Copper bis-oxazoline

In conclusion, many chiral pyridine-based ligands have been prepared from the chiral pool and have been successfully tested as ligands for the copper- or rhodium-catalyzed cyclopropanation of olefins. Alfhough efficient systems have been described, sometimes leading interestingly to the major cis isomer, the enantioselectivities usually remained lower than those obtained with the copper-bis(oxazoline) system. 

Clarke and Shannon also supported copper bis(oxazoline) complexes onto the surfaces of inorganic mesoporous materials, such as MCM-41 and MCM-48, through the covalent binding of the ligand, modified by alkoxysilane functionalities [59]. The immobilized catalysts allowed the cyclopropanation of styrene with ethyldiazoacetate to be performed as for the corresponding homogeneous case, and were reused once with almost no loss of activity or selectivity. 

Many examples of asymmetric reactions catalyzed by copper complexes with chiral ligand systems have been reported. In particular, various copper-bis(oxazoline) catalysts (e.g., complexes (H) to (L), Scheme 48) are effective for carbon-carbon bond-forming reactions such as aldol,204 Mukaiyama-Michael, Diels-Alder,206 hetero Diels-Alder,207,208 dipolar cycloaddition,209,210... 

With chiral catalysts, the reaction becomes enantioselective. Among the successful catalysts are diisopropoxyTi(IV) BINOL and copper bis-oxazoline complexes. 

A new thioester aldol reaction which uses a half-thioester (PhS0C- CHMe-C02H) of methylmalonic acid and a copper-bis(oxazoline) catalyst is highly enantio- and diastereo-selective, while also being mild and tolerant of protic functional groups and enolizable aldehydes.136... 

Finally, though not strictly a hydroamination reaction, the asymmetric addition of alkynes to imines with a copper-bis(oxazoline) complex is worth briefly mentioning.[144] The nature of the ionic liquid cation has a strong effect on the enantioselectivity of the reaction and it appears that a good balance between hydrophobicity and acidity play an important role with best results obtained with [C4Ciim][Tf2N]. 

Hetero-Diels-Alder Cycloaddition Reactions. Copper-bis-(oxazoline) complex (2) facilitates a variety of asymmetric hetero-Diels-Alder reactions between a diverse range of substrates. A... 

Catalytic enantioselective versions of the inverse electron demand cycloaddition have also been reported. For example, the C-(diisopropylamino)carbonyl A -phenyl nitrone reacted with 7-substituted allylic alcohols in the presence of diethylzinc, iodine, pyridine A -oxide, and a catalytic amount of enantiopure DIPT to afford 3,5-m-disubstituted isoxazolidines with high enantioselectivity (Scheme 124) <2002CL302>. Enantioselective cycloaddition of nitrones to enol ethers was achieved in the presence of chiral binaphthol-aluminium and chiral copper-bis(oxazoline) catalysts <1999JA3845, 1999CC811, 1999JOC2353, 2000JOC9080>. 

Ketone silyl enol ethers react with derivatives of diacyl azo compounds at room temperature245 or on heating242,243 (see also Eq. 82) as well as enantio-selectively under the influence of silver trifluoromethanesulfonate and BINAP (Eq. 93)244 or copper bis(oxazoline) complexes (Eq. 94). The latter is proposed to proceed via a formal hetero Diels-Alder adduct.252 Ketones themselves react with azodicarboxylic esters either thermally246,389,390 or in the presence of potassium carbonate390 but yields are low. Higher yields can be achieved with LDA,391 394 (see also Eq. 88), LiHMDS,395,396 or KOBu-r325 as the bases. Aryl diazonium... 

Silyl nitronates undergo enantioselective addition to aromatic aldehydes in the presence of an enantiomerically pure bifluoride derived from (7.103). In this approach the anti-adduct is the major diastereomer formed. Thus silyl nitronate (7.105) undergoes addition to benzaldehyde to give adduct (7.106) with high ee. Alternately the coupling of silyl nitronates can be achieved with high ee using Lewis acids such as copper bis-oxazoline catalyst (7.107) in combination with a fluoride... 

The observed sense of asymmetric induction is consistent with a square planar copper(II)-glyoxylate complex with approach of the ene from the face opposite to the nearby tert-butyl substituent. Copper bis-oxazoline catalysts have also been used in the intramolecular carbonyl ene reaction. For instance, unsaturated a-ketoester (7.200) undergoes ene cyclisation to give the product (7.201) with high ee in the presence of the catalyst derived from BOX-ligand (7.34) and Cu(OTf)2. ° ... 

The HDA reaction of activated ketones is also possible using copper bis-oxazoline complexes. The highest ees in this procedure have been obtained using the copper complex prepared from the bis(sulfoximine) (8.141), which possesses chiral sulfur atoms and provides up to 98% ee in the HDA reaction of 1,3-cyclohexadiene (8.138) with substrate (8.142). 

The magnesium and copper bis-oxazoline catalysts used in the asymmetric Diels-Alder reaction (see Section 8.1) display high levels of selectivity in the nitrone cyclo addition with bidentate, electron-deficient dipolarophiles. The magnesium bis-oxazoline catalysts effect moderate to good ee in the cycloaddition with oxazolidines such as (8.51), while copper bis-oxazoline complexes show good selectivity in the addition to bidentate pyrazolidinones rather than oxazo-lidinones and also a-hydroxyenones such as (8.75) used as substrates in the copper bis-oxazoline-catalysed Diels-Alder reaction. ... 

The copper-catalysed asymmetric cyclopropanation has been achieved using diazomethane gas, albeit with moderate yields and/or ee. Some of the best enan-tioselectivites (up to 75% ee) have been obtained by Charette and coworkers using copper bis-oxazoline ligands and cinnamate esters as substrates. 

Intramolecular cyclopropanation with copper bis-oxazoline catalysts have generally been less successful than with the Doyle rhodium catalyst (see Section 9.1.2). However, Shibasaki has shown that using bis-oxazoline ligand (9.16), good enantioselectivity is obtained in the cyclisation of the silyl enol ether (9.17). ° Bis-oxazolines such as (9.19) have also been used by Nakada and coworkers to effect cyclisation of a-diazo-(3-keto sulfones such as (9.20). The product (9.21) is obtained with good ee and is a useful polyfiinctional synthetic building block. 

In addition to amines and hydroxylamines, very high levels of enantioselection have been obtained during the conjugate addition of carbamates and hydrazoic acid using copper bis-oxazolines and aluminium(salen) complexes, respectively. ... 

Scheme 9.22 Chiral aziridination of styrene over a chiral copper bis-oxazoline complex supported in zeolite Y (from reference 59).

One approach to ent-4 -tetrahydrocannabinol, which is independent ofthe chiral pool, was developed by David Evans (reaction scheme see next page). [143] Via enantioselective Diels-Alder reaction on a copper-bis-(oxazoline) complex, there is obtained a cyclohexenecarboxamide, which after conversion into its benzyl ester and an exhaustive Grignard reaction gives ent-menth-l-ene-3,8-diol. Also this isomer can be converted in an analogous matmer stepwise into tetrahydrocannabinol. A -Tetrahydrocannabinol would be correspondingly accessible by use ofthe antipode ofthe catalyst. 

Metal bis(oxazoline) catalysts are also highly efficient at promoting asymmetric Diels-Alder reactions. Ishira developed a highly selective copper bis(oxazoline) catalyst for use in standard intermolecular Diels-Alder reactions. Arrayas and Carretero used a nickel bis(oxazoline) catalyst in inverse electron demand hetero Diels-Alder reactions of 1-azadienes for the production of functionalized piperidines. bis(oxazoline) catalysts in reactions pyrazolidinone dienophiles and determined that copper and palladium catalysts were most efficient. Sibi applied a copper bis(oxazoline) catalyst in a kinetic resolution experiment in which one enantiomer of dienophile 46 reacts selectively with cyclopentadiene to yield cycloadduct 48 and 98% ee... 

Asymmetric Aziridination of Alkenes. The copper-catalyzed aziridination reaction can be rendered enantioselective by the addition of chiral ligands. The first example of an enantioselective aziridination of an alkene employed the bis(oxazoline) ligand (4) (R = f-Bu) and copper(I) trifluoromethanesulfonate as the metal catalyst (eq 14). This catalyst system affords the aziridine in 97% yield and 61% ee. Other reports have appeared subsequently regarding the extended scope of this reaction. " Important contributions to this area include the copper/bis-(oxazoline)-catalyzed aziridination of aryl acrylate esters (eq 15) and the copper/bis(imine)-catalyzed aziridination of cyclic cis-alkenes with the bis(imine) ligand (5) (eqs 16 and 17). ... 

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