Chiral scandium

Table 9.39 Chiral scandium triflate-catalyzed additions oftrimethylsilyl-substituted-allenes to aldehydes.

Table 9.40 Chiral scandium triflate-catalyzed [3+2] cycloadditions of DPS-allenes to aldehydes.

The Lewis acid-promoted reaction of aldehydes with a-substituted allylsilanes forms 3-silyltetrahydrofurans in good to high yields.169-172 The use of homochiral allylsilanes is very valuable for highly diastereo- and enantio-selective syntheses of tri- and tetrasubstituted tetrahydrofurans (Equation (43)). Catalytic asymmetric [3-1-21-cycloaddition of a-substituted allenylsilanes to aldehydes can be achieved by a chiral scandium complex.173... 

When a chiral scandium complex of 2,6-bis-(oxazolinyl)pyridine, [Sc(/f)-py-box](OTf)3, 0Tf=0S02CE3, is employed instead of Sc(OTf)3, a 2 2 chiral Jt-dimer complex of 1,4-napthosemquinone radical anion (NQ ) with Sc (R)-... 

TABLE 10. Asymmetric Michael additions catalyzed by the chiral scandium-bipyridine complex 149 (equation 41)... 

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. 

Table 3. Enantioselective Diels-Alder reactions with a chiral scandium catalyst,...

Catalytic asymmetric 1,3-dipolar cycloaddition of a nitrone with a dipolarophile has been performed using a chiral scandium catalyst [31]. The chiral catalyst, which was effective in asymmetric Diels-Alder reactions, was readily prepared from Sc(OTf)3, (7 )-(-i-)-BINOL, and d5 -l,2,6-trimethylpiperidine. The reaction of benzylbenzylide-neamine A-oxide with 3-(2-butenoyl)-l,3-oxazolidin-2-one was performed in the presence of the chiral catalyst to yield the desired isoxazolidine in 69 % ee with perfect diastereoselectivity (endolexo = > 99 1) (Sch. 8) [31,46], It was found that reverse enantioselectivity was observed when a chiral Yb catalyst, prepared from Yb(OTf)3, the same (i )-(-i-)-BINOL, and cd-l,2,6-trimethylpiperidine, was used instead of the Sc catalyst under the same reaction conditions. 

In the presence of a chiral zirconium " " or aluminum " catalyst, Bu3SnCN react with imines to give a-cyanoamines enantioselectively. The reaction of an imine and TMSCN gives the cyano amine with good enantioselectivity using a chiral scandium catalyst.Titanium catalysts have been used in the presence of a chiral Schiff base. Treatment of an imine with a chiral 1,4,6- triazabicy-clo[3.3.0]oct-4-ene and then HCN give the a-cyano amine with good enantioselectivity. 

The [3-1-2] cycloaddition of aldehydes with a-substituted allenylsilanes is a powerful means of access to dihydrofurans [450 b]. Quite recently Evans et al. reported the first example of the catalytic asymmetric version using a chiral scandium triflate complex (Scheme 10.172) [480]. 

Although the transition states of the chiral lanthanide(III)-catalyzed reactions are rather complicated due to the specific coordination number and stereochemistry of the lanthanide(III), the sense of asymmetric induction in the chiral scandium-catalyzed reactions can be rationalized by assuming an intermediate octahedral Sc(III)-dienophile complex (scheme 14). The axial chirality of (R)-binaphthol is transferred to the amine,... 

A chiral scandium catalyst prepared from Sc(OTf)3, (/ )-BINOL, and DBU is effective in enantioselective aza Diels-Alder reactions (eq 24). The reaction of iV-alkylidene- or/V-arylidene-2-hydroxyaniline with cyclopentadiene proceeds in the presence of the chiral catalyst and 2,6-di-terf-butyl-4-methylpyridine (DTBMP) to afford the corresponding 8-hydroxyquinoline derivatives in good to high yields with good to excellent diastereo selectivity and enantioselectivity. 

In the presence of the chiral scandium catalyst, the 1,3-dipolar cycloaddition of benzylbenzylideneamine A -oxide with 3-(2-butenoyl)-l,3-oxazolidin-2-one proceeds to yield the endo adduct endolexo 99/1) in 69% ee (eq 25). Chiral scandium complexes prepared from Sc(OTf)3 and 2,2 -bis(oxazolyl)-BESfOL derivatives also serve as efficient catalysts. ... 

Similarly, the catalyst prepared from jdterbium triflate (Yb(OTf)3) and Bl-NOL acts as efficient enantioselective catalyst in the reaction of the previous oxazolidine derivative and cyclopentadiene. The role of the amine addition is determined (113). The analogous chiral scandium catalysts are prepared from Sc(OTf)3, BINOL, and tertiary amine in the same manner (114). As a major difference between Yb(lll) and Sc(lll) chiral catalysts, their coordination numbers are thought although Sc(III) is known to coordinate up to seven ligands, the specific coordination of Yb(III) allows up to 12 ligands (115). 

Two reports of enantioselective Danheiser annulations have appeared in the literature. Evans et al. have reported the annulation of ethyl glyoxylate (104) to form dihydrofuran products in good to excellent enantioselectivity using a chiral scandium catalyst. For example, reaction of ethyl glyoxylate (104) with tert-butyldiphenylsilylallene 105 in the presence of the chiral scandium catalyst 106 led to dihydrofuran 107 in 91% yield and 92% ee. As... 

Perhaps the most elegant and attractive method to control absolute stereochemistry, however, is the use of asymmetric catalysis, and several examples of this approach have been applied to the Nazarov cyclization. Traimer and co-workers were the first to report a single example of a successfiil asymmetric Nazarov cyclization catalyzed by chiral scandium complex in 2003. In the exact same issue of the journal however, Aggarwal and co-workers reported a more in-depth study using copper pyBOX complexes. ... 

It worth to mention that despite the importance of the Kabachnik-Fields reaction, stereoselective versions for the synthesis of enantioenriched a-aminophosphonates are scarce [212, 213], and only few enantioselective examples have been published to date (for reviews on enantioselective catalytic direct hydrophosphonylations of imines, see Refs. [162a-c]). Organocatalytic examples use well-known chiral binol-derived phosphoric acid organocatalysts (Fig. 12.6,80 and 81) [214], and regarding metal catalysis, chiral scandium(III)-A,A -dioxide and... 

Chiral scandium-bis(oxazolinyl)pyridine (Sc-pybox) complexes catalyze various catal5dic asymmettic addition reactions with carbonyl compounds. The first report of this complex was addition and annulation reactions of allenylsi-lanes with etiiyl glyoxylate using the scandium complex. The application of these complexes was expanded to various catalytic asymmetric transformations such as aldol reactions, allylation, and ene reactions. ... 

Scheme 1 Chiral scandium-catalyzed aldol reactions...

Highly enantioselective Michael reactions of indanone and tetralone -ketoesters derivatives with a,P-unsaturated ketones promoted by a chiral scandium catalyst have been developed [123]. In the presence of Sc(OTf)3 and bipyridine (3), the reactions proceeded smoothly in dichloroethane at 40 °C to give the corresponding adducts in moderate to excellent yields with excellent enantioselectivities in most cases (Scheme 12.47). It was found that a lower concentration of the reaction mixture was key to attaining high selectivity. 

A chiral scandium complex with a new ferrocenyl-based chiral diol ligand, FER-RODIOL, was reported to be an effective catalyst for enantioselective Diels-Alder... 

It has been shown that the use of a chiral Scandium(III) catalyst in the reaction of 0 3-substituted-oxindoles with diaryliodonium salts may result in the enantioselective formation of a-arylated derivatives (76). 

Zhang, Q., Hui, Y, Zhou, X., Lin, L., Liu, X., Feng, X. (2010). Highly efficient asymmetric three-component vinylogous Mannich reaction catalyzed by a chiral scandium(III)-lV,lV -dioxide complex. Advanced Synthesis Catalysis, 352, 976-980. 

Q. Zhang, X. Xiao, L. Lin, X. liu, X. Feng, Highly enantioselective synthesis of y-substituted butenolides via the vinylogous Mukaiyama-Michael reaction catalyzed by a chiral scandium(III)-N,N -dioxide complex, Org. Biomol. Chem. 9 (2011) 5748-5754. 

SCHEME 10.25 Enantiodiveigent Friedel-Crafts alkylation catalyzed by a chiral scandium complex. 

Allenylsilanes also undergo formal [3 + 2] cycloaddition reactions with enones, aldehydes, iminium species generated in situy and acid chlorides to give a variety of five-membered products (Scheme 3-111). The reaction is considered to proceed through stepwise mechanisms. The [3 + 2] cycloaddition reaction can be performed in an enatioselective manner by using the chiral scandium catalyst. 

Scheme 3-143. Chiral scandium-catalyzed alkenylation of aldehydes using...

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