Lewis asymmetric induction

It should be noted that the sense of asymmetric induction in the lithiation/ rearrangement of aziridines 274, 276, and 279 by treatment with s-butyllithium/ (-)-sparteine is opposite to that observed for the corresponding epoxides (i.e. removal of the proton occurs at the (S)-stereocenter) [102], If one accepts the proposed model to explain the selective abstraction of the proton at the (R) -stereo-center of an epoxide (Figure 5.1), then, from the large difference in steric bulk (and Lewis basicity) between an oxygen atom and a tosyl-protected nitrogen atom, it is obvious that this model cannot be applied to the analogous aziridines. 

Effective 1,4-asymmetric induction has been observed in reactions between 2-(alkoxyethyl)-2-propenylsilanes and aldehydes. The relative configuration of the product depends on the Lewis acid used. Titanium(IV) chloride, in the presence of diethyl ether, gave 1,4-ijn-products with excellent stereoselectivity with boron trifluoride-diethyl ether complex, the amt-isomer was the major product, but the stereoselectivity was less83. 

Diallyldialkylstannanes with chiral alkyl substituents on the tin, show variable asymmetric induction in their Lewis acid catalyzed reactions with aldehydes. Using bis-(/f)-2-phenylbutyl-(di-2-propenyl)stannane, enantiomeric excesses of up to 54% were obtained via attack on the / e-face of the aldehyde96. 

High 1,2-asymmetric induction is also observed in the Lewis acid induced alkylation of an a-ethoxyearbamate with tctraalkyllcad104. 

Dienones, such as 4-[4-(trimethylsilyl)-2-butenyl]-3-vinyl-2-cyclohexenone, are useful precursors for these particular transformations the allylsilane side chain is too short for effective 1,4-addition, but just right for 1,6-addition, resulting in six-ring annulation. Three different Lewis acids can be used titanium(IV) chloride, boron trifluoride diethyl ether complex, and ethylaluminum dichloride. The best chemical yields and complete asymmetric inductions were obtained with ethylaluminum dichloride. 

Table 2. Stereoselective Annulation with 1,3-Asymmetric Induction Using Ethylaluminum Dichloride as Lewis Acid...

The most frequently encountered, and most useful, cycloaddition reactions of silyl enol ethers are Diels-Alder reactions involving silyloxybutadicncs (Chapter 18). Danishefsky (30) has reviewed his pioneering work in this area, and has extended his studies to include heterodienophiles, particularly aldehydes. Lewis acid catalysis is required in such cases, and substantial asymmetric induction can be achieved using either a chiral lanthanide catalyst or an a-chiral aldehyde. 

Asymmetric induction in the intermolecular Diels-Alder cycloaddition reactions can be achieved with chirally modified dienes and dienophiles as well as with chiral Lewis-acid catalysts [54-56]. 

Allylic silanes react with aldehydes, in the presence of Lewis acids, to give an allyl-substituted alcohol. In the case of benzylic silanes, this addition reaction has been induced with Mg(C104)2 under photochemical conditions. The addition of chiral additives leads to the alcohol with good asymmetric induction. In a related reaction, allylic silanes react with acyl halides to produce the corresponding carbonyl derivative. The reaction of phenyl chloroformate, trimethylallylsilane, and AICI3, for example, gave phenyl but-3-enoate. ... 

In spite of the modest asymmetric induction it was concluded that at least one of the chiral ligands is coordinated to the nickel in the catalyticaUy active species. An alternative interpretation was given by Wilke and coworkers [29]. They could show that (methylsalicyhdene)dimethylaluminum forms a stable adduct with nickel(O) complexes. It was concluded that the asymmetric induction in Pino s experiment might be attributed to a complex in which the chiral Hgand is complexed to the Lewis acidic aluminum. 

Asymmetric Lewis-Acid Catalyzed. Another important advance in aqueous Mukaiyama aldol reaction is the recent success of asymmetric catalysis.283 In aqueous ethanol, Kobayashi and co-workers achieved asymmetric inductions by using Cu(OTf)2/chiral >A(oxazoline) ligand,284 Pb(OTf)2/chiral crown ether,285 and Ln(OTf)3/chiral Mv-pyridino-18-crown-6 (Eq. 8.105).286... 

High levels of asymmetric induction (97-74% ee) along with high diastereoselectivity (>99 1-64 36) were reported for asymmetric 1,3-dipolar cycloaddition reactions of fused azomethine imines 315 and 3-acryloyl-2-oxazolidinone 709 leading to 711 using a chiral BINIM-Ni(n) complex 710 as a chiral Lewis acid catalyst (Equation 100) <20070L97>. 

Pentadienyltrimethylstannanes undergo regioselective conjugate additions to aldehydes, catalysed by Lewis acids. The dominant product obtained depends on the catalyst used, as shown in reaction 46. In the case of titanium tetrachloride catalysis the reaction is also stereoselective and only one diasteroisomer is obtained297. Reaction with chiral aldehydes leads to asymmetric induction with similar organotin compounds298. 

Lewis acids of chiral metal aryloxides prepared from metal reagents and optically active binaphthol derivatives have played a significant role in asymmetric synthesis and have been extensively studied.23 However, in Diels-Alder reactions, the asymmetric induction with chiral metal aryloxides is, in most cases, controlled by steric interaction between a dienophile and a chiral ligand. This kind of interaction is sometimes insufficient to provide a high level of enantioselectivity. 

Chiral dienes or chiral dienophiles or chiral Lewis acid catalysts may be involved in cycloaddition reactions. When any two of these are combined double asymmetric induction operates111. Thus the chiral diene 223 and the optically active dienophile 224 (from D-mandelic acid) gave 225 in high de values, whereas the same diene and the enantiomeric dienophile 226 (from L-mandelic acid) — a mismatched pair—formed the diastereomeric cycloadduct 227 in only 4% de (equation 121)112. 

Until recently the most popular method in asymmetric catalysis was the application of metal complexes. This is not surprising, since the use of different metals, ligands and oxidation states makes it possible to tune selectivity and perform asymmetric induction very easily. Thus, the concept of asymmetric catalysis has become almost synonymous with the use of metals coordinated by chiral ligands [1,2]. In many examples the metal is a Lewis acid [3]. 

It has been shown that metal-free Lewis acids have been applied as catalysts in a broad variety of reactions. However, in several cases the asymmetric induction in the reactions has to be improved. While many of the highly active salts are moisture sensitive, ionic liquids with the right choice of cation and anion, are quite stable. Therefore their catalytic Lewis acidic activity is weak. The research field presented still has much room for improvanent and further investigations and results are continuously reported in the literature in an uiCTeasing number due to the large potential of metal-free Lewis acids. 

In 2006, Xu and Xia et al. revealed the catalytic activity of commercially available D-camphorsulfonic acid (CS A) in the enantioselective Michael-type Friedel-Crafts addition of indoles 29 to chalcones 180 attaining moderate enantiomeric excess (75-96%, 0-37% ee) for the corresponding p-indolyl ketones 181 (Scheme 76) [95], This constitutes the first report on the stereoselectivity of o-CSA-mediated transformations. In the course of their studies, the authors discovered a synergistic effect between the ionic liquid BmimBr (l-butyl-3-methyl-l/f-imidazohum bromide) and d-CSA. For a range of indoles 29 and chalcone derivatives 180, the preformed BmimBr-CSA complex (24 mol%) gave improved asymmetric induction compared to d-CSA (5 mol%) alone, along with similar or slightly better yields of P-indolyl ketones 181 (74-96%, 13-58% ee). The authors attribute the beneficial effect of the BmimBr-D-CSA combination to the catalytic Lewis acid activation of Brpnsted acids (LBA). Notably, the direct addition of BmimBr to the reaction mixture of indole, chalcone, d-CSA in acetonitrile did not influence the catalytic efficiency. 

The lactone concept is not restricted to the simple model biaryl synthesis presented here. It has been successfully expanded to a broad series of structurally diverse biaryl substrates (e.g., lactones with additional stereocenters and functional groups, configurationally stable lactones, seven-membered lactones, and again configurationally unstable biaryl hydroxy aldehydes ), to different activation modes in the ring-opening step (e.g., use of metallated nucleophiles, carbonyl activation by Lewis acids, (Ti -complexation, etc.), and for various strategies of stereoselection (e.g., external vs. internal asymmetric induction). ... 

Then the potential for asymmetric induction of some of these chiral ionic liquids was investigated. The aza Diels-Alder cycloaddition between the enantiomericaUy pure (/ )-imine 31 and the Danishefsky s diene 32 was chosen as model asymmetric reaction (Scheme 8). The reaction was performed at room temperature for 5 h using 0.5 equiv. of ionic liquid and 1.5 equiv. of diene. In the absence of chiral ILs, the same coupling required a Lewis acid catalyst (0.1 equiv. of ZnC ) and afforded the main product 33 in 60% yield and low diastereoselectivity (32% de). 

Jurczak and Kiegiel reported that additions of allylmagnesium chloride and allyl bromide in the presence of Zn to iV-methyl and W-phenylglyoxyloyl-(2R)-borane-10,2-sultam occurred in a diastereoselective manner. Similarly, the Lewis acid mediated addition of allyltrimethylsilane also gave good diastereoselectivity and in the case with TiCU a change of direction of asymmetric induction was observed <99TL1009>. 

An alternative approach in the asymmetric catalysis in 1,3-dipole cycloaddition has been developed by Suga and coworkers. The achiral 1,3-dipole 106 was generated by intramolecular reaction of an Rh(ii) carbene complex with an ester carbonyl oxygen in the Rh2(OAc)4-catalyzed diazo decomposition of <9-methoxycarbonyl-o -diazoacetophenone 105 (Scheme 12). The asymmetric induction in the subsequent cycloaddition to G=G and G=N bond was achieved by chiral Lewis acid Sc(iii)-Pybox-/-Pr or Yb(iii)-Pybox-Ph, which can activate the dipolarophile through complexation. With this approach, up to 95% ee for G=0 bond addition and 96% ee for G=G bond addition have been obtained, respectively. ... 

Certain olefinic substrates undergo thermally-forbidden [2 + 2] type cycloaddition in the presence of Lewis acid catalysts through coordination to the acceptor molecules. Scheme 111 illustrates the enantiose-lective version of this reaction (271). Some thio acetylenes can also be used. Substantial asymmetric induction has been observed in cycloadditions of styrenes and 1,4-benzoquinones using a stoichiometric amount of a chiral Ti(IV) complex (272). The [2 + 2] cycloadducts are readily rearranged to 2-ary 1-2,3-dihydrobenzofirrans. 

The first report of an asymmetric Diels-Alder reaction with chiral Lewis acids (252) was made by Russian chemists in 1976 (253). Koga was probably the first to report a meaningful enantioselective Diels-Alder reaction (Scheme 105) in which the cyclopentadiene-methacro-lein exo adduct was obtained in 72% ee with the aid of 15 mol % of a menthol-modified aluminum chloride (254). The ee is highly dependent on the structures of the substrates, and asymmetric induction has not been observed with methyl acrylate as dienophile. Disproportionation... 

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