Imines asymmetric additions

Reactions of chiral allylic boranes with carbonyl compounds Reactions of chiral allyl boranes with imines Asymmetric Addition of Carbon Nucleophiles to Ketones Addition of alkyl lithiums to ketones Asymmetric epoxidation with chiral sulfur ylids Asymmetric Nucleophilic Attack by Chiral Alcohols Deracemisation of arylpropionic acids Deracemisation of a-halo acids Asymmetric Conjugate Addition of Nitrogen Nucleophiles An asymmetric synthesis of thienamycin Asymmetric Protonation... 

Tanner et al. also used an aziridine carbinol (viz. 54) as chiral ligand in asymmetric addition of diethylzinc to hT-(diphenylphosphinoyl)imines (Scheme 41) [54]. 

There are many reports on the asymmetric addition of nucleophiles to carbon-nitrogen double bonds [6]. However, the majority of these reports are based on substrate control and rely on chiral auxiliaries in imines. Moreover, almost all of these reports are just for aldo-imine cases [7]. 

Regarding the reagent control asymmetric addition to imines, there were three reports with aldo-imines. Based on our best knowledge, no asymmetric addition to ketimine was reported prior to our work (vide infra). 

Asymmetric addition to ketimine in a reagent controlled manner has seldom been reported, even by 2008. When we investigated the potential for tbis asymmetric addition around 1992, there were no known examples. In 1990, Tomioka et al., reported the first asymmetric addition of alkyl lithium to N-p-methoxyphenyl aldo-imines in the presence ofa chiral (3-amino ether with 40-64% ee [8] (Scheme 1.11). In 1992, Katritzky reported the asymmetric addition of Et2Zn to in situ prepared N-acyl imine in the presence of a chiral (3-amino alcohol with 21-70% ee [15] (Scheme 1.12). In the same year, Soai et al., reported the asymmetric addition of dialkylzinc to diphenylphosphinoyl imines in the presence of chiral (3-amino alcohols with 85-87% ee [16] (Scheme 1.13). These three reports were, to the best of... 

Hoppe, I., Schollkopf, U., Nieger, M., and Egert, E., Asymmetric addition of a chiral cyclic phosphite to a cyclic imine — synthesis of phosphonic acid analogues of d- and L-penicillamine, Angew. Chem., Int. Ed. Engl., 24, 1067, 1985. 

Yamakoshi, K., Harwood, S.J., Kanai, M., and Shibasaki, M., Catalytic asymmetric addition of diphenylphosphine oxide to cyclic imines, Tetrahedron Lett., 40, 2565, 1999. 

In the presence of ZrCU or HC1, cyclization of y - a I k o x y a 11 y I s t a n n a n e 158 bearing (i )-(+)-l-phenylethylamine as a chiral auxiliary occurs to produce trans-fi-aminocyclic ether 159 with high de (91%). As shown in Scheme 3-55, asymmetric addition of an allyl group to the imine carbon can be explained by the modified Cram model 160. The attack of the allylic y-carbon approaches... 

Hagiwara et al.107 reported the chiral Pd(II) complex-catalyzed asymmetric addition of enol silyl ethers to imines, based on the belief that Pd(II) enolate was involved in the reaction. They found that with compound 171a as the catalyst, very low enantioselectivity was obtained in the asymmetric reactions between silyl enol ether and imine compounds (Scheme 3-58). However, in the... 

Scheme 6.24. Representative asymmetric additions of cyanide to imines promoted by non-Zr catalysts.

Sect. 3.2). However, this approach is limited to the few trialkylboranes that are easily available and cheap since only one of the three alkyl group is transferred. By using a triethylborane as a chain transfer reagent, the reaction could be extended to alkyl iodides as radical precursors. Bertrand [94,114] and Naito [95,97] reported both the use of triethylborane for the tin-free addition of alkyl iodides to imines. A typical example for a tentative of asymmetric addition to a glyoxylate imine is depicted in Scheme 50 (Eq. 50a). More recently additions to isatin imines were reported (Eq. 50b) as well as addition to 2H-aziridine-3-carboxylates by Lemos [100] and Somfai [101] (Eq. 50c). 

ASYMMETRIC ADDITION OF CYANIDE AND ISOCYANIDE TO ALDEHYDES OR IMINES... 

CuOTf/PyBox System The first direct asymmetric addition of alkynes to imines, generated from aldehydes and amines in situ, was reported by using copper salts in the presence of chiral PyBox ligand (Scheme 5.2). The products were obtained in good yields and excellent enantioselectivities in most cases. When toluene was used as solvent, up to 93% yield and 99% ee were obtained. Up to 99.5% ee was obtained when the reaction was carried out in 1,2-dichloroethane. The reaction can also be performed in water smoothly, and good enantioselectivities (78-91% ee) were obtained. 

Scheme 5.2. Asymmetric addition of alkynes to imines generated from aldehydes and amines.

Ricci et al. [85] reported the use of a quinidine-derived chiral catalyst in the asymmetric addition of nitromethane to iV-Boc imine 40. At around the same time, S chans and co-workers used a dihydroquinidine-derive chiral thiourea DHQD-134 applicable to nitromethane and nitroethane 149 [86]. The application of nitroethane conveniently generates a tertiary stereogenic center in the P-nitroamine product 151. The methodology presented by Schaus is also applicable to novel... 

At around the same time, other groups further reported the deprotonation-activation of malonates for the asymmetric addition to imines. Various malonates and aromatic V-acyl imines produced high yielding adducts with excellent stereoselectivities [87, 88]. 

In 2008, the same group employed chiral dicarboxylic acid (R)-5 (5 mol%, R = 4- Bu-2,6-Me2-CgHj) as the catalyst in the asymmetric addition of aldehyde N,N-dialkylhydrazones 81 to aromatic iV-Boc-imines 11 in the presence of 4 A molecular sieves to provide a-amino hydrazones 176, valuable precursors of a-amino ketones, in good yields with excellent enantioselectivities (35-89%, 84-99% ee) (Scheme 74) [93], Aldehyde hydrazones are known as a class of acyl anion equivalents due to their aza-enamine structure. Their application in the field of asymmetric catalysis has been limited to the use of formaldehyde hydrazones (Scheme 30). Remarkably, the dicarboxylic acid-catalyzed method applied not only to formaldehyde hydrazone 81a (R = H) but also allowed for the use of various aryl-aldehyde hydrazones 81b (R = Ar) under shghtly modified conditions. Prior to this... 

Chiral phosphoric acids powerful organocatalysts for asymmetric addition reactions to imines (S. J. Connon, 2006) [5a]. 

Carbon-Carbon Bond-Forming Reactions TABLE 9.32. ASYMMETRIC ADDITION TO IMINES"... 

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