Chiral Lewis Acid Complexes

Evans et al. [15] reported that Cu-based catalysts were superior in the Diels-Alder reaction of the oxazolidinone 9 with cyclopentadiene 8. ITie (5,5)-bis(oxazo-line)-Cu(II) and -Zn(II) complexes were very effective catalysts of the reaction. The optimum tert-butyl ligand 13-Cu(II) complex afforded (2S)-endo-ll with 98 % ee. In contrast, the optimum catalyst system for the phenyl-substituted ligand 12-Zn complex afforded the enantiomeric (R) product, (2R)-endo-ll, with 92 % ee. The different direction of asymmetric induction was explained in terms of the geometry of cata-lyst-dienophile complexes at the corresponding metal centers. The bis(oxazoline)-Zn(II) complex-catalyzed reaction proceeded via the tetrahedral chiral Zn-dienophile complex VIII, in a manner similar to the bis(oxazoline)-Mg catalyst reported by Corey [13], whereas the reaction catalyzed by the cationic bis(oxazoline)-Cu complex proceeded via the square-planar Cu(II)-dienophile intermediate VII, so the diene preferred to approach from the opposite si face of the bound dienophile with s-cis configuration, avoiding steric repulsion by one of the tert-butyl substituents on the oxazoline rings. 

Llera et al. [17] reported a new chiral hydroxysulfoxide 15, the chiral Mgl2 complex of which catalyzed the reaction of the oxazolidinone 9 with cyclopentadiene 8 at -78 °C to give (2S)-11 in 95 % yield ( 98 % endo) with 84 % ee. They proposed two reactive species X and XI to explain the mode of asymmetric induction in the preceding reaction. Transition states X and XI differ in the arrangement of the oxazolidinone 

Takacs et al. [18] then examined a series of chiral bis(oxazohne) hgands, differing in the length of the chain connecting the chiral oxazoline moieties, using triflate complexes of Mg(II), Zn(II), and Cu(II) in the reaction of A -crotonyloxazolidinone 16 

The enantioface selectivity observed in the reaction with bis(oxazoline)-Mg(OTf)2 and -Zn(OTf)2 was the opposite of that reported by Corey [13] and Evans [15]. They explained these results by suggesting that that the triflate ligands did not become detached from the metal in the reaction medium, and that reaction proceeded via the rra 5-octahedral intermediate XII rather than the tetrahedral intermediate (Fig. 3). 

Whiting et al. [20] found the catalytic system for an aza Diels-Alder reaction by the use of a combinatorial approach to catalyst selection. When methyl glyoxylate-derived aldimine 25 was reacted with Danishefsky s diene 24 in the presence of the chiral magnesium catalyst (10 mol %), prepared in-situ from chiral diphenylethylenediamine 23, Mgl2, and 2,6-lutidine, the Diels-Alder product 26 was obtained in 64 % yield with 97 % ee (Sch. 9). 

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Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

Jorgensen has recently reported similar enantioselective reactions between N-tosylimines 107 and trimethylsilyldiazomethane (TMSD) catalyzed by chiral Lewis acid complexes (Scheme 1.32) [57, 53]. The cis-aziridine could be obtained in 72% ee with use of a BINAP-copper(i) catalyst, but when a bisoxazoline-copper(i) complex was used the corresponding trans isomer was fonned in 69% ee but with very poor diastereoselectivity. 

The two faces of the borabenzene ring of this borabenzene-oxazoline adduct are inequivalent (diastereotopic), and complexation to Cr(CO)3 occurs on the less hindered face with high diastereoselectivity (Scheme 3). This work provided the first description of an enantiopure borabenzene and of an enantiopure planar-chiral Lewis acid complex. 

For the enantioselective synthesis of chiral chromanes such as 2-213, a chiral Lewis acid complex, formed in situ from Mg(OTf)2 and 2-212, is assumed to catalyze the domino transformation of the phenols 2-210 and the p,y-unsalurated a-ke-toesters 2-211 (Scheme 2.50). 2-213 was obtained in excellent diastereoselectivity, but only in mediocre enantioselectivity. 

The most common sources of the chiral ligands employed for making a chiral Lewis acid complex are chiral diols with a C2-symmetric axis. This C2-symmetric feature reduces the number of competing transition states, which is... 

It should be noted that asymmetric acyl transfer can also be catalyzed by chiral nucleophilic A-heterocyclic carbenes [27-32] and by certain chiral Lewis acid complexes [33-37] but these methods are outside the scope of this review. Additionally, although Type I and Type II tr-face selective acyl transfer processes have been reported to be catalyzed by some of the catalysts described in this review, these also lie outside the scope of this review. 

The initial work on the asymmetric [4-1-2] cycloaddition reactions of A -sulfinyl compounds and dienes was performed with chiral titanium catalysts, but low ee s were observed <2002TA2407, 2001TA2937, 2000TL3743>. A great improvement in the enantioselectivity for the reaction of AT-sulfinyl dienophiles 249 or 250 and acyclic diene 251 or 1,3-cyclohexadiene 252 was observed in the processes involving catalysis with Cu(ll) and Zn(ii) complexes of Evans bis(oxazolidinone) (BOX) ligands 253 and 254 <2004JOC7198> (Scheme 34). While the preparation of enantio-merically enriched hetero-Diels-Alder adduct 255 requires a stoichometric amount of chiral Lewis acid complex, a catalytic asymmetric synthesis of 44 is achieved upon the addition of TMSOTf. 

Nitro compounds are also useful starting materials, because a nitro group can be readily converted to a carbonyl group or to amino functionality. Addition reactions of nitroalkane have been reported by Yamaguchi [13b], Shibasald [6a], Bako and Toke, Corey, Hanessian, and Kanemasa [21]. For example, Kanemasa used their chiral Lewis acid complex 35 for the reaction of 36 with nitromethane (Scheme 18). The reaction proceeded with the aid of the amine co-catalyst, affording the product 37 with high enantioselectivity. This system was also applicable to the reaction of malononitrile [2 le]. 

Scheme 18. Use of the Kanemasa chiral Lewis acid complex.

Achari B, Mandal SB, Dutta PK, Chowdhury C (2004) Synlett 2004 2449 Aggarwal VK, Belfield AJ (2003) Catalytic asymmetric Nazarov reactions promoted by chiral Lewis acid complexes. Org Lett 5 5075-5078 Akiyama T, Itoh J, Fuchibe K (2006c) Adv Synth Catal 348 999 Akiyama T, Itoh J, Yokota K, Fuchibe K (2004) Enantioselective Mannich-type reaction catalyzed by a chiral Brpnsted acid. Angew Chem Int Ed Engl 43 1566-1568... 

Mukaiyama and co-workers developed a chiral Lewis acid complex 15 consisting of tin (II) triflate and a chiral diamine. An aldol reaction of enol silyl ether 16 and octanal is promoted by 15 to give 17 in a highly diastereo-and enantioselective manner. The enantioface of the aldehyde is selectively activated by coordination with 15. This method is similar to method 3, in that an aldehyde-chiral Lewis acid complex can be regarded as a chiral electrophile. An advantage of method 4 over method 3 is the possible catalytic use of a chiral Lewis acid. In the reaction of Scheme 3.6, 20 mol% of 15 effects the aldol reaction in 76% yield with excellent selectivity.9... 

Kobayashi and co-workers. used zirconium-based bromo-BINOL complex for the catalytic enantioselective Mannich-type reaction. The o-hydroxyphenyl imine 3.36 chelates the Zr(IV)(BrBINOL)2 to form the activated chiral Lewis acid complex A. The ketone acetal 3.37 reacts with the Lewis acid complex A to give the complex B. The silyl group is then transferred to the 3-amino ester to form the product 3.38 and the catalyst Zr(BrBINOL)2 is regenerated, which is ready for binding with another imine molecule (Scheme 3.16). 

Sibi et al. [66] reported the first examples of highly enantioselective conjugate amine additions [67] by use of catalytic amounts of a chiral Lewis acid complex. Addition of 0-benzylhydroxyamine 87 (1.1 equiv.) to the pyrazole-derived crotonamide 86 proceeded smoothly in the presence of stoichiometric amounts of the chiral catalyst prepared from the bis(oxazoline) 50 and MgBr2 OEt2 with high enantiomeric excess (96 % ee) (Sch. 37). This conjugate addition reaction was equally effective with catalytic amounts of the chiral Lewis acid (92 % ee with 30 mol % 88 % ee with 10 mol %). A re face amine addition to the s-cis substrate bound to the chiral complex with tetrahedral- or ds-octahedral arrangements XXXII and XXXni accounts for the product stereochemistry observed (Fig. 7). 

Aggarwal, V. K., Belfield, A. J. Catalytic Asymmetric Nazarov Reactions Promoted by Chiral Lewis Acid Complexes. Org. Lett. 2003, 5, 5075-5078. 

They estimated the ene reactivity of trihaloaldehydes on the basis of the atomic charge and LUMO energy level by running an MO calculation on the aldehyde-fT" complexes as a model of aldehyde/chiral Lewis acid complexes [15J, The results from semi-empirical (MNDO and PM3) and ab initio (6-3IG ) calculations are listed in Table 1-1. 

Chiral Lewis acids combined with hydride sources like borohydride can reduce carbonyls to give one enantiomer selectively. The chiral Lewis acid complex with the carbonyl makes one face of the carbonyl more accessible to the hydride nucleophile. The chirality of the Lewis acid determines the chirality of the product. 

Furthermore, several chiral Lewis acid complexes of titanium [90-95], tin [96], rhenium [97,98], boron [99], and magnesium [100] have been employed for the preparation of chiral cyanohydrins. However, only in some cases are the enantiomeric excesses satisfactory. 

With the achievement of high stereochemical control resulting from nearly exclusive endo topography in the Lewis acid catalyzed reactions, the effect of chiral Lewis acid complexes on the enantiofacial selectivity of the cyclocondensation reaction should be documented. As an example, one can consider the cycloaddi-... 

In instances where a chiral Lewis acid complex is used in order to impart stereocontrol, several issues are at hand ... 

Radical allylations have proven to be a successful route for enantioselective carbon-carbon constructions. Typically, in arrangements where the radical intermediate is complexed to a chiral Lewis acid, one can envision either monocoordinate or multidentate binding of the chiral Lewis acid complex to the substrate. This interaction is dependent on both the substrate (number of donor atoms available) and the Lewis acid s binding capabilities. Highly successful examples of both such scenarios have been realized. 

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