BOX catalyst

Tab. 6.1 Dependence of absolute stereoselectivity on molecular sieves and counter ion in the reaction of la with 19b catalyzed by 10 mol% MgX2-Ph-BOX catalysts 20...

It should also be mentioned that in connection with the investigations on MgX2-BOX catalysts, Desimoni et al. also tested a Zn(C104)2-B0X catalyst for the 1,3-di-polar cycloaddition of a nitrone and acryloyloxazolidinone (see Scheme 6.17). Contrary to the magnesium catalysts, this zinc catalyst was exo selective as an 27 73 exojendo ratio was observed, and 84% ee of the exo isomer was obtained [51]. 

The reactions of nitrones constitute the absolute majority of metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions. Boron, aluminum, titanium, copper and palladium catalysts have been tested for the inverse electron-demand 1,3-dipolar cycloaddition reaction of nitrones with electron-rich alkenes. Fair enantioselectivities of up to 79% ee were obtained with oxazaborolidinone catalysts. However, the AlMe-3,3 -Ar-BINOL complexes proved to be superior for reactions of both acyclic and cyclic nitrones and more than >99% ee was obtained in some reactions. The Cu(OTf)2-BOX catalyst was efficient for reactions of the glyoxylate-derived nitrones with vinyl ethers and enantioselectivities of up to 93% ee were obtained. 

The Cu-BOX catalysts function as Lewis acids at the carbonyl oxygen. The chiral ligands promote facial selectivity, as shown in Figure 2.3. 

The basis of the enantioselectivity of the BOX catalysts has been probed using B3LYP/6-31G calculations.112 It has been proposed that in the case of the f-butyl... 

Entry 3 involves a catalyst derived from (/ , Trans-cyclohexane- 1,2-diamine. The square planar Cu2+ complex exposes the re face of the dienophile. As with the BOX catalysts, this catalyst has c2 symmetry. 

Scheme 10.12 gives some examples of enantioselective cyclopropanations. Entry 1 uses the W.s-/-butyloxazoline (BOX) catalyst. The catalytic cyclopropanation in Entry 2 achieves both stereo- and enantioselectivity. The electronic effect of the catalysts (see p. 926) directs the alkoxy-substituted ring trans to the ester substituent (87 13 ratio), and very high enantioselectivity was observed. Entry 3 also used the /-butyl -BOX catalyst. The product was used in an enantioselective synthesis of the alkaloid quebrachamine. Entry 4 is an example of enantioselective methylene transfer using the tartrate-derived dioxaborolane catalyst (see p. 920). Entry 5 used the Rh2[5(X)-MePY]4... 

Besides the symmetrical 1,1-disubstituted alkenes, unsym-metrical 1,1-disubstituted, 1,2-disubstituted, andmonosubstituted alkenes also react in a highly enantioselective manner in the presence of the copper(II) (5 ,.S )-r-Bu-box catalyst. 

Fraile, Mayoral, and coworkers utilized copper BOX catalysts (115), both homogeneous and immobilized on a laponite support, for their C-H insertion reactions [96], They obtained similar yields and diastereoselectivities to the Rh2(5 -DOSP)4 catalyst (up to about 3 1), but the highest enantioselectivity was 88% ee. Woo [10] and Che [83] chose to use achiral iron porphyrin catalysts. Woo obtained the products in 62-82% yield in about 3.5 1 dr, and Che in 88% yield, but only 2 1 dr. By way of comparison, Perez obtained excellent yields for this insertion reaction with EDA (95-99%) utilizing copper homoscorpionate catalysts 67a and 67b, [36, 39] but the transformations were not asymmetric. 

Under EOF, solutions of 21 and 75 were pumped through a packed bed containing the polymer-supported lanthanide-Py Box catalyst 76, and the reaction products were analyzed off-line by GC, allowing both the conversion and enantioselectivity of the cyanohydrin to be determined. Compared with standard batch protocols, the use of an EOF-based flow reactor enabled the authors to screen rapidly a series or reaction conditions and additives, while demonstrating excellent recyclability of the catalyst. 

One group of chiral catalysts consists of metal ion complexes, usually Cu +, of M-oxazolines (referred to as box catalysts). ... 

A series of a-hydroxy enones gave good results with a t-butyl BOX catalysts or its cyclopropyl analog [248]. 

Among other types of electrophilic compounds that give alkylation of indoles are alkylidene malonate esters. Jorgensen and coworkers observed 50-70% ee using a Cu(BOX) catalyst [262]. 

Questions are often asked concerning the catalytic nature of the asymmetric epoxidatlon. One notes that the present procedure calls for BOX catalyst. With very favorable substrates, one can realize complete conversion and >95% ee using as little as 2% catalyst. In the present case, the reaction stops at about 80% conversion using 2% catalyst, and almost reaches... 

The Evans copper(ll) bis-oxazoline (BOX) catalysts (7.193) and (7.194) (see Section 7.1) have also been used effectively for glyoxalate ene reactions. Even monosubstituted alkenes can be used as the ene component, where the alkene (7.195) reacts with ethyl glyoxalate (7.196) to give the a-hydroxy ester (7.197) with very high enantioselectivity. Other alkenes were also effective, providing enantiomeric excesses of over 90%, including alkene (7.198), which is converted into the ene-product (7.199). 

It should be noted that in most cases it is Cu-eatalyzed asymmetric oxidative biaryl homo-coupling reactions that are deseribed. On the contrary, successful examples of asymmetric oxidative biaryl eross-coupling reactions are rare. Habaue and co-workers discussed a highly eross-selective oxidative biaryl coupling between 3-hydroxy-2-naphthoates and 2-naphthols without ester functionality by a chiral Cu-BOX catalyst.The reactions proceed in a highly cross-eoupling selective manner with moderate enantioselectivity (up to 70% ee) (Scheme 3.7). Later, it was found that Lewis acids such as... 

The enantioselectivity of [Cu(S,S)-tBu-box](OTf)2 (13b)Claisen rearrangement is explained as follows (Fig. 2.4). The alkoxycarbonyl and ether oxygens coordinate in a bidentate fashion to the Cu (box) complexes. The square planer geometry around the copper(II) cation has been proposed and a chair-hke transition-state model is suggested. The aUyUc ether moiety should approach the vinyl ether moiety from the opposite direction of the t-Bu substituents on the box-hgand. The Cu"(box) catalyst differentiates between two enantiomeric chair-hke transition state by selective coordination of enantiotopic lone pairs on oxygen to form (S,S,pro-S)-14a. 

In section B, many examples reported by Jorgensen in 2001 of successful asymmetric 1,2-attack of electron-rich arenes onto the carbonyl moiety of an a-ketoester catalyzed by 5-10 mol % (. -Cu(OTf)2- Bu-BOX catalysts (92i-iv) were shown. During the same time period. Jorgensen also reported many examples of asymmetric thermodynamic conjugate addition of... 

Scheme 5.36 1,4-Phenylation of cyclohexen-2-one with Cu-BOX catalyst, as described by Reiser and coworkers [98].

The catalyzed version of this rearrangement is useful for the synthesis of medium and large-sized carbocycles [84]. For example, the enantioselective synthesis of carbocyclic natural product, (-)-9,10-dihydroecklonialactone B 121 was done successfully by catalytic asymmetric Claisen rearrangement of a GosteU-type aUyl vinyl ether 122 in the presence of (S,S)-Cu (box)-catalyst A to produce a chiral a-ketoester 123, as a building block unit [85]. 

To test this concept, we applied [Cu" (trisox)] complexes in the asymmetric Mannich reaction [24] of a P-ketoester with an activated JV-tosyl-a-imino ester, a reaction that had been previously reported by Jorgensen et al. [25] using chiral copper(II)-BOX catalysts (10mol%). After optimization of the reaction conditions, the reaction product was obtained with an excellent enantiomeric excess of 90% using 10 mol% of the catalyst (Table 15.2) [24a]. 

Chiral copper Lewis acids have also found broad utility in a variety of hetero Diels-Alder reactions. Examples in which the copper Lewis acid activates either the diene or dienophile component have been reported. Evans and coworkers utilized Cu(II)/BOX catalysts in hetero Diels-Alder reactions using unsaturated acyl phosphonates (272) or acyl esters as dienes (Scheme 17.62, Equation 17.8)... 

Asymmetric C—C bond-forming reactions have also been accomplished in flow. Chiral bisoxazolines (Box) are utilized in many asymmetric catalytic reactions as nitrogen-containing bidantate ligands for Lewis acidic metals as well as transition metals. Chiral Cu-Box can be utilized as a Lewis acid catalyst. Salvador et cd. investigated the enantioselective ene reaction using a polystyrene-bound Cu-Box catalyst (33) under flow conditions (Scheme 7.29) [125]. 

Cyclic BOX catalysts were examined to probe mechanistic studies (Scheme 1.109) [163]. C2-symmetric chiral hgand 234 was employed for asymmetric cyclopropanation using diazoacetate [164]. 

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