Styrenes asymmetric cyclopropanations

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). 

Woo et al. [54] prepared new chiral tetraaza macrocyclic hgands (48 in Scheme 23) and their corresponding iron(II) complexes and tested them, as well as chiral iron(II) porphyrin complexes such as Fe (D4 -TpAP) 49, in asymmetric cyclopropanation of styrene. 

In 2004, ruthenium-catalysed asymmetric cyclopropanations of styrene derivatives with diazoesters were also performed by Masson et al., using chiral 2,6-bis(thiazolines)pyridines. These ligands were prepared from dithioesters and commercially available enantiopure 2-aminoalcohols. When the cyclopropanation of styrene with diazoethylacetate was performed with these ligands in the presence of ruthenium, enantioselectivities of up to 85% ee were obtained (Scheme 6.6). The scope of this methodology was extended to various styrene derivatives and to isopropyl diazomethylphosphonate with good yields and enantioselectivities. The comparative evaluation of enantiocontrol for cyclopropanation of styrene with chiral ruthenium-bis(oxazolines), Ru-Pybox, and chiral ruthenium-bis(thiazolines), Ru-thia-Pybox, have shown many similarities with, in some cases, good enantiomeric excesses. The modification... 

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. 

For example, the asymmetric cyclopropanation of styrene with BDA catalyzed by CuOTf 83 yields cyclopropane with a trans cis ratio of 94 6 and 99% ee for the trans-isomer.31... 

Suga et al. (63) reported the asymmetric cyclopropanation of styrene using chiral binaphthyl-derived diimines. Diastereoselectivities and enantioselectivities in the cyclopropanation of styrene are moderate, Eq. 45. Improved selectivities are observed using 1,1-diphenylethene, which provides the men thy 1 ester cyclopropane in 96% de. 

The glyoxime-Co(II)-catalyzed asymmetric cyclopropanation shown in Scheme 94 is noteworthy (226). The results of the detailed kinetic study are consistent with the mechanism of Scheme 92, however, the intermediary Co carbenoid species has substantial radicaloid properties, and only styrene and other conjugated olefins can be used as substrates. Simple alkenes are not cyclopropanated by diazo compounds. The reaction of deuterated styrene proceeds in non-stereospecific manner without retention of geometrical integrity. 

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[. 

Novel chiral Robson-type tetraimine macrocyclic complexes with Co(II), Co(III), Mn(II), and Mn(III) have been synthesized by metal template condensation of 2,6-diformyl-4-methylphenol with (l/f,2/f)-diaminocyclohexane or (lR,2R)-diphenyl-ethylenediamine. The dinuclear Co(II) and Co(III) complexes were shown to catalyse asymmetric cyclopropanation of styrene with diazoacetate cooperatively and with high enantioselectivity.118... 

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... 

Chiral pybox ligands were synthesized as ligands for the asymmetric cyclopropanation of styrene.10 In-pybox ligand 3 was prepared by reaction of 1 with 2,6-pyridine dicarbonyl dichloride in the presence of potassium hydrogen carbonate in isopropyl acetate followed by cyclization of the fcA-hydroxyamide with BF3 OEt2 at 120°C.22... 

Zhang s group developed highly active chiral (porphyrin)cobalt(II) complexes 327b-d, which catalyzed the cyclopropanation reactions of styrenes [356-358] and even of ot,(3-unsaturated esters or nitriles [358, 359] by diazoacetates. Nitrodi-azoacetates [360] or sulfonyldiazomethane [361] also proved to be useful in asymmetric cyclopropanation reactions of styrenes, acrylic derivatives, and in some cases even simple olefins with good to high de and moderate to excellent ee (highlight [362]). 

A number of reports on the use of bis[(45)-(l-methylethyl)-oxazolin-2-yl]methane in the asymmetric cyclopropanation of styrene have been reported (eq 3, Table 1). Although the yields of the cyclopropanes are good, the enantioselectivities are not as high as those observed with other bis(oxazoline) ligands. ... 

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 7.1 Catalytic asymmetric cyclopropanation of styrene and diazoacetates with Ru-Pybox catalysts.

It is worth recalling that the asymmetric cyclopropanation of styrene with ethyl diazoacetate, reported in 1966 by Noyori and co-workers, appears to be the first example of transition metal catalyzed enantioselective reaction in homogeneous phase. This reaction remains a landmark in asymmetric cyclopropanation. On a general standpoint, catalytic asymmetric cyclopropanation continues to attract much attention, due in part to the marked trends toward marketing more and more optically active molecules as the optically pure eutomer. This topic has been much studied in connection, inter alia, with the synthesis of valuable intermediates such as chrysanthemic acid derivatives and cilastatin. The subject has been recently reviewed [17]. 

Following Nishiyama s original discovery of an efficient chiral ligand (full name of Pybox) Pybox [137], many chiral complexes have been synthesized and utihzed as catalysts in a variety of asymmetric transformations. Asymmetric cyclopropanation is one such application which uses the Pybox-Ru catalyst [138]. A polymer-supported version ofthe Pybox-Ru complex 218 was prepared by copolymerization of the chiral monomer 217 with styrene and DVB, followed by treatment of the resulting polymer with [RuCl2(p-cymene)]2 in CH2CI2 (Scheme 3.72) [139]. The corresponding ruthenium complexes catalyzed the cyclopropanation reaction of... 

Another type of polymer-supported chiral catalyst for asymmetric cyclopropanation was obtained by electropolymerization of the tetraspirobifluorenylporphyrin ruthenium complex [143]. The cyclopropanation of styrene with diazoacetate, catalyzed by the polymeric catalyst 227, proceeded efficiently at room temperature with good yields (80-90%) and moderate enantioselectivities (up to 53% at -40 °C) (Scheme 3.75). PS-supported versions of the chiral ruthenium-porphyrin complexes 231 (Scheme 3.76) were also prepared and used for the same reaction [144]. The cyclopropanation of styrene by ethyl diazoacetate proceeded well in the presence of the polymeric catalyst to give the product in good yields (60-88%) with high stereoselectivities (71-90% ee). The highest ee-value (90%) was obtained for the cyclopropanation of p-bromostyrene. 

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

A ruthenium carbene complex in the presence of a chiral ligand is capable of catalyzing the formation of optically active cyclopropane derivatives from alkenes and diazo compounds in high enantiomeric excess [177]. A mixture of [RuCl2(/ -cymene)] in the presence of pybox-(5,5)-/ catalyzes the asymmetric cyclopropanation of styrene (eq (48)). The key intermediate is proposed to be a dichloro(pybox)ruthenium carbene complex. 

Scheme 8 The asymmetric cyclopropanation of styrene with the chiral trans-TpP ligand...

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>. 

Cilastatin 147 is used to increase the potency of P-lactam antibiotics. It is manufactured commercially by asymmetric cyclopropanation of isobutylene with ethyl diazoacetate catalysed by the Aretani Cu(I) complex 143 that is more effective with this trisubstituted alkene than with styrene.34... 

Davies and co-workers [12, 35] have exploited one particular aspect of the asymmetric cyclopropanation of alkenes with vinyl diazoacetates, namely, application to substrates suitable for subsequent Cope rearrangement. Cyclopropanation of dienes with predominant cfs-1,2-divinyl diastereoselection makes possible subsequent facile [3,3]-sigmatropic rearrangement with entry to 1,4-cycloheptadienes or bicyclic dienes. Two such examples employing cyclopenta-diene and penta-l,3-diene as substrates and the rhodium(II) prolinate catalyst, Rh2(2S-TBSP)4 in Fig. 1, are shown in Eq. (6) and Eq. (7),respectively cfs-l,2-di-vinylcyclopropanes are presumed to be intermediates in these annulation reactions. In contrast, ethyl diazoacetate and styrene with the prolinate catalyst (Fig. 

Recently, another cobalt(II)/camphor-derived complex was developed for performing the asymmetric cyclopropanation of olefins [38]. The complex 18 was prepared by reacting the ligand 17, synthesized by condensation of (lR)-3-hydroxymethylenebornane-2-thione and the corresponding diamine, with co-balt(II) dichloride hexahydrate in degassed ethanol (Scheme 11). The cyclopropane derivatives were obtained in 50-60% yield using 3 mol % of the catalyst 18 and ethyl diazoacetate in styrene or 1-octene as solvent. The diastereomeric ratios were low for both styrene and 1-octene. 

More recently, Katsuki and coworkers have shown that (salen)Co(III) bromide 23 is an efficient catalyst for the asymmetric cyclopropanation of styrene derivatives [39,40,41]. The Co(III)-salen complex 23 was obtained from the oxidation of the corresponding Co (II)-salen complex 22 by bromine (Scheme 12). The Co(II)-salen complex 22 was synthesized from Co(OAc)2 and the corresponding salen ligand 21 which, in turn, was prepared from (1R,2R)-... 

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