) complex catalyzes the allylic oxidation of cyclopentene in 67% yield and with 66% ee. Cu(OTf)2 is, however, moderately more effective (68% yield, 74% ee). Ruorous bis(oxazolines), in which two... 

Asymmetric [2 + 2] Photocycloadditions. Intramolecular copper-catalyzed [2 + 2] photocycloaddition is a useful methodology for the preparation of bicyclic cyclobutanes and recent studies deal with its asymmetric version albeit with variable success. Diastereoselective reactions are achieved under the control of stereogenic centers incorporated in the dienic precursors. Both CuOTf and the more stable and easy to handle Cu(OTf)2 are suitable catalysts in this context. In the latter case, it is assumed that the copper(I) species is generated from Cu(OTf)2 under the photochemical conditions. A noteworthy example is the application of the CuOTf-catalyzed [2 + 2] photocycloaddition in the stereoselective total synthesis of the tricyclic sesquiterpene kel-soene (eq 128). ... 

The amine component was successfully replaced by carbamates 103 in the CuOTf-catalyzed synthesis of propargyl-carbamates 104 (Scheme 3.54), as reported by He, Li et al. Best results were obtained with -butyl carbamate and aromatic alkynes and aldehydes [144]. 

Benaglia and coworkers have developed a number of chiral ligands based on binaphthyl diamine (190) for CuOTf-catalyzed additions of terminal alkynes to preformed imines (Scheme 17.39) [51]. In a screen of the parent binaphthyl diamine (190) and N-alkylated derivatives, ligand (190) was found to provide moderate enantioselectivity in the addition of phenylacetylene (189) to imine (188). The selectivity could be improved by using bis-imine derivative (191) as the chiral ligand in the reaction [52]. 

A concise total synthesis of ( )-minfiensine was reported in 2008 by Qin with a 4% overall yield in 12 steps, which involved the highly efficient construction of functionalized tetracyclic carbazole framework through a cascade CuOTf-catalyzed cyclopropanation/ring opening/ring closure sequence (Scheme 13.25) [30]. 

Scheme 13.25 Total synthesis of ( )-minfiensine (170) using a cascade CuOTf-catalyzed cyclopropanation/ring opening/ring closure sequence.

CuOTf-catalyzed synthesis of polysubstituted pyrroles from a-diazoketones, nitroalkenes, and amines was reported by Lu, Wang, and coworkers. The corresponding polysubstituted pyrroles could be obtained in moderate yields using air as the oxidant. This cascade process of the polysubstituted pyrrole formation involves an NH insertion of carbene, a copper-catalyzed oxidative dehydrogenation of amine, and a [3+2] cycloaddition of azomethine ylide [21] (Scheme 8.9). 

Scheme 8.9 CuOTf-catalyzed synthesis of polysubstituted pyrroles from diazoketones, nitroalkenes, and amines.

Scheme 1.8 CuOTf-Catalyzed CDC reaction of diphenylmethane derivatives and aromatic all nes.

Trifluoromethylation reactions by cross-coupling in the presence of NHC-Cu species have also been reported. Although most of these methods remain stoichiometric in copper with the use of a pre-formed or in situ generated [(NHC)CuCF3] species, they represent a real breakthrough in the field of trifluoromethylation chemistry. Recently, Lalic also described the [(IPr)CuOTf]-catalyzed fluorination of alkyl triflates using KF as a fluoride source. This method is an elegant way to efficiently incorporate a fluorine atom on an aliphatic chain. It could be performed with radiolabeled F and therefore find some applications for PET probes. 

Polyfluorinated BOX ligand 228 provides a useful copper complex catalyst, which can be recovered easily from the reaction mixture by a fluorous solvent system [159]. Benaglia and coworkers reported that an F-BOX ligand with CuOTf catalyzed the asymmetric cyclopropanation of diazoacetate in a CgFig/CHaCN biphasic mixture the F-BOX ligand was readily separated from products by phase separation and recovered from the reaction mixture (Scheme 1.105). 

Stereoselective copper(l)-catalyzed [2 -I- 2]-photocycloaddition of 1,6-heptadienols has been used as a key step in the synthesis of several natural products. The total synthesis of the sesquiterpenes a-panasinsene 47 and P-panasinsene 48 has been achieved by CuOTf catalyzed photocycloaddition of the dienol 43 as the key step (Scheme 15). The resulting bicyclo[3.2.0]heptanol 44 was then converted to the natural products through the ketone 46. It is noteworthy that direct access to the requisite intermediate 46 involving photoaddition of isobutylene to the enone 45 failed, illustrating the importance of the copper(l)-catalyzed photocycloaddition of 1,6-heptadienols. 

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