Catalysts Lewis bases

Chiral phosphorarnides, as developed by Denmark during the late 1990s [25], are efficient catalysts for the allylation of aldehydes with allyl trichlorosilane [26a] or the aldol condensation of trichlorosilyl-enol ethers with aldehydes [26b]. However, the first example of supported chiral phosphorarnides on a polymeric matrix was reported only in 2005 [27]. 

Catalyst 18b, recovered by filtration and thoroughly washed with DCM, was employed in three additional runs to afford the resolved product in slightly higher ee-value at identical conversions. However, the activity of the recycled catalyst was somewhat lower than that of the fresh version, as longer reaction times were necessary to obtain the same conversions. An extension of the use of this catalyst to the kinetic resolution of other secondary alcohols was possible, although the immobihzed catalyst performed constantly less efficiently than its best nonsupported analogue [31]. 

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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. 

The first use of chiral sulfoxides as Lewis-base catalysts in the allylation of aldehydes with allyltrichlorosilane was reported in 2003. The formation of the... 

Figure 3. Chiral Lewis acid-Lewis base catalysts.

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). ... 

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. 

Intramolecular versions of the Morita-Baylis-Hillman reaction have also met with success using a dual Lewis acid/Lewis base catalyst system. Miller has shown that a combination of A-methyl imidazole (132) (10 mol%) and... 

Ionic liquids have been also explored in the Baylis-Hillman reaction [204-206]. The application of the enantiopure ionic liquid 73 in the Baylis-Hilhnan reaction by Vo-Thanh [207] resulted in an enantiomeric excess of up to 44% with 1 equiv. of the Lewis base catalyst DABCO (Scheme 81). It was shown that it was essential to have a hydroxy group incorporated in the ionic liquid in order to obtain significant ee. 

BF3 + H2O Lewis acid Lewis base catalyst cocatalyst... 

The mechanism for the addition of dialkylzincs to aldehydes has been studied. Without any activation, addition of dialkylzincs to aldehydes scarcely proceeds. Thus, how to activate dialkylzinc and/or aldehyde should be considered. There are two ways of catalyzing the addition of diorganozinc to carbonyl compounds. One is activation by Lewis base catalyst (equation 1). 

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

It has been demonstrated that the oxygen anion of initially formed product (36) effectively catalysed the [2,3]-Wittig rearrangement as a Lewis base. Other Lewis-base catalysts such as lithio or sodio 2-pyrrolidone promote the same [2,3]-Wittig rearrangement of silyl enolates generated from a-allyloxy ketones, whereas rearrangements of enolates from a-allyloxy esters were efficiently catalysed by ammonium 4-methoxybenzoate.24... 

Asymmetric aza Morita-Baylis-Hillman reactions of N-sulfonylimines or N-sulfinimines with Michael accepters in the presence a Lewis base catalyst to give the corresponding chiral a-methylene-/ -amino compounds have been described [27]. 

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. 

Strecker-type reaction of TMS cyanide with chiral sulfinimines gives diastereoselective cyanations at the imine carbon, at —78 °C in DMF, using simple metal-free Lewis base catalysts such as tetraalkylammonium carboxylates.73... 

Crossed aldol reaction between an aromatic aldehyde and the TMS enolate of another aldehyde proceeds smoothly in wet or dry DMF using a lithium carboxylate as Lewis base catalyst.158 One-pot conversion to 1,3-diols using sodium borohydride as reductant gives up to 87% yield. A similar report, using tetrabutylammonium phe-nolates as Lewis bases, is diaslereoselective.159... 

Pyridine-/V-oxidc is an efficient Lewis-base catalyst for aldol reactions of trimethyl-silyl enolate with both aryl and alkyl aldehydes in DMF at room temperature, tolerating a wide variety of sensitive substituents in the substrate.160... 

Phenoxide anions have been proved to be good Lewis base catalysts to promote syn-selective aldol reaction between TMS enolates and aldehydes.31... 

Shibasaki and co-workers disclosed a general asymmetric Strecker-type reaction that was controlled by bifunctional Lewis acid-Lewis base catalyst 14 [10], N-Fluorenylimines 15 underwent catalytic asymmetric Strecker-type reactions with binaphthol catalyst 14 to give a-aminonitriles 16 in good to excellent enantioselectivities and yields (Scheme 6). a-Aminonitrile 16 (R = Ph) could then be converted to a-aminoamide 17 in several steps. Aromatic, aliphatic, heterocyclic and a,/f-unsaturated imines 15 were used as general substrates in these reactions. The origin of the highly enantioselective cataylsis by 14 is believed to be attributed to the simultaneous activation of imines and trimethylsilyl cyanide by the... 

Scheme 6. Asymmetric Strecker synthesis with bifunctional Lewis acid-Lewis base catalyst 14 (Shibasaki and co-workers). DDQ = 2,3-dichloro-5,6-dicyano-l, 4-benzoquinone.

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. 

Tertiary amines are a type of Lewis base catalyst and are, perhaps, the most widely used catalyst. Two of the most widely used tertiary amines are... 

The active chlorine is capable, under certain conditions, of blocking reactions with Lewis base catalysts. The main effect of high chlorine content is to reduce system reactivity and crosslink density. Chlorine may also cause corrosion of delicate substrates. Chlorine content is a common test for epoxy resins in the electrical and electronic industries. 

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