Semicorrin ligands cyclopropanation

Subsequently, bis(oxazoline) ligands ((70) and (71)), structurally related to the semicorrin ligand, were introduced and further expanded the scope of asymmetric cyclopropanation... 

The next major contribution in asymmetric cyclopropanation was the introduction of chiral semicorrin ligands 184 by Fritschi et al.95 This ligand has been used for coordinating with copper and has been found to provide improved enantiocontrol in the cyclopropanation of monosubstituted olefins. Copper(I), coordinated by only one semicorrin ligand, is believed96 to be the catalytically active oxidation state. The copper(I) oxidation state can be reached directly... 

A remarkable complex (33) with a C2-symmetric semicorrin ligand has been recently developed by Pfaltz and coworkers.64 A copper(II) complex was used as a procatalyst, but (33) was shown to be the active cyclopropanation catalyst. As shown in Table 3, this complex resulted in spectacular enantioselecti-vities in the range of 92-97% ee. Once again, the (15,35,4/ )-menthyl group attenuated the selectivity. Unfortunately, even though respectable yields were obtained with dienes and styrenes, the reaction with 1-heptene was rather inefficient. 

Cu complexes with bis-oxazoline ligands 6 that were first reported by Masamune and co-workers [39] have incited considerable interest because of the exceptional enantiocontrol that can be achieved with their use as catalysts for cyclopropanation reactions. Concurrent investigations by Evans [40], who added 7 Masamune, who provided 8 and 9 [41] and Pfaltz [42], who investigated a similar series, established that the C2-symmetric bis-oxazoline ligands are suitable alternatives to semicorrin ligands for Cu in creating a highly enantioselective environment for intermolecular cyclopropanation. For the first time, diazoacetates with ester substituents as small as ethyl could be used to achieve enantioselectivity >90% ee in reactions with styrene (Table 5.4). 

Intramolecular cyclopropanations with unsaturated diazo ketones have also been reported. Furthermore, enantioselective cyclopropanation with diazomethane can be achieved in up to 75% ee. In detailed mechanistic discussions, a copper(I) species, complexed with only one semicorrin ligand, and formed by reduction and decomplcxation, is suggested as the catalytical-ly active species, cisjtrans Stereoselection and discrimination of enantiotopic alkene faces should take place within a copper-carbene-alkene complex25-54"56. According to these interpretations, cisjtrans selectivity is determined solely by the substituents of the alkene and of the diazo compound (especially the ester group in diazoacetates) and is independent of the chiral ligand structure (salicylaldimine or semicorrin)25. 

Semicorrin ligands have also been used in asymmetric cyclopropanation of silyl enol ethers to give optically active silyloxycyclopropanes which, after acid-catalyzed ring opening, serve as convenient precursors in the synthesis of chiral y-oxo carboxylic esters50. 

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. 

After the introduction of chiral Schiff base and semicorrin ligands as enan-tioselective copper catalysts, the next major advance in copper systems is based on bis(oxazoline) ligand 7 (65) and 8 (66) (Scheme 11). With 7, up to 99% ee of cyclopropane was obtained for the cyclopropanation of styrene with EDA. Same enantioselections but higher diastereoselectivity (transrcis = 94 6) was obtained when 2,6-di-Zert-butyl-4-methylphenyl diazoacetate (BDA) was used instead of EDA. It was noted that the catalytic system with 7 was the only copper sys-... 

Chiral C2-symmetric semicorrins (structure 4), developed by Pfaltz [11], were proven to be highly efficient ligands for the copper-catalyzed enantio-selective cyclopropanation of olefins. Variations of the substituents at the stereogenic centers led to optimized structures and very high enantioselectiv-ities [12]. 

Asymmetric cyclopropanations of alkenes and alkynes with a-diazocarbonyl compounds have been extensively explored in recent years and a number of very effective chiral catalysts have been developed2. Copper complexes modified with such chiral ligands as salicy-laldimines 38202,203, semicorrins 39204 208, bis(oxazolines) 40209-2" and bipyridines 41212 have... 

For the cyclopropanation of terminal mono- and disubstituted alkenes, the cationic Cu complex derived from ligand (1) is clearly the most efficient catalyst available today, giving consistently higher enantiomeric excesses than related neutral semicorrin or bisoxazoline Cu complexes of type (3), - which can induce enantiomeric excesses of up to 92% ee in the cyclopropanation of styrene with ethyl diazoacetate. High enantioselectivities, ranging between the selectivities of the Evans catalyst (eq 3) and complex (3) (M = Cu, R = t-Bu), have also been observed with cationic Cu complexes of azasemicorrins. ... 

Although many different bisoxazolines and other semicorrin-type ligands have been prepared [53,54], the bis(ferf-butyl)oxazoline 11 is still the most versatile ligand for cyclopropanation. However, there are certain applications which give better results with other ligands. For the cyclopropanation of trisubstituted and 1,2-disubstituted (Z)-olefins, Lowenthal and Masamune found the bisoxa-zoline 12 to be superior to the bis(ferf-butyloxazoline) 11 [56]. This is illustrated by the reaction of 2,5-dimethyl-2,4-hexadiene leading to chrysanthemates (Scheme 9). Again, the best diastereo- and enantioselectivities were obtained with bulky diazoacetates. Both the trans/cis ratios and ees were similar to those reported for Aratani s catalyst (Scheme 5). 

Copper-Catalyzed Asymmetric Cyclopropanation with Chiral Semicorrin and Related Ligands... 

Enantioselective cyclopropanation and allylic alkylation These semicorrins, particularly when treated with CuOTf, are comparable to bis(oxazoline) ligands (16, 38-41) for cyclopropanation. 

The obvious first test of methylene-bis(oxazolines) 6 was the copper-catalyzed cyclopropanation. Among the various derivatives that we had prepared (6 R = benzyl, c-alkyl, phenyl, tert-hutyl the bulky t rt-butyl-substituted derivative proved to be the most effective ligand, giving similarly high enantiomeric excesses as the semicorrin Ic (R = CMe20H) (Scheme 14) [25]. The same results were obtained by Masamune and coworkers in an independent parallel study [28]. More recently, Lowenthal and Masamune showed that the method works also well for certain trisubstituted and unsymmetrically disubstituted cis-olefins if the di-t rt-butyl-substituted ligand is replaced by structurally modified bis(oxazolines) [32]. 

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