Asymmetric reactions imines

Keywords aza-Diels-Alder reactions, imines, aidimines, chirai Lewis acids, asymmetric synthesis... 

The Staudinger reaction [92], a [2 + 2]-cycloaddition of a ketene and a nucleophilic imine, usually proceeds by an initial imine attack on the ketene thus forming a zwitterionic enolate which subsequently cyclizes. This reaction is an expedient route to p-lactams, the core of numerous antibiotics (e.g., penicillins) and other biologically active molecules [93]. In contrast, for Lewis-base catalyzed asymmetric reactions, nonnucleophilic imines are required (to suppress a noncatalyzed background reaction), bearing, for example, an N-Ts [94] or -Boc-substituent [95]. 

In asymmetric reactions, chiral phosphine ligands such as BINAP derivatives are used as effective chiral ligands in silver complexes. In particular, an Agr-BINAP complex activates aldehydes and imines effectively and asymmetric allylations,220-222 aldol reactions 223 and Mannich-type reactions224 proceed in high yield with high selectivity (Scheme 51). 

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... 

It has been reported that the hydrogenation of imine ArC(Me)=NCH2Ph proceeds with enantioselectivity of up to 96% when Rh(I)-sulfonated BDPP is used in a two-phase system. However, the asymmetric reaction of ON bonds with ruthenium(II) catalyst is rather rare.99 Willoughby and Buchwald100 demonstrated a titanocene catalyst that shows good to excellent enantioselectivity in the hydrogenation of imine. 

The optically active catalyst 93, formed from triphenyl borate and (R)-binaphthol, catalyzes the asymmetric reaction of the dienes 94 (R1 = H or Me) with the imines 95 (R2 = Ph, 3-pyridyl or cyclohexyl). The products 96 are formed in greater than 80% ee (equation 56). Treatment of the diene 94 (R1 = H) (Danishefsky s diene) with the chiral imine 97 leads to the diastereomers 98 and 99 in the ratio 99 1 (equation 57)50. 

The asymmetric reactions discussed in this chapter may be divided into three different types of reaction, as (1) hydrometallation of olefins followed by the C—C bond formation, (2) two C C bond formations on a formally divalent carbon atom, and (3) nucleophilic addition of cyanide or isocyanide anion to a carbonyl or its analogs (Scheme 4.1). For reaction type 1, here described are hydrocarbonyla-tion represented by hydroformylation and hydrocyanation. As for type 2, Pauson-Khand reaction and olefin/CO copolymerization are mentioned. Several nucleophilic additions to aldehydes and imines (or iminiums) are described as type 3. 

Novel asymmetric conjugate-type reactions have been accomplished with Cinchona alkaloid-derived chiral thioureas, including less traditional reactions such as asymmetric decarboxylation [71]. In the following discussion, asymmetric reactions involving nitro-olefms, aldehydes and enones, and imines will be highlighted (Fig. 5). 

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). 

Asymmetric reactions of homologated organozlncs with aldehydes and imines... 

Reactions with imines also occur under similar conditions leading to the formation of difluorinated /1-lactams [196,197]. Formally, this reaction corresponds to a [2+ 2]-cycloaddition across an imine there is also an isolated report of a difluoroketene reaction, shown in Eq. (63) [198]. Useful chemistry of a silyl difluoroketene acetal was reported recently Eq. (64) shows the efficient asymmetric reaction between this reactive carbon nucleophile and aldehydes catalysed by chiral Lewis acids [199]. 

Although asymmetric reactions using chiral Lewis acids are of great current interest as one of the most efficient methods for the preparation of chiral compounds, examples using imines as electrophiles are rare compared to those us-... 

The chiral boron complex prepared in situ from chiral binaphthol and B(OPh)3 is utilized for the asymmetric aza-Diels-Alder reaction of Danishefsky s diene and imines [67] (Eq. 8A.43). Although the asymmetric reaction of prochiral imine affords products with up to 90% ee, the double asymmetric induction with chiral imine by using oc-benzylamine as a chiral auxiliary has achieved almost complete diastereoselectivity for both aliphatic and aromatic aldimines. This method has been successfully applied to the efficient asymmetric synthesis of anabasine and coniine of piperidine alkaloides. 

Stoichiometric and catalytic asymmetric reactions of lithium enolate esters with imines have been developed using an external chiral ether ligand that links the components to form a ternary complex.36 The method affords /i-lactams in high enantiomeric excess. 

The required chiral sulfur ylide of type 59 is formed in a reaction with a diazo compound in the presence of an achiral metal catalyst. Subsequently, asymmetric reaction of the chiral ylide 59 with the C=N double bond of the imine proceeds diastereoselectively and enantioselectively, giving the optically active aziridine 57. The chiral sulfide catalyst released is then used for the next catalytic cycle. The cat-alytically active species in the asymmetric process is the sulfide, so this concept can also be regarded as an organocatalytic reaction. 

This reaction involving asymmetrically substituted imines and carbonyl O-oxides occurs with a high degree of stereoselectivity and only 3,4,5-trisubstituted dioxazolidines 16a-g were obtained as a mixture of as- and trans-isomers with predominance of fir-isomers. The structure and ratio of isomers were established by NMR spectroscopy <1995J (P1)41>. 

The second part of the chapter deals with several kinds of asymmetric reactions catalyzed by unique heterobimetallic complexes. These reagents are lanthanoid-alkali metal hybrids which form BINOL derivative complexes (LnMB, where Ln = lanthanoid, M = alkali metal, and B = BINOL derivative). These complexes efficiently promote asymmetric aldol-type reactions as well as asymmetric hydrophosphonylations of aldehydes (catalyzed by LnLB, where L = lithium), asymmetric Michael reactions (catalyzed by LnSB, where S = sodium), and asymmetric hydrophosphonylations of imines (catalyzed by LnPB, where P = potassium) to give the corresponding desired products in up to 98% ee. Spectroscopic analysis and computer simulations of these asymmetric reactions have revealed the synergistic cooperation of the two different metals in the complexes. These complexes are believed to function as both Brpnsted bases and as Lewis acids may prove to be applicable to a variety of new asymmetric catalytic reactions.1,2... 

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