Semicorrins

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]. 

In 1986, Pfaltz et al. introduced a new type of pseudo C2-symmetrical copper-semicorrin complex (68) as the catalyst (Scheme 60).227 228 The complexes (68) are reduced in situ by the diazo compound or by pretreatment with phenylhydrazine to give monomeric Cu1 species (69), which catalyze cyclopropanation. Of the semicorrin complexes, complex (68a) (R = CMe2OH) showed the best enantioselectivity in the cyclopropanation of terminal and 1,2-disubstituted olefins.227,228,17 It is noteworthy that complex (68a) catalyzes cyclopropanation, using diazomethane as a carbene source, with good enantioselectivity (70-75% ee).17... 

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

Scheme 61).22 149 150 152 229 230 The methylene-bridged bis(oxazoline)s (70) can afford either neutral copper complexes of the semicorrin type (72) or cationic copper complexes (73). Cyclopro-panation with copper complexes of type (70) shows similar stereochemistry to that with the corresponding copper semicorrin complexes.229-231 Alternatively, bis(oxazoline) ligand (71), bearing... 

The Cu semicorrin complex (68a) has been successfully used as the catalyst for cyclization of alkenyl diazoketones, though the reactions of some substrates showed modest enantioselectivity (Scheme 74).276 Shibasaki et al. have successfully used the cyclization of diazoketone with Cu bis(oxazoline) (101) for the construction of the CD ring skeleton of phorbol.277... 

Recently, several mechanistic studies have been performed by means of calculations based on density functional theory. - Pfaltz s model proposed for asymmetric cyclopropanation using copper-semicorrin or -bis(oxazolines) complex has been supported by calculation.295 Another calculation also supports the parallel approach.296... 

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... 

Use of chiral semicorrins and related nitrogen heterocyclic compounds as chiral ligands in asymmetric catalysis has been reviewed periodically. Interested readers are referred to the review by Pfaltz.102... 

ASYMMETRIC COPPER AND COPPER(II) CATALYZED REACTIONS 5. Semicorrin Ligands... 

Pfaltz and co-workers (28) also showed that the semicorrin-derived catalyst is remarkably effective in intramolecular cyclopropanation reactions (28). Cycliza-tion of co-alkenyl diazoketones to form six-membered rings proceeds in high selectivity, while the analogous five-membered rings are somewhat more sensitive to substitution on the pendant alkene, Eqs. 16 and 17. 

Figure 3. X-ray crystal structure of Pfaltz semicorrin-copper catalyst (40). [Adapted from (31).]...

In hindsight, the development of bisfoxazolines) (box) from semicorrins seems a logical progression. It is, therefore, no surprise that these ligands were developed for this reaction independently and concurrently in three different laboratories. The finer details of catalyst optimization, however, were slightly different. 

Pfaltz and co-workers (45) reported neutral variants of the semicorrins as ligands in this reaction. These ligands, termed 5-azasemicorrins, may be readily assembled from pyroglutamic acid in high overall yields. Azasemicorrin (68) complexed to CuOTf forms an effective catalyst for this reaction exhibiting selectivities intermediate between the semicorrins and neutral bis(oxazolines) (45). 

Pfaltz and co-workers (108) reported that the allylic oxidation of cyclohexene proceeds in moderate selectivity using stoichiometric amounts of semicorrin-Cu(II) complexes. In catalytic reactions, the enantioselectivity decreased drastically. Better results were realized using bis(oxazolines) as ligands. Upon... 

Direct, controlled preparation of copper(I) complexes was achieved by Evans [7] from bisoxazolines and copper(I)triflate, which avoids the use of other methods for reduction or accidental reduction by the substrate, which may not always be efficient. When isobutene is the substrate one obtains only two enantiomers and no other products for styrene we obtain a cis and a trans product each occurring as a pair of enantiomers. We will illustrate this with styrene and the results of Pfaltz s semicorrin-copper. 

During these studies [4] it was again proven that copper(I) containing one semicorrin was the species needed and thus preparing the catalyst from Cu(I)OTf saves one molecule of ligand and avoids other problems. 

For a review on chiral semicorrin ligands in asymmetric catalysis, see Pfaltz, A. Synlett 1999,... 

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... 

---