Achiral Lewis Acid-promoted Reactions

BfCgFsls, an air-stable, water-tolerant Lewis acid catalyst, is applicable to conjugate additions of SEE and KSA to a,79-unsaturated ketones as well as aldol and Mannich-type reactions of silyl enolates [29]. 

Tin-based Lewis acids such as Bu2Sn(OTf)2 [237], Bu3SnClO4 [52c], and 

The last two catalysts are particularly valuable for chemoselective addition of silyl 

The BiCl3-Znl2 catalyst system also is effective in conjugate addition of SEE at room temperature [57]. [Ir(COD)(PPh3)2]OTf activated by the hydrogen molecule works as the catalyst under slightly severe conditions (50-70 °C, more than 10 h) [240], 

Otera et al. have found that KSA bearing more substituents at the reaction site 

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Achiral Lewis Acid-promoted Reactions in Anhydrous Solvent... 

The preparation of vicinal polyol triads requires the placement of oxygen functionality at the y-position of the allylic stannane. The Lewis acid-promoted reaction of y-alkoxyallylstannanes with achiral aldehydes was first reported by Koree-da (Scheme 10-60) [98]. The reactions proceed in moderate to high yield and with good diastereoselectivity to produce the homoallylic alcohols. As in the case of simple ( )- and (Z)-138, the reactions are stereoconvergent giving rise to predominantly the syn diastereomer independently of olefin geometry. It was speculated that the reaction proceeds via an acyclic transition structure. 

Achiral Bronsted and Lewis Acid-promoted Reactions... 

Review on the ene-type addition reaction of CFs-containing compounds with achiral Lewis acid promoters Nagai, T. and Kumadaki, I. J. Synth. Org. Chem. Jpn. 1991,49, 624. 

The coupling of ketenes and imines has been reported to be catalyzed by a bifunctional system in which a chiral nucleophile was paired with an achiral Lewis acid metal salt [73, 74]. Optically enriched (3-lactam products were isolated in high yields, (Scheme 18). Among the various Lewis acids studied, such as Mg(OTf)2, Cu (MeCN)4C104, YbCL. La(OTf)3, AgOTf, Al(OTf)3, Sc(OTf)3, Zn(OTf)2,and In (OTf)3, this latter was the best overall cocatalyst for promoting the reaction. The best chiral nucleophiles used are reported in Scheme 18. 

Diels-Alder Reactions. Chiral a,p-unsaturated imides participate in Lewis acid-promoted Diels-Alder cycloaddition reactions to afford products in uniformly excellent endo/exo and endo diastereoselectivities (eq 50 and 51). Unfortunately, this reaction does not extend to certain dienophiles, including methacryloyl imides, p,3-dimethylacryloyl imides, or alkynic imides. Cycloadditions also occur with less reactive acyclic dienes with high diastereoselectivity (eq 52). Of the auxiliaries surveyed, the phenylalanine-derived oxazolidinones provided the highest diastereoselectivities. This methodology has been recently extended to complex intramolecular processes (eq 53). In this case, use of the unsubstituted achiral oxazolidinone favored the undesired diastereomer. 

The Lewis acid-promoted addition of allylic trialkylstannanes to achiral aldehydes has been demonstrated to provide syn homoallylic alcohols in high yield [71 a,b]. The relative stereochemical outcome of the reaction of simple aldehydes with 2-butenylstannanes is discussed earlier in this Chapter. Studies on the addition of al-... 

Keck [89a-c], Tagliavini [89d,e], and Yu [89f] have extensively studied the BINOL-Ti- or binol-Zr promoted reactions of achiral aldehydes with allylstan-nanes. The initial studies employed BINOL and either Ti(Oi-Pr)4 or TiCl2(0/-Pr)2 as the Lewis acid promoter in the reaction of achiral aldehydes with allyltributyl-stannane. The reaction affords good yields of the desired homoallylic alcohol with a high degree of enantioselectivity even with as little as 10 mol% of the chiral catalyst (Scheme 10-49) [89a]. The rate and turnover of the catalytic, asymmetric allylation reaction have also been optimized. It was found that when /-PrSSiMe3 is added to the reaction, a rate acceleration occurs, allowing as little as 1-2% of the catalyst to be used [89 fj. 

The Lewis acid-promoted addition of ) -alkoxyallylstannanes to achiral aldehydes was shown to proceed in high diastereoselectivity by an anti Se pathway (Scheme 10-64) [102]. An acyclic antiperiplanar transition structure (very similar to that shown in Fig. 10-3) was proposed to rationalize the stereoselectivity. When enantiomerically enriched allylstannanes are employed, the reaction proceeds in high enantio- and diastereoselectivity to give the homoallylic alcohols [102b]. The stereochemical outcome of the reaction is consistent with an anti Se pathway. 

The first report on the conceptually new asymmetric catalysis described that both a stoichiometric amount of SiCU and a catalytic amount of chiral phosphoramide (107) promote highly enantioselective allylation and propargylation of aromatic aldehydes with allyl- and allenyl-tributylstannane, respectively [41], The allylation does not proceed without (107). In the proposed mechanism, SiCU, a weak achiral Lewis acid, accepts the Lewis base (107) to form a strong chiral Lewis acid by polarization of the Si-Cl bonds. The active Lewis acid promotes the asymmetric reaction to give trichlorosilylated adducts with regeneration of (107) (Scheme 9.74). 

In 2008, Zhang et al. succeeded in a three-component cascade reaction using achiral Ru and chiral Zr catalysis [14]. Under the influence of achiral Rh(OAc)j, oxonium ylide was generated from diazo compound 37 and alcohol 38. Consequently, this reactive intermediate was trapped by aldehyde 39 through a Lewis acid-promoted enantioselective aldol-type addition, yielding the chiral building blocks 40 with high levels of stereocontrol (Scheme 9.11). It should be noted that the presence of acidic Zr catalyst can also suppress the undesired irreversible intramolecular proton transfer of the oxonium ylide to benefit reaction pathway control. 

Roles that are normally associated with metals as Lewis acids and as redox agents [4,5], can be emulated by organic compounds. This review will introduce the reader to the research field of Lewis acid organocatalysts. This field, compared to other types of organocatalysts, which are highlighted in the other chapters of this volume, is still limited. The number of asymmetric catalyzed examples is small, and the obtained enantiomeric excess is sometimes low. Therefore, this review will also cover a number of reactions promoted by achiral catalysts. Nevertheless, due to the broad variety of possible reactions, which are catalyzed by Lewis acids, this research field possesses a large potential. 

Denmark utilized chiral base promoted hypervalent silicon Lewis acids for several highly enantioselective carbon-carbon bond forming reactions [92-98]. In these reactions, a stoichiometric quantity of silicon tetrachloride as achiral weak Lewis acid component and only catalytic amount of chiral Lewis base were used. The chiral Lewis acid species desired for the transformations was generated in situ. The phosphoramide 35 catalyzed the cross aldolization of aromatic aldehydes as well as aliphatic aldehydes with a silyl ketene acetal (Scheme 26) [93] with good yield and high enantioselectivity and diastereoselectivity. 

Taddei and cowoikers reported that chiral allyltrimethylsUanes containing an optically active ligand derived from (-)-myrtenal attached to silicon (96) underwent enantioselective addition reactions with achiral aldehy s ( heme 46) to give, after acid hydrolysis, optically active homoallyl alcohols (98). A variety of Lewis acids were exanuned to optimize enantiomeric excess, and TiCU was found to be the most effective catalyst. The results of the TlCU-promoted additions are reported in Table 12. ... 

The catalytic asymmetric propargylation [108] and allenylation [109] of achiral aldehydes has been performed with high levels of enantioselection. The asymmetric propargylation promoted by the chiral Lewis acid derived from bind and Ti(0/-FT)4 are representative. Between 50 and 100 mol% of titanium is required for these reactions to go to completion (Scheme 10-70). The reaction of benzalde-hyde with allenyltributylstannane 170 and the chiral promoter produced the homo-propargylic alcohol 171 in >99% ee and 48% yield (7% of the undesired allenyl alcohol was also obtained). 

Interestingly, changing the radical trap from allylstannane to allylsilane increased the enantioselectivity of these allylations from 76% ee to 90% ee (Eq. 6) [10]. The by-product in the allylstannane reactions is tin halide, which is itself a Lewis acid which can promote achiral allylations. In addition, it was observed that a simple change in Lewis acid reversed the sense of stereoinduction. 

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