1.3- Dienes copper catalysts

The use of chiral bis(oxazoline) copper catalysts has also been often reported as an efficient and economic way to perform asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines with conjugated dienes [81], with the main focus on the application of this methodology towards the preparation of biologically valuable synthons [82]. Only some representative examples are listed below. For example, the copper complex 54 (Scheme 26) has been successfully involved in the catalytic hetero Diels-Alder reaction of a substituted cyclohexadiene with ethyl glyoxylate [83], a key step in the total synthesis of (i )-dihydroactinidiolide (Scheme 30). 

Furans and some of its derivatives have been cyclopropanated with the ketocarbenoids derived from ethyl diazoacetate and copper catalysts. The 2-oxabicyclo[3.1.0]hex-3-enes thus formed are easily ring-opened to 1,4-diacylbutadienes thermally, thermo-catalytically or by proton catalysis 14,136). The method has been put to good use by Rh2(OAc)4-catalyzed cyclopropanation of furan with diazoketones 275 to bicyclic products 276. Even at room temperature, they undergo electrocyclic ring-opening and cis, trans-dienes 277a are obtained with fair selectivity 257,258). These compounds served as starting materials in the total syntheses 257 259) of some HETE s (mono-... 

In order to rationalize the catalyst-dependent selectivity of cyclopropanation reaction with respect to the alkene, the ability of a transition metal for olefin coordination has been considered to be a key factor (see Sect. 2.2.1 and 2.2.2). It was proposed that palladium and certain copper catalysts promote cyclopropanation through intramolecular carbene transfer from a metal carbene to an alkene molecule coordinated to the same metal atom25,64. The preferential cyclopropanation of terminal olefins and the less hindered double bond in dienes spoke in favor of metal-olefin coordination. Furthermore, stable and metastable metal-carbene-olefin complexes are known, some of which undergo intramolecular cyclopropane formation, e.g. 426 - 427 415). 

Asymmetric Diels-Alder reactions have also been achieved in the presence of poly(ethylene glycol)-supported chiral imidazohdin-4-one [113] and copper-loaded silica-grafted bis(oxazolines) [114]. Polymer-bound, camphor-based polysiloxane-fixed metal 1,3-diketonates (chirasil-metals) (37) have proven to catalyze the hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene. Best catalysts were obtained when oxovanadium(lV) and europium(III) where employed as coordinating metals. Despite excellent chemical yields the resulting pyran-4-ones were reported to be formed with only moderate stereoselectivity (Scheme 4.22). The polymeric catalysts are soluble in hexane and could be precipitated by addition of methanol. Interestingly, the polymeric oxovanadium(III)-catalysts invoke opposite enantioselectivities compared with their monomeric counterparts [115]. 

Intermolecular cyclopropanation of 2-substituted terminal diene 121 with rhodium or copper catalysts occurs preferentially at the more electron-rich double bond (equation 109)37162. With a palladium catalyst, considerable differences in regiocontrol can occur, depending on the substituent of the diene. In general, palladium catalysed cyclopropanation occurs preferentially at the less substituted double bond (equation 110). However, with a stronger electron-donating substituent present in the diene, e.g. as in 2-methoxy-l, 3-butadiene, the catalytic process results in exclusive cyclopropanation at the unsubstituted double bond (equation 110)162. 

A few examples are available in which regiocontrol in the cyclopropanation of non-conjugated diene is catalyst-dependent. An early example is showed in equation 118. Copper(II) triflate catalysed cyclopropanation of diene 132 with diazomethane occurs preferentially at the less substituted double bond, whereas copper(II) acetylacetonate in contrast promotes cyclopropanation at the more substituted double bond (equation 118)13. Regiocontrol in the cyclopropanation of norbornene derivative 133 is strongly catalyst-dependent (equation 119). When diphenyldiazomethane is used as carbenoid precursor, the regioselectivity of this cyclopropanation is significantly enhanced165. 

This nitrene-addition approach was used by Knight to synthesize vinyl aziridines from 1,3-dienes using PhI=NTs and a copper catalyst. The more electron-rich double bond is selectively transformed in most cases. When the electronic difference is negligible the regioselectivity is then determined by steric hindrance. A mixture of cis and tram isomers is usually obtained [95SL949],... 

More recently, Pfaltz has reported high enantioselectivities for the cyclopropanation of monosubstituted alkenes and dienes with diazo carbonyl compounds using chiral (semicorrinato)copper complexes (P-Cu) (23-25), and Evans, Masamune, and Pfaltz subsequently discovered exceptional enantioselectivities in intermolecular cyclopropanation reactions with the analogous bis-oxazoline copper complexes (26-28). With the exception of the chiral (camphorquinone dioximato)cobalt(II) catalysts (N-Co) reported by Nakamura and coworkers (29,30), whose reactivities and selectivities differ considerably from copper catalysts, chiral complexes of metals other than copper have not exhibited similar promise for high optical yields in cyclopropanation reactions (37). 

For the aziridination of 1,3-dienes, copper catalysis gave better yields of A-tosyl-2-alkenyl aziridines with 1,3-cyclooctadiene, 1,4-addition occurred exclusively (50%) [46]. Good results were also obtained on rhodium catalysed decomposition of PhI=NNs (Ns = p-nitrophenylsulphonyl) with some alkenes the aziridination was stereospecific, whereas with chiral catalysts asymmetric induction (up to 73% ee) was achieved. However, cyclohexene gave predominantly (70%) a product derived from nitrene insertion into an allylic carbon-hydrogen bond [47]. 

Cyclopropanation. Rhodium(II) pivalate is superior to copper catalysts for the cyclopropanation of l,l-dihalo-4-methylpenta-l,3-dienes (1) with ethyl diazoacetate. The yield is higher than that obtained with copper catalysts (48%), and the cis/trans ratio is considerably higher. Similar contrathermodynamic product ratios were observed with other substrates. 

Cyclic and acyclic enol derivatives 480 can be asymmetrically aziridinated with (A -tosylimino)iodobenzene 481 using a chiral copper catalyst prepared in situ from [Cu(MeCN)4]PF6 and the optically active ligand 479. Collapse of the aminal (i.e., 482) leads to the formation of enantiomerically enriched Q-amino carbonyl compounds 483, although ee s to date are modest <2000EJ0557>. Similarly, dienes can be selectively aziridinated using the chiral Mn-salen complex 484 to give vinyl aziridines 486 in scalemic form (Scheme 124) <2000TL7089>. 

Similarly, ra 5-cyclopropanes were obtained from alkenes, such as styrene and 2,5-dimethyl-hexa-2,4-diene, with relative yields > 90% when a diazoacetate bearing a bulky ester group was decomposed by a copper catalyst with bulky salicylaldimato ligands. Several metal complexes with bulky Cj-symmetrlc chiral chelating ligands are also suitable for this purpose, e.g. (metal/ligand type) copper/bis(4,5-dihydro-l,3-oxazol-2-yl)methane copper/ethyl-enediamine ruthenium(II)/l,6-bis(4,5-dihydro-l, 3-oxazol-2-yl)pyridine cobalt(III)/ salen. The same catalysts are also suited for enantioselective reactions vide infra). For the anti selectivity obtained with an osmium-porphyrin complex, see Section 1.2.1.2.4.2.6.3.1. 

Cp2TiCl2-catalyzed hydromagnesation of alkynes, alkenes, and conjugated dienes has been described in Section 3.2, in which the method of preparation of organomagnesium compounds was discussed. Here, carbomagnesation of acetylenic bonds in the presence or absence of a copper catalyst will be discussed. 

Although a variety of transition metal salts are effective, copper salts have been most extensively investigated. Unfortunately, polymerization of 1,3-dienes has not been successful by ATRP due to chelation of the copper catalyst by isoprene (Wootthikanokkhan et al., 2001). 

Butadiene is chlorinated in the gas phase to give mixtures of 1,2-dichlorobut-3-ene and l,4-dichlorobut-2-ene, which are interconvertible in the presence of copper catalysts. The former is dehydrochlorinated by contact with aqueous sodium hydroxide, to give chloroprene (2-chlorobuta-l, 3-diene) for polymer production (neoprene). The earlier acetylene-dimer route has been phased out. U.S. production of neoprene has fallen to about 120 kt per annum, of which over 40% is exported European production is somewhat lower. 

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