Chiral Lewis base catalyst

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. 

Keywords Allylation, Allylsilanes, Allylstannanes, Carbonyl compounds, Chiral Lewis acid catalysts, Chiral Lewis base catalysts... 

Catalytic asymmetric allylations of aldehydes or ketones are roughly classified into two methods, namely, those using chiral Lewis acid catalysts and those using chiral Lewis base catalysts. The former method uses less reactive allylsilanes or allylstannanes as the allyl source. The latter method requires allyltrichlorosi-lane or more reactive allylmetals. Both processes are applicable to the reactions with substituted allylmetal compounds or propargylation. 

Many noticeable examples of chiral Lewis base catalyzed allylation of carbonyl compounds have also appeared. Iseki and coworkers published a full paper on enantioselective addition of allyl- and crotyltrichlorosilanes to aliphatic aldehydes catalyzed by a chiral formamide 28 in the presence of HMPA as an additive [41]. This method was further applied to asymmetric allenylation of aliphatic aldehydes with propargyltrichlorosilane [40]. Nakajima and Hashi-moto have demonstrated the effectiveness of (S)-3,3 -dimethyl-2,2 -biquinoline N,AT-dioxide (29) as a chiral Lewis base catalyst for the allylation of aldehydes [42]. In the reaction of (fs)-enriched crotyltrichlorosilane (54 , E Z=97 3) with benzaldehyde (48), y-allylated anfi-homoallylic alcohol 55 was obtained exclusively with high ee while the corresponding syn-adduct was formed from its Z isomer 54Z (fs Z= 1 99) (Scheme 6). Catalytic amounts of chiral urea 30 also promote the asymmetric reaction in the presence of a silver(I) salt, although the enantioselectivity is low [43]. 

Chiral bidentate imidodiphosphoric tetramide 33 [46], chiral 2,2 -bipyrid-ine-type N-monoxide (PINDOX) 34 [47], and chiral 3,3 -bis(hydroxymethyl)-6,6 -diphenyl-2,2 -bipyridine N,N -dioxide (35) [48] have been also developed as efficient chiral Lewis base catalysts for the asymmetric allylation of aldehydes with allyltrichlorosilane. 

Catalytic enantioselective allylations of aldehydes already published can be classified into two methods carried out under the influence of chiral Lewis acid catalysts and chiral Lewis base catalysts. The process by chiral Lewis acid catalysts generally uses allyltrimethylsilane or allyltrialkylstannane as an allylating agent, both of which show low reactivity toward aldehydes without these catalysts. The process by chiral Lewis base catalysts employs allyltrichlorosilane or allylmetals possessing relatively higher reactivity. Both processes can be successfully applied to various substituted allylmetal compounds or allenylmetal compounds. 

Iseki et al. later improved the catalytic process and showed that chiral phos-phoramides 15,16, and 17, prepared from (S)-proHne, are suitable to catalyze the asymmetric allylation of aromatic aldehydes to give chiral homoallylic alcohols 34 with up to 88% ee (Scheme 13) [36,37]. The same group has also developed a chiral formamide 18 as a chiral Lewis base catalyst [38]. This catalyst is convenient for the allylation of aUphatic aldehydes with high enantioselectivity. A typical aromatic aldehyde, benzaldehyde, gives a low enantiomeric excess (Scheme 13). 

Most recent studies from this group have extended the substrate scope to include a-acetoxy-(3-enamino esters [44]. In order to perform the reaction on those substrates they developed a novel class of chiral Lewis base catalysts, prepared from readily available chiral source (Scheme 15.16). A wide variety of A-aryl (3-aryl and heteroaryl substrates were reduced in good yields (up to 98%) and selectivity (up to 99 1 syn anti and 99% ee). The generation of Brpnsted acid that promoted... 

The asymmetric hydrosilylation of synthesized a-acetoxy-y3-enamino esters proceeded smoothly in the presence of a chiral Lewis base catalyst, (282), to provide a wide range of chiral a-acetoxy jS-amino acid derivatives in high yields with good diastereoselectivities and enantioselectivities." ° ... 

Besides chiral amines, also phosphines, sulfides, A(-heterocyclic carbenes (NHCs), phosphoramides, and form-amides have been impressively utilized as chiral Lewis base catalysts in numerous case studies [14, 88]. Chiral phosphines have been mainly used for BayUs-Hillman-type reactions and allenoate activations in this context [88, 94]. 

SCHEME 6.35 Exemplified reports illustrating the use of chiral Lewis base catalysts for the activation of Lewis acids. 

The Lewis base-catalyzed reactions oftrichlorosilyl-protected carbon nucleophiles are important as silicon Lewis acid-promoted reactions. This review, however, does not deal with these topics because of the limited space and the availabihty of recent reviews [2, 38-40]. Denmark and coworkers have recently succeeded in enantioselective reactions using SiCU and chiral Lewis base catalysts, which are detailed in this section. 

This class of chiral Lewis base catalysts was also applicable to the enantioselective aldol reactions of trichlorosilyl enol ethers (Scheme 7.14) [24, 25). As included in Scheme 7.14, Denmark devised chiral bipyridine N.N -dioxide 8 and demonstrated that it smoothly catalyzed the aldol addition of methyl acetate-derived trichlorosilyl ketene acetal to a series of ketones with good to high enantioselectivi-ties [25],... 

The potential of 9 as a chiral Lewis base catalyst was further demonstrated by application to the aldol reaction of trichlorosilyl enol ethers of ketones with aldehydes, which proceeded with high diastereo- and enantioselectivity [32], The observed stereospecificity suggested the intervention of a six-membered cyclic transition state (Scheme 7.17). Notably, enoHzation of cyclohexanone derivatives and aliphatic aldehydes appeared feasible by SiCLt with the assistance of amine base and 9, leading to the estabhshment of a new protocol for direct aldol-type reactions between ketones and aldehydes or two aldehydes (Scheme 7.18) [33]. 

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