Lewis base catalysts enantioselective addition

As shown above, it was not so easy to optimize the Michael addition reactions of l-crotonoyl-3,5-dimethylpyrazole in the presence of the l ,J -DBFOX/ Ph-Ni(C104)2 3H20 catalyst because a simple tendency of influence to enantio-selectivity is lacking. Therefore, we changed the acceptor to 3-crotonoyl-2-oxazolidi-none in the reactions of malononitrile in dichloromethane in the presence of the nickel(II) aqua complex (10 mol%) (Scheme 7.49). For the Michael additions using the oxazolidinone acceptor, dichloromethane was better solvent than THF and the enantioselectivities were rather independent upon the reaction temperatures and Lewis base catalysts. Chemical yields were also satisfactory. 

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). ... 

A. Enantioselective Addition of Dialkylzincs to Aldehydes using Lewis Base Catalysts... 

On the basis of their observation that achiral 2,2 -bipyridyl promotes the reaction between crotyltrichlorosilane and benzaldehyde, the Barrett group screened chiral pyridine molecules as Lewis-base catalysts for this reaction [175]. The pyridinylox-azoline 164a was identified as the most efficient organocatalyst. In the presence of this catalyst, which was, however, used in stoichiometric amounts, asymmetric addition of (E)-crotyltrichlorosilane 158b to aldehydes gave the anti products (S,S)-159 in yields of 61-91% and with enantioselectivity from 36 to 74% ee (Scheme 6.76) [175], Diastereoselectivity is high, because only the anti diastereomers were obtained. Aromatic aldehydes and cinnamylaldehyde were used as substrates. 

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]. 

Although addition of the trichlorosilyl enolate of methyl acetate to aldehydes is accelerated by a Lewis base catalyst, poor enantioselectivity is observed for the asymmetric version using 79, because of competition by the uncatalyzed achiral process (Scheme 10.30 in Section 10.2.1.4) [95]. Denmark et al. recently demonstrated that reactive silyl enolates are valuable for asymmetric addition to ketones (Scheme 10.67) [174]. The use of bis-N-oxide 80 as catalyst achieves high enantioselectivity in the reaction with aromatic ketones. 

As an efficient bifunctional catalyst, proline has been used as a Br0nsted acid in combination with a nucleophilic Lewis base catalyst in the asymmetric BH reaction. Miller and co-workers [119] disclosed that in the L-proline-catalyzed BH reaction of MVK and electron-deficient aldehydes the imidazole-tailed peptide 67 was an efficient co-catalyst. A matched/mismatched phenomenon of two chiral catalysts was observed in this reaction. Furthermore, Zhou and co-workers [120] synthesized various chiral amines and screened them as co-catalysts of L-proline in the BH reaction of MVK and aldehydes, revealing that chiral benzodiazepine 68 and aminoalcohol 69 were efficient catalysts. Interestingly, the intramolecular reaction shown in Scheme 9.34 could be directly catalyzed by L-proline in DMF solvent, while the addition of imidazole resulted in enhancement of the enantioselectivity with opposite configurational product [121]. A similar process was realized in the intramolecular reaction shown in Scheme 9.35 with 70 as co-catalyst of iV-methylimidazole. Moreover, Cordova and co-workers [122] reported in 2007 the first example of asymmetric aza-BH reaction between (3-mono- or disubstituted acroleins and aldimines. By utilizing L-proline as catalyst in combination with... 

Ishihara and coworkers also reported mixed zinc reagents, namely PhjZn/EtjZn, as the phenyl source for enantioselective phenyl additions to ketones (Scheme 7.51). The cat2ilyst was a chiral phosphoramides-Zn(II) complex prepared in situ [81]. These chiral Zn(II) cat2ilysts serve as conjugate Lewis acid-Lewis base catalysts (Figure 7.10). From a variety of aromatic and aliphatic ketones, optically active tertiary alcohols were obtained in high yields with high enantioselectivities (up to 98% ee) under mild reaction conditions (Scheme 7.51). 

It is well known that a zwitterionic enolate intermediate can be generated via the addition of a Lewis base to ketenes, which can be oxidized by an appropriate oxaziridine to form the corresponding imine and zwitterionic epoxide. The obtained zwitterionic epoxide intermediate is expected to add to the in situ generated imine to furnish the final products. Based on this finding. Ye reported a novel enantioselective formal [3 + 2] cycloaddition of ketene 40 to racemic oxaziridine 41 for the synthesis of oxazolin-4-one. By using NHC 43 or 44 as the Lewis base catalyst [23], the product 42 could be obtained in good yield with high diastereo and enantioselectivity (Scheme 2.12). 

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],... 

Shibasaki has described the use of bifunctional catalysis in asymmetric Strecker reactions, using BlNOL-derived Lewis acid-Lewis base catalyst 160 (Equation 24) [114]. The aluminum complex had previously been shown to catalyze enantioselective cyanohydrin formation (Chapter 2, Section 2.9) [115]. In the proposed catalytic cycle, the imine is activated by the Lewis acidic aluminum while TMSCN undergoes activation by association of the silyl group with the Lewis basic phosphine oxide. Interestingly, the addition of phenol as a putative proton source was beneficial in facilitating catalyst turnover. The nature of the amine employed for the formation of the N-substituted aldimine proved to be vital for enantioselectivity, with optimal results obtained for N-fluorenyl imines such as 159, derived from aliphatic, unsaturated, and aromatic aldehydes (70-96% ee) [114],... 

Quite a number of asymmetric thiol conjugate addition reactions are known [84], but previous examples of enantioselective thiol conjugate additions were based on the activation of thiol nucleophiles by use of chiral base catalysts such as amino alcohols [85], the lithium thiolate complex of amino bisether [86], and a lanthanide tris(binaphthoxide) [87]. No examples have been reported for the enantioselective thiol conjugate additions through the activation of acceptors by the aid of chiral Lewis acid catalysts. We therefore focussed on the potential of J ,J -DBFOX/ Ph aqua complex catalysts as highly tolerant chiral Lewis acid catalyst in thiol conjugate addition reactions. 

Dialkylzincs are much less reactive than phenyl or alkynylzincs. In 2002, Kozlowski et al. developed a chiral salen-based catalyst 62 that can promote the diethylzinc addition to a-ketoesters in high yield, [Eq. (13.38)]. In their catalysis, titanium acts as a Lewis acid, and amine nitrogen acts as a Lewis base (63). The enantioselectivity was up to 78% ee ... 

Allyl boronates react very slowly with carbonyl compounds as compared to the corresponding allyldialkylboranes, due to the presence of two oxygen atoms on boron which diminish the Lewis acidity of boron. However, the activity of the allyl boronates can be enhanced by the addition of Lewis acid catalysts. There have been two complementary approaches described for the stereoselective allylation with allyl boronates, one involving the use of chiral Lewis acid, and the other involving chiral allyl boronates in conjunction with achiral Lewis acid catalyst. Several chiral fVsymmetric-based 1,2-diols 197 have been employed in combination with SnCLj as a Lewis acid and excellent level of enantioselectivity has been observed for the allylation to furnish homoallylic alcohols 198 with high ee (Equation 8) <2006AGE2426>. 

Romo et al. have used Lewis acids to catalyze the formation of a-silyl-/ -lactones in their synthesis of potential inhibitors of yeast 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) synthase <1998BMC1255>. In addition to various Lewis acid catalysts, a chiral promoter based on the chiral diol (l/ ,2R)-2-[(diphenyl)hydroxymethyl]cyclo-hexan-l-ol was introduced to the reaction in an attempt to improve the stereoselectivity. A variety of chiral 2-oxetanones were formed, with enantioselectivities ranging from 22% to 85%. Dichlorotitanium-TADDOL catalysts 113 and 114 have also been used in an attempt to encourage the stereoselective [2+2] cycloaddition of silyl ketenes and aldehydes (TADDOL = (—)-/ra r-4,5-bis(diphenyl-hydroxymethyl)-2,2-dimethyl-l,3-dioxolane), although this method only afforded 2-oxetanones in moderate yields and optical purity (Equation 41) <1998TL2877>. 

Considerable effort has been devoted to the development of enantiocatalytic MBH reactions, either with purely organic catalysts, or with metal complexes. Paradoxically, metal complex-mediated reactions were usually found to be more efficient in terms of enantioselectivity, reaction rates and scope of the substrates, than their organocatalytic counterparts [36, 56]. However, this picture is actually changing, and during the past few years the considerable advances made in organocatalytic MBH reactions have allowed the use of viable alternatives to the metal complex-mediated reactions. Today, most of the organocatalysts developed are bifunctional catalysts in which the chiral N- and P-based Lewis base is tethered with a Bronsted acid, such as (thio)urea and phenol derivatives. Alternatively, these acid co-catalysts can be used as additives with the nucleophile base. 

Silver can mediate oxidation reactions and has shown unique reactivity. In a few cases, namely, nitrene-, carbene-, and silylene-transfer reactions, novel reactivity was found with homogeneous silver catalysts. Some of these reactions are uniquely facilitated by silver, never having been reported with other metals. While ligand-supported silver catalysts were extensively utilized in enantioselective syntheses as Lewis acids, disappointingly few cases were reported with oxidation reactions. Silver-catalyzed oxidation reactions are still underrepresented. Silver-based catalysts are cheaper and less toxic versus other precious metal catalysts. With the input of additional effort, this field will undoubtedly give more promising results. 

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