Styrene, asymmetric cyclopropanations, copper

Chelucci et al. [41] synthesized further chiral terpyridines derived from (-)-yd-pinene, (-i-)-camphor, and (-l-)-2-carene and tested their ability to chelate copper or rhodium for the asymmetric cyclopropanation of styrene. The copper catalysts were poorly efficient and selective in this reaction. The corresponding rhodium complexes led to the best result (64% ee) with the ligand derived from (-l-)-2-carene (ligand 33 in Scheme 17). 

Certain transition metal complexes catalyze the decomposition of diazo compounds. The metal-bonded carbene intermediates behave differently from the free species generated via photolysis or thermolysis of the corresponding carbene precursor. The first catalytic asymmetric cyclopropanation reaction was reported in 1966 when Nozaki et al.93 showed that the cyclopropane compound trans- 182 was obtained as the major product from the cyclopropanation of styrene with diazoacetate with an ee value of 6% (Scheme 5-56). This reaction was effected by a copper(II) complex 181 that bears a salicyladimine ligand. 

One of the earliest examples of such catalysis was demonstrated in 1966 by the Japanese chemist Hitosi Nozaki, who reacted styrene and ethyl diazoacetate in the presence of a chiral Schiffbase-Cu11 complex [72-74], Although the initial enantios-electivity was modest (<10% ee), the principle was proven. Some years later, the companies Sumitomo and Merck used similar copper catalysts for asymmetric cyclopropanation on a multikilogram scale, in the production of various insecticides and antibiotics [75]. One of Nozaki s PhD students at that time was Rioji Noyori, who later developed the BINAP asymmetric hydrogenation catalysts for which he received the 2001 Nobel Prize in Chemistry [7[. 

Asymmetric cyclopropanation. Three laboratories have reported that copper complexes of chiral bis(oxazolines) are effective catalysts for asymmetric cyclopropanation of alkenes with diazoacetates. Bis(oxazolines) such as 1 are readily available by condensation of a-amino alcohols with diethyl malonate followed by cyclization, effected with dichlorodimethyltin or thionyl chloride. Cyclopropanation of styrene with ethyl diazoacetate catalyzed by copper complexes of type 1 indicates... 

Highly efficient catalytic asymmetric cyclopropanation can be effected with copper catalysts complexed with ligands of type 2.3 These bis(oxazolines) are prepared by reaction of dimethylmalonyl dichloride with an a-amino alcohol. As in the case of ligands of type 1, particularly high stereoselectivity obtains when R is /-butyl. Cyclopropanation of styrene with ethyl diazoacetate catalyzed by copper complexed with... 

The copper(l) triflate complex of 1 has been evaluated in the asymmetric cyclopropanation of styrene with ethyl diazoacetate (eq 3). The trans- and cis -2-phenylcyclopropane carboxylates were isolated in 88% yield as a 70 30 ratio of diastereomers in 43% and 44% enantioselectivity. These enantioselectivities are not as high as observed with other bis(oxazoline) ligands. 

Table 7.11 Asymmetric cyclopropanation of styrene with ethyl diazoacetate catalyzed by bisoxazoline-copper complexes in an ionic liquid.

Aryl-5,5-bis(oxazolin-2-yl)-l,3-dioxanes 169 have been easily prepared in three steps from diethyl bis(hydroxymethyl)malonate, amino alcohols, and aromatic aldehydes. They have been used for the copper-catalyzed asymmetric cyclopropanation of styrene with ethyl diazoacetate in up to 99% ee for the trawx-cyclopropane (maximum transicis ratio = 77/23) <05TA1415>. The same reaction performed on 2,5-dimethyl-2,4-hexadiene with tert-butyl diazoacetate in the presence of copper catalysts bearing ligand 170, prepared from arylglycines, exhibited remarkable enhancement of the rrawx-selectivity (transicis ratio = 87/13), with 96% ee for the trans product <05JOC3292>. 

Given the significant existing knowledge-base in asymmetric catalytic cyclo-propanation (Chap. 16), the discovery that metal ions useful for catalysis of carbene transfer to alkenes were also effective for nitrene transfer to the same substrates opened a clear new direction for research in asymmetric aziridination. Brief mention of the asymmetric catalysis of the aziridination of styrene was made in two early reports on (bisoxazoline)copper-catalyzed asymmetric cyclopropanations [20,21], and subsequently new methods for copper-catalyzed asymmetric aziridination were revealed in two independent studies published simultaneously by Jacobsen and Evans [22,23]. 

Similar to semicorrin ligands, chiral bis(4,5-dihydro-2-oxazolyl) systems 3 are used in copper-catalyzed asymmetric cyclopropanation of styrene with diazoacetates57 61, 9 ". In a similar way. bis(oxazolinyl)pyridine type ligands have also been used100. 

Asymmetric Cyclopropanation of Styrene. New chiral copper catalysts A or B bearing secondary 1,2-diamine ligands (eq 29) were obtained from Cu(OTf)2 (1 mol%), and 1S,2S)-N,N-di(mesitylmethyl)-l,2-diphenyl-l,2-ethanediamine (2-3 mol%), depending upon the molar ratio of ligand to Cu(OTf)2 employed. 

Catalytic, enantioselective cyclopropanation enjoys the unique distinction of being the first example of asymmetric catalysis with a transition metal complex. The landmark 1966 report by Nozaki et al. [1] of decomposition of ethyl diazoacetate 3 with a chiral copper (II) salicylamine complex 1 (Scheme 3.1) in the presence of styrene gave birth to a field of endeavor which still today represents one of the major enterprises in chemistry. In view of the enormous growth in the field of asymmetric catalysis over the past four decades, it is somewhat ironic that significant advances in cyclopropanation have only emerged in the past ten years. 

Bis-oxazoline ligands can also be produced by oxidative coupling of the copper derivative of diastereoisomerically pure 306 (Scheme 145) . Further lithiations of the product 317, which was produced as single diastereoisomer, occur (as in Scheme 143) at the second site adjacent to the oxazoline, giving, for example, 318, despite the (presumably) less favourable stereochemistry of the lithiation step. Bisoxazolines 318 direct the asymmetric copper-catalysed cyclopropanation of styrene using diazoacetate. 

Enantioselective carbenoid cyclopropanation of achiral alkenes can be achieved with a chiral diazocarbonyl compound and/or chiral catalyst. In general, very low levels of asymmetric induction are obtained, when a combination of an achiral copper or rhodium catalyst and a chiral diazoacetic ester (e.g. menthyl or bornyl ester ) or a chiral diazoacetamide ° (see Section 1.2.1.2.4.2.6.3.3., Table 14, entry 3) is applied. A notable exception is provided by the cyclopropanation of styrene with [(3/ )-4,4-dimethyl-2-oxotetrahydro-3-furyl] ( )-2-diazo-4-phenylbut-3-enoate to give 5 with several rhodium(II) carboxylate catalysts, asymmetric induction gave de values of 69-97%. ° Ester residues derived from a-hydroxy esters other than ( —)-(7 )-pantolactone are not as equally well suited as chiral auxiliaries for example, catalysis by the corresponding rhodium(II) (S )-lactate provides (lS, 2S )-5 with a de value of 67%. 

With the chiral bis(semicorrinato)copper(II) complex 9 developed by Pfaltz, enan-tioselectivities for cyclopropanes from monosubstituted alkenes are significantly higher than with Aratani s catalysts. Again, enantiocontrol can be increased by utilizing bulky diazoacetic esters (see Houben-Weyl, Vol.E19b, plll2). For menthyl diazoacetate and alkenes such as styrene, hept-l-ene, buta-1,3-diene and penta-1,3-diene, de values of 92-97% have been obtained. However, cyclopropanation of 1,2-disubstituted and trisubstituted alkenes occurs with lower chemical yield and asymmetric induction when catalyst 9 rather than 7 (R = Me) was used. ... 

Raney nickel, modified by free tartaric acids 2.69 (R = H) or their salts, has frequently been used as a catalyst for asymmetric hydrogenations of carbonyl compounds [578,948]. Several industrial applications have been described [578, 811, 812], Neveriess, hydrogenations of prochiral carbon-carbon double bonds in the presence of such catalysts gives disappointing results [578], The use of tartrate-modified copper catalysts in cyclopropanation of styrenes by diazoketones takes place with a modest asymmetric induction [578,936]. 

Asymmetric versions of copper-catalyzed cyclopropanations constitute the first examples of transition metal catalyzed asymmetric C —C bond formation37. These initial examples gave optically active cyclopropane products with only 6-8% ee by the conversion of styrene with ethyl diazoacetate, or ( i )-l -phenyl-l-propenc with diazomethane, in the presence of a chirally modified copper catalyst containing -(a-methylbenzytysalicylaldimine37- 3S. 

More recently, a number of new ideas for asymmetric induction in cyclopropanation have been reported. The concept of ion pairing of a chiral anion 13 with a copper cation was implemented in the cyclopropanation of styrene and EDA with moderate enantioselectivity as a result (73). Supramolecular-catalyzed cyclopropanation with a double helix based on ligand 14 (R = raBu) and copper(I) ions gave high enantioselectivity (74). 

Asymmetric Aziridination. A chiral, nonracemic bis(oxazo-line) complex of copper(I) triflate catalyzes asymmetric aziridination of styrene in good yield (eq 10). However, enantioselectivity is not as high as the corresponding cyclopropanation (eq 8). 

The first asymmetric copper-catalyzed cyclopropanation using a homogeneous catalyst was reported by Noyori in 1966 [31], This reaction, which allowed the cycloaddition on styrene, was carried out with a chiral Schiff base copper complex and produced poor enantiomeric excess (Fig. 11). Further refinement of the chiral ligands produced later much better catalysts, such as the bis-oxazoline (Box) derivatives, able to provide enantioselectivities up to 99%. 

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