Lewis-base asymmetric

The Staudinger reaction [92], a [2 + 2]-cycloaddition of a ketene and a nucleophilic imine, usually proceeds by an initial imine attack on the ketene thus forming a zwitterionic enolate which subsequently cyclizes. This reaction is an expedient route to p-lactams, the core of numerous antibiotics (e.g., penicillins) and other biologically active molecules [93]. In contrast, for Lewis-base catalyzed asymmetric reactions, nonnucleophilic imines are required (to suppress a noncatalyzed background reaction), bearing, for example, an N-Ts [94] or -Boc-substituent [95]. 

Other reactions not described here are formal [3 -i- 2] cycloadditions of a,p-unsaturated acyl-fluorides with allylsilanes [116], or the desymmetrization of meso epoxides [117]. For many of the reactions shown above, the planar chiral Fe-sandwich complexes are the first catalysts allowing for broad substrate scope in combination with high enantioselectivities and yields. Clearly, these milestones in asymmetric Lewis-base catalysis are stimulating the still ongoing design of improved catalysts. 

Further work by the Ye group has shown that NHCs derived from pre-catalyst 215 can also promote the asymmetric dimerisation of alkylarylketenes 193 to generate alkylidene P-lactones 216 in good diastereo- and enantio-selectivity [83], The asymmetric [4+2] addition of enones and alkylarylketenes to generate 8-lactones 218 in high ee has also been accomplished [84], as has the asymmetric esterification of alkylarylketenes to give esters 217 using benzhydrol, which is assumed to proceed via a Lewis-base mediated mechanism (Scheme 12.46) [85]. 

A yyw-selective asymmetric nitro-aldol reaction has been reported for structurally simple aldehydes using a new catalyst generated from 6,6-bis[(triethylsilyl)ethynyl]BINOL (g in Scheme 3.18).126 The syn selectivity in the nitro-aldol reaction can be explained by steric hindrance in the bicyclic transition state as can be seen in Newman projection. In the favored transition state, the catalyst acts as a Lewis acid and as a Lewis base at different sites. In contrast, the nonchelation-controlled transition state affords anti product with lower ee. This stereoselective nitro-aldol reaction has been applied to simple synthesis of t/ircodihydrosphingosine by the reduction of the nitro-aldol product with H2 and Pd-C (Eq. 3.79). 

Recently, novel bifunctionalized zinc catalysts have been developed (compounds (N) and (P), Scheme 55). They have both Lewis-acid and Lewis-base centers in their complexes, and show remarkable catalytic activity in direct aldol reactions.233-236 A Zn11 chiral diamine complex effectively catalyzes Mannich-type reactions of acylhydrazones in aqueous media to afford the corresponding adducts in high yields and selectivities (Scheme 56).237 This is the first example of catalytic asymmetric Mannich-type reactions in aqueous media, and it is remarkable that this chiral Zn11 complex is stable in aqueous media. 

Additions to quinoline derivatives also continued to be reported last year. Chiral dihydroquinoline-2-nitriles 55 were prepared in up to 91% ee via a catalytic, asymmetric Reissert-type reaction promoted by a Lewis acid-Lewis base bifunctional catalyst. The dihydroquinoline-2-nitrile derivatives can be converted to tetrahydroquinoline-2-carboxylates without any loss of enantiomeric purity <00JA6327>. In addition the cyanomethyl group was introduced selectively at the C2-position of quinoline derivatives by reaction of trimethylsilylacetonitrile with quinolinium methiodides in the presence of CsF <00JOC907>. The reaction of quinolylmethyl and l-(quinolyl)ethylacetates with dimethylmalonate anion in the presence of Pd(0) was reported. Products of nucleophilic substitution and elimination and reduction products were obtained . Pyridoquinolines were prepared in one step from quinolines and 6-substituted quinolines under Friedel-Crafts conditions <00JCS(P1)2898>. 

As an alternative approach, chiral Lewis base has been tested for catalytic allylation. Compound 139, reported by Iseki et al.,88 was the first example of a chiral Lewis base that effectively serves as a catalyst in asymmetric allylation in combination with HMPA. Allylation of aliphatic aldehydes with allyl- and crotyltrichlorosilanes in the presence of 139 provides up to 98% ee (Scheme 3-49). 

Another example is the asymmetric cyanosilylation of aldehydes catalyzed by bifunctional catalyst 131.100 Compound 131 contains aluminum, the central metal, acting as a Lewis acid, and group X, acting as a Lewis base. The asymmetric cyanosilylation, as shown in Scheme 8-50, proceeds under the outlined... 

Bifunctional Asymmetric Catalysis Promoted by Chiral Lewis Acid -Lewis Base Complexes... 

A review of enantioselective aldol additions of latent enolate equivalents covers a variety of Sn", boron, Ti, Cu, lanthanide, and Lewis base catalysts. Asymmetric aldol reactions using boron enolates have been reviewed (401 references). ... 

Not only cyanide but also an isocyanide behaves as a nucleophile to attack a carbonyl compound or an imine that is prepared in situ from an carbonyl compound. " In these reactions, an isocyanide is a synthetic equivalent to an aminocarbonyl anion. Asymmetric version of this reaction appeared in 2003. Using a combination of Lewis acid SiCU and a Lewis base chiral bisphosphora-mide, the corresponding a-hydroxyamide is obtained in 96% yield with >98% ee (Scheme 4.23). 

Asymmetric addition of small-molecule nucleophiles to carbonyl groups and their derivatives are catalyzed by either Lewis acids or Lewis bases. Carbon dioxide is now a promising building block for as5mimetric organic synthesis. 

In addition to metal catalysts, organocatalysts could also be used in asymmetric cyanation reactions. Chiral Lewis bases, modified cinchona alkaloids, catalyzed asymmetric cyanation of ketones by using ethyl cyanoformate as the cyanide source (Scheme 5.34)." Similar to metal-catalyzed reactions, ethyl cyanoformate was first activated by chiral Lewis bases to form active nucleophiles. Various acyclic and cyclic dialkyl ketones were transformed into the desired products. Because of using... 

Two patterns are possible in the activation mechanism by simple chiral Lewis base catalysts. One is through the activation of nucleophiles such as aUyltrichlorosilanes or ketene trichlorosilyl acetals via hypervalent silicate formation using organic Lewis bases such as chiral phosphoramides or A-oxides. " In this case, catalysts are pure organic compounds (see Chapter 11). The other is through the activation of nucleophiles by anionic Lewis base conjugated to metals. In this case, transmetal-lation is the key for the nucleophile activation. This type of asymmetric catalysis is the main focus of this section. 

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