Aryl-imines, enantioselective

Table 34.2 Selected results for the enantioselective hydrogenation of N-aryl imines 1 and 2 (for structures, see Fig. 34.4) Catalytic system, reaction conditions, enantioselectivity, productivity and activity.

F. Spindler, B. Pugin, H.-P. Jalett, H.-P. Buser, U. Pittelkow, H.-U Blaser, A Technically Useful Catalyst for the Homogeneous Enantioselective Hydrogenation of N-Aryl Imines A Case Study, in Catalysis of Organic Reactions (Ed. R. E. Maltz), Dekker, New York, 1996, pp. 153-168. 

Later in 2007, Gong utilized If and saturated derivative 2 in a direct Mannich reaction between in situ generated N-aryl imines and cyclic ketones as well aromatic ketones (Scheme 5.3) [10], It was found that electron poor anilines as coupling partners gave the highest enantioselectivities. The authors postulate that acid promoted enolization of the ketone forms the reactive enol which adds to the protonated aldimine. 

Dixon reported that saturated BINOL 45 sufficiently activates various N-Boc aryl imines toward Mannich reaction with acetophenone-derived enamines to yield P-amrno aryl ketones in good yields and enantioselectivities (Scheme 5.62) [116]. The same group applied a BINOL-derived tetraol catalyst to the addition of meth-yleneaminopyrroHdine to N-Boc aryl imines. Interestingly, appendage of two extra diarymethanol groups to the BINOL scaffold resulted in a marked increase in enantiomeric excess [117]. 

While all of the aryl imine substrates examined for this Strecker methodology existed predominantly or exclusively as the E-isomers, this did not appear to be a requirement for high enantioselectivity as demonstrated in the asymmetric 42-cat-alyzed (2 mol% loading) hydrocyanation of the cyclic Z-imine 3,4-dihydroisoquino-line, which was converted to the corresponding adduct (88% yield, 91% cc) with the same sense of stereoinduction with respect to the benzylic stereogenic center as the examined acyclic E-imines (Schemes 6.41 and 6.42) [196]. 

Highly enantioselective hydrosilylation of N-aryl imines derived from aliphatic ketones was achieved by the use of (S)-ll as a chiral catalyst (Scheme 10)... 

The Zr-catalyzed asymmetric alkylation shown in Eq. (2) [8] illustrates two important principles (1) The catalytic asymmetric protocol can be readily applied to the synthesis of non-aryl imines to generate homochiral amines that cannot be prepared by any of the alternative imine or enamine hydrogenation protocols. (2) The catalytic amine synthesis involves a three-component process that includes the in situ formation of the imine substrate, followed by its asymmetric alkylation. This strategy can also be readily applied to the preparation of arylamines. The three-component enantioselective amine synthesis suggests that such a procedure maybe used to synthesize libraries of homochiral amines in a highly efficient and convenient fashion. 

Spindler, F., Pugin, B., Jalett, H.-P., Buser, H.-P., Pittelkow, U. and Blaser, H.-U. (1996) A technically useful catalyst for the homogeneous enantioselective hydrogenation of N-aryl imines A case study. Chem. Ind. (Dekker) Catal. Org. React., 68, 153. 

Ir-f-binaphane complexes show good to excellent enantioselectivities but modest TONs and low TOFs for the hydrogenation of A -aryl imines with the general structure 27 (Table 15.3).14 The reaction has to be performed in poorly coordinating solvents such as dichloromethane and at a relatively high hydrogen pressure. As with the Ir-Josiphos catalysts, the best ee s are obtained with 2,6-disubstituted /V-aryl imines (Entries 1 and 2), whereas alkyl ketimines give low enantioselectivities (Entry 3). In some cases, the addition of I2 has a beneficial effect on enantioselectivity (Entries 4 and 5). 

Significant levels of syn diastereoselectivities (5 1 to 16 1) were observed for all substrates, with the exception of an ortho-chloro-substituted aryl imine, which provided only 2 1 syn selectivity. The catalyst was viable for a variety of nitroalkanes, and afforded adducts in uniformly high enantioselectivities (92-95% ee). The sense of enantiofacial selectivity in this reaction is identical to that reported for the thiourea-catalyzed Strecker (see Scheme 6.8) and Mannich (see Tables 6.18 and 6.22) reactions, suggesting a commonality in the mode of substrate activation. The asymmetric catalysis is likely to involve hydrogen bonding between the catalyst and the imine or the nitronate, or even dual activation of both substrates. The specific role of the 4 A MS powder in providing more reproducible results remains unclear, as the use of either 3 A or 5 A MS powder was reported to have a detrimental effect on both enantioselectivities and rates of reaction. 

In 2005, Schaus and coworkers found that the natural cinchona alkaloids such as cinchonine (CN) or cinchonidine (CD) themselves can serve as highly enantioselective catalysts (10mol%) for the Mannich reaction of P-keto esters 57 with the various carbamate-protected aryl imines 58 [25]. Using either CN or CD, both enantiomers of the resulting secondary amine products 59 were obtained in excellent yields (up to 99%) and ee values (up to 96% ee) (Scheme 8.19). The extension of this protocol to encompass the use of the 2-substituted-l,3-dicarbonyl nucleophiles 60... 

Hoveyda and Snapper reported that the addition of mixed alkynylzinc reagents to various aryl imines can be catalyzed by Schiff base ligand 52 and zirconium tetraisopropoxide to afford the protected propargylamines in good yields and enantioselectivities [130]. The oxidative removal of the o anisidyl group affords the propargylamine without any racemization (Scheme 1.40). 

N Alky] and N aryl imines have received the most attention in the literature, but significant research has also been performed in the area of "activated imines, that is, imines with electron withdrawing substituents at N. In addition to having different reactivity from N alkyl and N aryl imines, these compounds are intrinsically open to further functionalization after hydrogenation. The first of these compounds to be reduced enantioselectively were the N tosyl amines. In contrast to the related reaction with N alkyl and N aryl amines, the asymmetric hydrogenations of N tosyl amines are most often catalyzed by complexes of palladium. 

The best activities were observed in methanol/toluene but the maximum tof was only 15 fr at 65 bar, r.t., fru too low for an industrial t lication. Nevertheless, these results represented a remarkable progress for the enantioselective hydrogenation of N-aryl imines. 

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