Lewis lanthanide, chiral

To achieve catalytic enantioselective aza Diels-Alder reactions, choice of metal is very important. It has been shown that lanthanide triflates are excellent catalysts for achiral aza Diels-Alder reactions [5]. Although stoichiometric amounts of Lewis acids are often required, a small amount of the triflate effectively catalyzes the reactions. On the basis of these findings chiral lanthanides were used in catalytic asymmetric aza Diels-Alder reactions. The chiral lanthanide Lewis acids were first developed to realize highly enantioselective Diels-Alder reactions of 2-oxazolidin-l-one with dienes [6]. 

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. 

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. 

Many Lewis-acid catalysts have been studied and used in the Diels-Alder reactions, ranging from the more commonly used strong Lewis acids such as AICI3, TiCU, SnCU, ZnCli, ZnBri, etc., to the milder lanthanide complexes and to the chiral catalyst. 

Catalytic asymmetric aza-Diels-Alder reactions using a chiral lanthanide Lewis acid. Enantioselective synthesis of tetrahydroquinoline derivatives using a catalytic amount of a chiral source [98]... 

Scheme 2.25 shows some examples of additions of enolate equivalents. A range of Lewis acid catalysts has been used in addition to TiCl4 and SnCl4. Entry 1 shows uses of a lanthanide catalyst. Entry 2 employs LiC104 as the catalyst. The reaction in Entry 3 includes a chiral auxiliary that controls the stereoselectivity the chiral auxiliary is released by a cyclization using (V-methylhydroxylamine. Entries 4 and 5 use the triphenylmethyl cation as a catalyst and Entries 6 and 7 use trimethylsilyl triflate and an enantioselective catalyst, respectively. 

Perhaps the most attractive method of introducing enantioselectivity into the Diels-Alder reaction is to use a chiral catalyst in the form of a Lewis acidic metal complex. In recent years, this area has shown the greatest progress, with the introduction of many excellent catalytic processes. Quite a number of ligand-metal combinations have been evaluated for their potential as chiral catalysts in Diels-Alder reactions. The most commonly used metals are boron, titanium, and aluminum. Copper, magnesium, and lanthanides have also been used in asymmetric catalytic Diels-Alder reactions. 

A more recent report by Sibi and co-workers displayed the utility of chiral lanthanide Lewis acids for addition-trapping reactions [150]. An exhaustive screening of lanthanide Lewis acids and several chiral ligands revealed that Y(OTf)3 and proline derived ligand 138 was optimal (data not shown). Upon further optimization it was discovered that achiral additives 139 and 212 increased ee s (Scheme 56, entries 2 and 3). Bulkier radicals were found to decrease the enantioselectivity (entries 4 and 5). Also, larger aryl substituents on the ligand gave similar ee s as observed for 138 (compare entries 1, 6, and 7). 

Scheme 56 Radical allylations using chiral lanthanide Lewis acids... 

The types of dienophiles which have been studied most are acrylic aldehydes, acrylates and 3-acryloyl-l,3-oxazolidines. The latter have been used predominantly in copper, magnesium, zinc and lanthanide catalyzed reactions in which the chiral Lewis acid binds in an rj2 fashion to the dienophile (complexation to both carbonyls). 

Several chiral lanthanide(III) Lewis acid catalysts, derived from chiral binaphthols, have been used in the cycloaddition reactions of cyclopentadiene with substituted iV-acryloyl-1,3-oxazolidin-2-ones. A catalyst derived from ytterbium triflate, (R)-binaphthol... 

The use of chiral lanthanide shift reagents (CLSRs) for NMR enantiomeric purity determination has become very popular (6) since the first of these compounds (54a) was reported by Whitesides and Lewis (96). Reagents 54b [Eu(hfbc)3 or Eu(hfc)3] and 54c [Eu(facam)3 or Eu(tfc)3] subsequently independently introduced by Fraser (97) and Goering (98), are most widely used, and are commercially available. 

Scheme 12) [20a]. Shibasaki et al. [20b] used a chiral in situ generated lanthanide complex (64) as catalyst. The optically active lanthanide complex 66 is postulated as the basic intermediate, activating the nitromethane as shown in 67. However, in the case of the Mukaiyama aldol addition, lanthanide Lewis acids still give moderate ee values. 

Retention of Rohrschneider-McReynolds standards of selected chiral alcohols and ketones was measured to determine the thermodynamic selectivity parameters of stationary phases containing (- -)-61 (M = Pr, Eu, Dy, Er, Yb, n = 3, R = Mef) dissolved in poly(dimethylsiloxane) . Separation of selected racemic alcohols and ketones was achieved and the determined values of thermodynamic enantioselectivity were correlated with the molecular structure of the solutes studied. The decrease of the ionic radius of lanthanides induces greater increase of complexation efficiency for the alcohols than for the ketone coordination complexes. The selectivity of the studied stationary phases follows a common trend which is rationalized in terms of opposing electronic and steric effects of the Lewis acid-base interactions between the selected alcohols, ketones and lanthanide chelates. The retention of over fifty solutes on five stationary phases containing 61 (M = Pr, Eu, Dy, Er, Yb, n = 3, R = Mef) dissolved in polydimethylsiloxane were later measured ". The initial motivation for this work was to explore the utility of a solvation parameter model proposed and developed by Abraham and coworkers for complexing stationary phases containing metal coordination centers. Linear solvation... 

Although Lewis add-catalyzed carbon-carbon bond-forming reactions are now of great interest in organic synthesis, these reactions must be conducted under strictly anhydrous conditions, because most Lewis adds react immediately with water rather than the substrates, and are decomposed or deactivated. Sc(OTf)3, however, was found to be stable in water, and effectively activated carbonyl and related compounds as a Lewis add in water. Although it had already been found that lanthanide triflates (Ln(OTf)3 Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) and yttrium triflate (Y(OTf)3) are stable in water and can act as Lewis acid catalysts in aqueous media [3], Sc(OTf)3 occasionally has even better properties even than Ln(OTf)3. Sc(OTf)3, moreover, worked well as a Lewis acid catalyst in several organic solvents, and chiral scandium triflates have also been developed. 

Although asymmetric versions of aza Diels-Alder reactions using chiral auxiliaries have been reported, only one example uses a stoichiometric amount of a chiral Lewis acid [44]. The first reported example of a catalytic enantioselective aza Diels-Alder reaction employed a chiral lanthanide catalyst [45]. A chiral ytterbium or scandium catalyst, prepared from Yb(OTf)3 or Sc(OTf)3, (i )-BINOL, and DBU, is effective in the enantioselective aza Diels-Alder reactions. The reaction of A-alkylidene- or N-arylidene-2-hydroxyaniline with cyclopentadiene proceeded in the presence of the chiral catalyst and 2,6-di-rerf-butyl-4-methylpyridine (DTBMP) to afford the corresponding 8-hydroxyquinoline derivatives in good to high yields with good to excellent diastereo- and enantioselectivity (Eq. 15). 

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