Enantioselectivity addition reactions

The first reports on enantioselective addition reactions of achiral organometallic reagents, modified by aprotic chiral additives, described the addition of Grignard reagents to prostereogenic carbonyl compounds in the presence of ( + )-(/ ,/J)-2,3-dimethoxybutane (l)4 5, (-)-tetrahydro-2-methylfuran (2)6, (-)-l-[(tetrahydro-2-furanyl)methyl]pyrrolidine (3)7 or (-)-sparteine (4)8. The enantioselectivity, however, was poor (0-22% ee). 

Enantioselective Addition Reactions of Allylic Stannanes. There have been several studies of the enantiomers of a-oxygenated alkenyl stannanes. The chirality of the a-carbon exerts powerful control on enantioselectivity with the preference for the stannyl group to be anti to the forming bond. This is presumably related to the stereoelectronic effect that facilitates the transfer of electron density from the tin to the forming double bond.182... 

In this case the absolute configuration at (at least) one of the chiral units needs to be determined. This situation is encountered, for example, in enantioselective addition reactions of olefins with known configuration when two stereogenic centers are created and the olefin geometry is translated to the product in a predictable way. For example, the enantioselective vicinal hydroxylation of (ZT)-l,2-disubstituted olefins97 98, such as tert-butyl (ZT)-3-(methoxycar-bonyl)-2-propenylcarbamate (for assignment, see p 439). 

On the other hand, approaches to the use of catalytic amounts of chiral ligands have been developed. Thus, the use of a sub-stoichiometric amount (50 mol%) of DBNE (1) affords A,A-diphenylphosphinylamine with 85% in 69% yield121a. Similarly, 25 mol% of chiral aziridinyl alcohol 56 (R = - ) affords (V,(V-diphenylphosphinylamine with 65% in 60% yield123. In the enantioselective addition reaction of diethylzinc to a nitrone, 20 mol% of the metal alkoxide of diisopropyl tartrate 62 catalyzed the formation of a... 

Bernadi and Scolastico, and later Evans in a more effective manner, indicated that the enantioselective addition reaction using silyl enol ethers can be catalyzed by Lewis acidic copper(II) cation complexes derived from bisoxazolines [38-40]. In the presence of the copper complex (S,S)-14 (10 mol %), silyl enol ethers derived from thioesters add to alkylidenemalonates or 2-alkenoyloxazo-lidone in high ees (Scheme 12). Bernadi, Scolastico, and Seebach employed a titanium complex derived from TADDOL for the addition of silyl enol ethers to nitroalkenes or 2-cyclopentenone [41-43], although these are stoichiometric reactions. 

Catalysis with Pt(Il) Complexes. Fujimura has recently reported the enantioselective addition reaction of isobutyrate-derived dimethyl substituted silyl ketene acetal 125 to aldehydes (Eq. 8B2.29 and Table 8B2.15) [35]. The process utilizes a novel Pt(II) complex first reported by Pregrosin and has several salient features. In this regard, the complex is readily assembled and... 

Catalytic enantioselective addition reactions of alkyllithium or -zinc reagents to preformed imines have been described [34, 35]. Hoveyda, Snapper, and co-workers have described a direct three-component variant of this reaction [36]. Accordingly, several chiral, non-racemic aromatic as well as aliphatic amines were synthesized by the reaction of the corresponding aldehydes, o-anisidine 132, and alkylzincs using a Zr catalyst with a chiral peptide ligand 133 (Scheme 9.24). 

Enantiomeric purity, palladacycle applications, 8, 295 Enantioselective addition reactions, nucleophiles to allylic... 

K. Soai, Rational Design of Chiral Catalysis for the Enantioselective Addition Reaction of Dialkylzincs Enantiomer 1999, 4, 591-598. 

Jorgensen et al. reported that C2-symmetric bis(oxazoline)-copper(II) complex 25 also acts as chiral Lewis acid catalyst for a reaction of allylic stannane with ethyl glyoxylate [37]. Meanwhile, p-Tol-BINAP-CuCl complex 26 was shown to be a promising chiral catalyst for a catalytic enantioselective allylation of ketones with allyltrimethoxysilane under the influence of the TBAT catalyst [38]. Evans and coworkers have developed (S,S)-Ph-pybox-Sc(OTf)3 complex 27 as a new chiral Lewis acid catalyst and shown that this scandium catalyst promotes enantioselective addition reactions of allenyltrimethylsilanes to ethyl glyoxylate [39]. But, when the silicon substituents become bulkier, nonracemic dihydrofurans are predominantly obtained as products of [3+2] cycloaddition. 

Recently, copper-catalyzed enantioselective addition reactions in the presence of phosphorus amidite 258 have also been applied to different Michael acceptors. Thus, both symmetrical and unsymmetrical 4,4-disubstituted cyclohexa-2,5-dienones 261 were found to add diethylzinc with moderate to high enantioselectivities and good... 

In 1995, Soai and coworkers reported a highly enantiose-lective asymmetric autocatalysis of pyrimidyl alkanol in the enantioselective addition reaction of I-Pr2Zn to pyrimidine-5-carboxaldehyde (equation 63). When a 5-pyrimidyl alkanol with a small enantiomeric excess such as 5x10 % is added to j-Pr2Zn and pyrimidine-5-carboxaldehyde, then the reaction... 

Other organometallic compounds, including aUylic stannanes, allylic samarium, allylic germanium, and allylic indium compounds add to aldi-mines in the same manner. Aryltrialkylstannanes also add the aryl group to Al-tosyl imines using a rhodium catalyst and sonication. Catalytic enantioselective addition reactions are well known, including reactions in an ionic liquid.Allylic... 

Taddei and cowoikers reported that chiral allyltrimethylsUanes containing an optically active ligand derived from (-)-myrtenal attached to silicon (96) underwent enantioselective addition reactions with achiral aldehy s ( heme 46) to give, after acid hydrolysis, optically active homoallyl alcohols (98). A variety of Lewis acids were exanuned to optimize enantiomeric excess, and TiCU was found to be the most effective catalyst. The results of the TlCU-promoted additions are reported in Table 12. ... 

Lewis Basic Phosphoramides. In a series of elegant investigations, Denmark has documented an aldol process that utilizes trichlorosilyl enolates such as 101 and 105 in catalytic, enantioselective addition reactions (Eqs. (8.28) and (8.29)) [45]. These unusual enoxysilanes are prepared by treatment of the corresponding tribu-tylstannyl enolates with SiCl4. Trichlorosilyl enolates are sufficiently reactive to add to aldehydes at -78 °C, but their addition can be substantially accelerated by the addition of Lewis basic phosphoramides. The use of catalytic amounts of chiral phosphoramides leads to the formation of optically active products. Thus, treatment of the cyclohexanone or propiophenone-derived trichloroenolsilanes 101 and 105 with a variety of aldehydes afforded adducts displaying high levels of simple diastereoselectivity and up to 96% ee. On the basis of the stereochemical outcome of the reaction, Denmark has postulated that the reaction proceeds through an or-... 

Scheme 7.20 Enantioselective addition reactions to glyoxylic oxime ether.

Antilla and coworkers further extended their methodology to the addition of an oxygen nucleophile, instead of a nitrogen nucleophile (see Scheme 3.54), to imines (Scheme 3.56) [115]. They successfully developed the catalytic enantioselective addition reaction of alcohols as oxygen nucleophiles with N benzoyl imines using chiral phosphoric acid Ig. The method provides straightforward access to chiral hemiaminal ethers with high enantioselectivities. 

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