Catalytic Asymmetric Allylation of Imines

The first step of the catalytic cycle reaction is presumably an initial tin to palladium transmetallation to generate an t allylpalladium species that adds on the imine. The catalyst is then regenerated following a second N Pd to N Sn transmetallation. 

Cook reported that a 3,3 bis(trifluoromethyl) BINOL catalyzed asymmetric addition of allylindium to hydrazones proceeds in modest to good enantioselec tivities (10 92% ee) [90]. The stoichiometric version of this reaction yields much higher enantioselectivities (84 97% ee). Jacobsen later found that a chiral urea catalyst is effective in catalyzing a similar transformation [96]. The bifunctional catalyst 55 bearing a hydrogen bond donor and a Lewis base that are properly 

The last class of allylation reactions that are amenable to asymmetric catalysis employs allylboronate derivatives. Schaus reported that several chiral BINOL deri vatives catalyze the enantioselective asymmetric allylboration of acyl imines [97]. This reaction is most effective when 3,3 diphenyl BINOL acts as the catalyst and allyldii sopropoxyborane is the nucleophile. The allylation products are obtained in good yields (75 94%) and excellent enantiomeric excesses ( 90% ee) for both aromatic and aliphatic imines (Table 1.13). 

Several catalytic asymmetric allylation reactions have been developed specifically for iminoester derivatives, but the level of enantioselection remains typically only in the lowto high 80s (Table 1.15). Allylstannanes [99], allylsilanes [100], allyltrimethox ysilanes [101], and allylboronates [102] are suitable nucleophiles in these copper or zinc catalyzed processes. 

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More recently, catalytic asymmetric allylations of imines and imine derivatives in aqueous media have been studied. An /V-spiro C2-symmetrical chiral quaternary ammonium salt (5,5)-I-Br (,S, .S )-()-Np-NAS-Br] has been evaluated in the allylation of glycine tert-Bu ester benzophenone Schiff base [Ph2C=NCH2COOCMe3] for synthesis of both natural and unnatural a-amino acids (Eq. 11,45).76... 

The first catalytic asymmetric allylation of imines has been reported using allyltri- -butyltin in the presence of a chiral 7r-allylpalladium complex.179 Zirconium is also demonstrated as a metal center for the design of chiral Lewis acid catalysts that are suitable for the activation of bidentate imino compounds.180 Jprgensen reports high enantio-selective allylation of ct-imino esters (Equation (52)).181... 

Scheme 5.2.87 Catalytic asymmetric allylation of imine 389 via BlNAP-derived catalyst...

Synthesis of homoallylamines by catalytic asymmetric allylation of imines with allyl silanes using a chiral bis x-allyl palladium complex, also using allylstannanes (see 1st edition). 

Catalytic asymmetric allylation of imines 8 with allyltributylstannane 3a is achieved by the use of the chiral 7i-allylpalladium complex 20a as a catalyst (Eq. 6) [6]. The reaction of imine 8g with 1.25 equivalents of allyltributylstannane 3a in the presence of 5 mol% of 20a and 1 equivalent of water in THE gives 9g in 76% yield with 90% ee. Repeated recrystallization of the chiral catalyst 20a is important to obtain high enantioselectivity, since the reaction employing the... 

SCHEME 17.23. Catalytic asymmetric allylation of imines via a Claisen rearrangement. 

However, it could be shown that in principle simple imines can be used successfully as well for asymmetric aminoalkylation reactions catalyzed by chiral Lewis acids. The asymmetric allylation of simple imines 16 with allyltributylstannane (Scheme 6) catalyzed by the / -pinene derivative 17 [32a], for example furnished comparatively good results (for related asymmetric catalytic allylations of simple imines, see [32b-d]). Moreover, it was demonstrated on the basis of several Strecker-type syntheses [33-35] that catalysts such as the chiral aluminum complex 18 (Scheme 6) [33a—b] are also well suited for enantioselective aminoalkylations with simple imines. The mechanism indicated in Scheme 6 shows that the... 

The allylation of a-iV-tosylimino esters, highly activated imines, proceeds by catalytic use of a Lewis acid. Tol-BINAP-Cu(l) complexes are effective catalysts of asymmetric allylation of these imines with allylsilanes (Equation (28)).124 125 The presence of an aryl group at the position j3 to silicon improves the enantioselectivity. 

I 4 C-C, C-O, and C-B Bond Formation by Pincer Complexes Including Asymmetric Catalysis Table 4.2 Catalytic allylation of imines with allyl cyanides. 

Nitrones have a more reactive C=N bond toward nucleophilic addition compared to imines. In spite of this fact, there have been only a limited number of studies on the nucleophilic addition reactions of nitrones, particularly organometallic reagents.352-355 During the last decade, research related to reactions of nitrones with zinc-containing reagents was essentially focused on (i) dialkylzinc-assisted alkynylations356-358 and vinylations359 of nitrones, (ii) catalytic asymmetric nucleophilic additions to the C=N bond,360-364 and (iii) nitrone allylations by allylzinc halides.365,366... 

For benzoic acid acceleration in Yb(OTf)3-catalyzed allylation of aldehydes in acetonitrile, (a) As-pinall, H.C. Greeves, N. Mclver, E. G. Tetrahedron Lett. 1998, 39, 9283. For acetic acid acceleration in Yb(fod)3-catalyzed ene reaction of aldehydes with alkyl vinyl ethers, ene reaction of aldehydes with alkyl vinyl ethers, (b) Deaton, M. V. Ciufolini, M.A. Tetrahedron Lett. 1993, 34, 2409. Yamamoto et al. reported Brpnsted acid-assisted chiral Lewis acids and Lewis acid-assisted Brpnsted acids which were used for catalytic asymmetric Diels-Alder reactions and protonations and stoichiometric asymmetric aza Diels-Alder reactions, aldol-type reactions of imines, and an aldol reaction, (c) Ishihara, K. Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 1561. (d) Ishihara, K. Kurihara, H. Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 3049. (e) Ishihara, K. Nakamura, S. Kaneeda, M. Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 12854. (f) Ishihara, K. Miyata, M. Hattori, K. Tada, T. Yamamoto, H. J. Am. Chem. Sc c. 1994, 116, 10520. (g) Yamamoto, H. J. Am. Chem. Soc 1994, 116, 10520. (h) ishihara, K. Kurihara, H. Matsumoto, M. Yamamoto Ishihara, K. Kurihara, H. Matsumoto, M. Yamamoto, H. J. Am. Chem. Soc 1998, 120, 6920. 

Highly activated imines such as u-N-losylimirio esters can be catalytically allylated wifh a Lewis acid. j0rgensen [420] and Lectka [227 b] have reported the Lewis acid-catalyzed enantioselective allylation of an a-imino ester wifh allylsilanes (Scheme 10.148). Tol-BINAP-Cu(I) complex is effective in this asymmetric process as well as the Mannich-type reaction wifh silyl enolates. Aromatic substituents on fhe allyl group dramatically improve fhe enantioselectivity. 

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

Catalytic Asymmetric Nucleophilic Addition to Achiral Imines 27 Table 1.12 Allylation of hydrazones. 

Compared with well-established electrophilic it-allylpalladium chemisty, the catalytic asymmetric reaction via umpolung of jt-allylpalladium has received very limited exploration [93]. Zhou and co-workers investigated the Pd-catalyzed asymmetric umpolung allylation reactions of aldehydes [22a, 94], activated ketones [95], and imines [96] by using chiral spiro ligands (5)-18e, (S)-17c, and (5)-17a, respectively. One representative example is that of the Pd/(5)-18e-catalyzed umpolung allylation of aldehydes with allylic alcohols and their derivatives, which provided synthetically useful homoallylic alcohols from readily available allylic alcohols, with high yields and excellent enantioselectivities (Scheme 33). 

SCHEME 7.10 Catalytic asymmetric 1,3-dipolar cycloadditions of JV.iV -cyclized azomethine imines to allyl alcohol. 

Another example of a catalytic asymmetric [3,31-sigma-tropic rearrangement is the catalytic asymmetric amino allylation of aldehydes developed by Rueping and Anton-chick and recently explored by Ren and Wulff (see Scheme 17.23). In this reaction, the homoallyhc amine 96 first condenses with the aldehyde 97 giving imine 98. With the help of an acid catalyst, the i minium ion of imine 98 is formed and the cationic aza-Cope reaction can then ensue giving protected homoallylic amine 99. After treatment... 

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