Chiral imine

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Darzens reactions between the chiral imine 52 and a-halo enolates 53 for the preparation of nonracemic aziridine-2-carboxylic esters 54 (Scheme 3.17) were studied by Fujisawa and co-workers [61], It is interesting to note that the lithium enolate afforded (2K,3S)-aziridirie (2i ,3S)-54 as the sole product, whereas the zinc enolate give rise to the isomer (2S,3i )-54. The a-halogen did not seem to affect the stereoselectivity. 

Chiral imines derived from 1-phenylethanone and (I. Sj-exo-l, 7,7-trimethyIbicyclo-[2.2.1]heptan-2-amine [(S)-isobornylamine], (.S>1-phenylethanamine or (R)-l-(1-naphthyl) ethanamine are transformed into the corresponding (vinylamino)dichloroboranes (e.g., 3) by treatment with trichloroborane and triethylamine in dichloromethane. Reaction of the chiral boron azaenolates with aromatic aldehydes at 25 "C, and subsequent acidic hydrolysis, furnishes aldol adducts with enantiomeric excesses in the range of 2.5 to 47.7%. Significantly lower asymmetric inductions are obtained from additions of the corresponding lithium and magnesium azaenolates. Best results arc achieved using (.S )-isobornylamine as the chiral auxiliary 3. 

In contrast to ordinary chiral aldehydes (having no ability to be chelated), the reaction of 9-allyl-9-borabicyclo[3.3.1]nonane(allyl-9-BBN) with the corresponding chiral imines 4 produces the isomer syn-6 either exclusively or predominantly (Cram selectivity Table 8)5,6. The very high 1,2-asymmetric induction is explained by a six-membered. chair-like transition state, in which the inline R group occupies an axial position due to the stereoelectronic effect of imines (R CH = NR). 

A modified Cram model 7 and/or Felkin model 8 is proposed for the 1.2-asymmetric induction on chiral imines. 

The reaction of allyl-9-BBN with the chiral imine 1 gives the Cram isomer 2 predominantly5,6. The 1,3-asymmetric induction is developed by a transition state 3, in which the 1,2-axial-equa-torial interaction between R and the ligand (L) plays an important role in the high chiral induction. 

An interesting example from carbohydrate chemistry is the boron trifluoride-diethyl ether complex catalyzed nucleophilic addition of silyl enol ethers to chiral imines (from n-glyceralde-hyde or D-serinal)22. This reaction yields unsaturated y-butyrolactones with predominantly the D-arabino configuration (and almost complete Cram-type erythro selectivity). 

Mainly sulfoxide groups are introduced as chiral auxiliaries for the modification of a,/J-unsat-urated enones (see Section D.1.5.3.5.). Chiral imine derivatives have also been used (see Section D.1.5.3.1.). Various chiral alcohols, and in particular 8-phenylmenthol, have been successfully used as auxiliaries, mainly in two-fold Michael additions to a,/ -unsaturatcd esters. 

Furthermore, intramolecular cyclization of acyclic chiral imines, in which the imine and the enone groups are separated by alkyl chains, yield optically active cyclohexane and cyclopentane derivatives. /ra .v-l,2-Disubstitutcd carbocyclic compounds are exclusively or predominantly formed with diastereomeric ratios in the range 80 20 100 0, strongly dependent on the conditions used to induce cyclization, i.e. heat, pressure or Lewis acid (MgBr2) catalysis227. 

Induction of asymmetry into the /J-lactam-forming process was inefficient with acyclic imines having chiral groups on the nitrogen [19] but efficient with rigid, cyclic chiral imines (Table 3). One of these was used as a chiral template to produce highly functionalized quaternary systems (Eq. 5) [34]. 

When either or both of the reaction components has a chiral substituent, the reaction can be enantioselective (only one of the four diastereomers formed predominantly), and this has been accomplished a number of times. Enantioselective addition has also been achieved by the use of a chiral catalyst and by using optically active enamines instead of enolates. Chiral imines have also been used. ... 

The use of chiral auxilliaries in the Staudinger reaction has been explored extensively. Chiral imines derived from (15)-(-t-)-camphor 10-sulfonic acid <96TA2733>,... 

Reactions of nitro compounds with chiral imines have only recently been described. Either chiral 1-phenylethylamine (auxiliary) or the glyceraldehyde acetonide aldehyde was used as the chiral precursors of the imines 66 and 68, which reacted with 3-mesyloxynitropropane to give the 3-nitropyrrolidines dl)-67 and 69, respectively, with good diastereoselectivity. In fact, both products were obtained (almost) exclusively as trans diastereomers with high level of asymmetric induction, but the configurations of the newly formed stereocenters were not determined [44] (Scheme 13). N-Boc imines can be formed... 

Scheme 13 Diastereoselective addition of a-nitrocarbanions to chiral imines...

Scheme 19 Asymmetric synthesis of 2-(l-aminoalkyl)pyrrolidines and 2,2 -dipyrrolidines from chiral imines and iminium ions...

Instead, the reaction of TMS cyanide with the chiral imine prepared from racemic 2-benzoylaminocyclohexanone and (fi)-l-phenylethylamine or (S)-l-phenylethylamine in the presence of zinc chloride occurred with low stereocontrol, and the two enantiomers of fra s-l,2-diaminocyclohexane car-boxyhc acid were isolated with low yields after several steps [88]. 

The test reaction was also investigated by Anderson et al. employing chiral imine-sulfide ligands derived from amino acids.The ligand of choice, depicted in Scheme 1.37, (S)-A-2 -chlorobenzylidene-2-amino-3-methyl-l-thiophenylbutane readily prepared from (5)-valinol, led to an enantioselectivity... 

Enantioselective Cyclopropanation. Enantioselective versions of both copper and rhodium cyclopropanation catalysts are available. The copper-imine class of catalysts is enantioselective when chiral imines are used. Some of the chiral ligands that have been utilized in conjunction with copper salts are shown in Scheme 10.10. 

The addition of 2-nitropropene to the chiral imine derived from 2-methylcyclopentanone and (S )-l-phenylethylamine gives the adduct in high regio- and stereoselectivity (Eq. 4.71).90 The product is converted to a chiral 1,4-diketone via the Nef reaction. 

NMR can be a powerful tool for determination of enantiomeric excess or absolute configuration of the optically active compounds, however, these processes require the use of some auxiliaries, for example, chiral lanthanide shift reagents or chiral derivatising agent. In many cases, the starting point for determination of enantiopurity of amines, amino acids or diols is the formation of chiral imines. 

During the past decade, the main focus of studies related to the well-known349 CeCl3- or SnCl2-catalyzed reactions of allylzinc and benzylzinc halides with imines was the application of polymer-supported chiral imines.350,351 An example of such reactions is shown in Scheme 135.350 It should be noted that attempts using arylzinc reagents in... 

To complement the above information, a highly enantioselective synthesis of a-amino phosphonate diesters should be mentioned.164 Addition of lithium diethyl phosphite to a variety of chiral imines gives a-amino phosphonate with good to excellent diastereoselectivity (de ranges from 76% to over 98%). The stereoselective addition of the nucleophile can be governed by the preexisting chirality of the chiral auxiliaries (Scheme 2-63). 

Increasing interest is expressed in diastereoselective addition of organometallic reagents to the ON bond of chiral imines or their derivatives, as well as chiral catalyst-facilitated enantioselective addition of nucleophiles to pro-chiral imines.98 The imines frequently selected for investigation include N-masked imines such as oxime ethers, sulfenimines, and /V-trimcthylsilylimines (150-153). A variety of chiral modifiers, including chiral boron compounds, chiral diols, chiral hydroxy acids, A-sull onyl amino acids, and /V-sulfonyl amido alcohols 141-149, have been evaluated for their efficiency in enantioselective allylboration reactions.680... 

The synthesis of optically active compounds by the diastereoselective reaction of allyltitanium reagents with chiral electrophiles has also been reported. The reaction of allyltitanium reagents with chiral imines proceeds with excellent diastereoselectivity, as shown in Eq. 9.28, thus providing a new method for synthesizing optically active homoallylic amines with or without a P-substituent [51,52],... 

In contrast to the allyltitaniums derived from acrolein cyclic acetals, such as 1,2-dicyclo-hexylethylene acetal shown in Scheme 9.8, those derived from acrolein acyclic acetals react with ketones and imines exclusively at the y-position. As shown in Eq. 9.29, the reaction with chiral imines having an optically active 1-phenylethylamine moiety proceeds with high diastereoselectivity, thus providing a new method for preparing optically active 1-vinyl-2-amino alcohol derivatives with syn stereochemistry [53], The intermediate allyltita-nium species has also found use as a starting material for a carbozincation reaction [54],... 

P-Lactams. Diketene can function as an equivalent to acetylketene, CH3C0CH=C=0, to provide 3-acetyl-p-lactams by [2 + 2]cycloaddition with imines.1 A stereoselective cycloaddition of this type can furnish a useful precursor (2) to lp-methylcarbapenems. Thus reaction of diketene with the chiral imine 1, prepared in a few steps from the readily available methyl (S)-3-hydroxy-2-meth-ylpropionate (Aldrich), can provide the desired 3,4-frpreviously developed for synthesis of the antibacterial carbapenem 4. 

Scheme 9.27 Kinetic resolution of an allenylzinc reagent using a chiral imine.

For a recent approach using chiral imines as starting material see Pfau, M. Revial, G. Guin-gont, A. d Angelo, J. J. Am. Chem. Soc. 1985, 107, 273. 

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. 

TiCl, on the silyl ketene acetal however, other data suggest that metal enolates may not be involved (73b). In subsequent studies, this reaction has been extended to chiral imines (81,82). 

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