Acyclic ketimines

Table 4. oc-Alkylated Acyclic Ketones by Alkylation of Chiral Acyclic Ketimines, Followed by Hydrolysis3... 

Highly enantioselective hydrogenation of acyclic ketimines is difficult to achieve [ 1 -4], primarily due to the ease of interconversion between the E and Z isomers in solution [5]. Chiral catalysts are required to reduce one stereoisomer preferentially, or to reduce both isomers with the same sense of enantioselection. 

Fortunately, the use of lithiated hydrazones derived from (S)- or ( )-l-amino-2-methoxymethylpyiro-lidine (SAMP or RAMP) as nucleophiles for asymmetric alkylations have provided a solution to the problems described above with metallated acyclic ketimines and aldimines. Lithiated SAMP or RAMP hydrazones of cyclic ketones are also alkylated in high yields. A major advantage of these chiral hydrazones is that their derivatives of aldehydes, acyclic and cyclic ketones all yield mainly ( )cc-. (Z)cN-Iithiated species on deprotonation with LDA in ethereal solvents under kinetic control. The ( )cc-configuration obtains as a result of the minimization of steric interactions in the usual closed transition... 

Scheme 3.40 Transfer hydrogenation of acyclic ketimines using Hantzsch ester...

The acid-catalyzed reaction of acetophenone with acyclic secondary amines results in the formation of the expected enamine and a rearrangement product. The latter product arises from the transfer of one of the amino N-alkyl groups to the cnamine s carbon to produce a ketimine (53a). 

The anions of (/ )-a-sulfinyl ketimines undergo 1,4-addition to cyclic a./Tunsaturated esters and then cyclization to give predominately c/.v-fused annulation products243. These studies have been extended to include acyclic a,/l-unsaturated esters 24b,c. 

Enantioselective exocyclic, endocyclic, and acyclic a-p-tolylsulfinyl ketimines have been reacted with Et2AlCN 45 The cyclic substrates exhibit good yield and diastere-oselectivity, but the acyclic cases are complicated by imine-enamine equilibria. 

The nucleophilic activation of hydrosilanes as HSi(OR)3 offers an opportunity to transfer one hydride on the carbon of ketones or imines [22]. The enantioselective organocatalytic hydrosilylation of ketones was first reported in 1999 by Matsu-mura et al. [23], the catalyst employed being a proline derivative 19 (Scheme 11.7). Amide 20 was also able to catalyze the hydrosilylation of ketimines, as indicated in Scheme 11.7 [24]. Improved results were recently reported by Kocovsky and Maikov [25], who prepared from valine some acyclic analogues of prolina-... 

Iminium salts bearing a labile trimethylsilyl group can be generated in situ and undergo nucleophilic addition (see Sections 1.12.4.2 and 1.12.7.3). Bis(trimethylsilyl)methoxymethylamine (75), for example, has been used as a formaldehyde equivalent for the preparation of primary amines. Cyclic imines, such as 3,4-dihydroquinolines, react with trimethylsilyl triflate (TMS-OTf) to provide reactive labile iminium salts (55), which condense with picoline anions. The addition of nonstabilized Grignard and organolithium reagents to acyclic aromatic ketimines and aldimines, however, is often not facilitated by the presence of TMS-OTf ... 

The asyininetric hydrogenation of imines provides an efficient and direct route for the synthesis of chiral amines. Zhu et al. [27a] reported a highly efficient asymmetric hydrogenation of acyclic A -aryl ketimines catalyzed by lr-(5 5)-25a under ambient pressure with excellent enantioselectivities (up to 91% ee) (Scheme 24). The high rigidity and bulkiness of the ligands 25 efficiently prevents the trimerization of the catalysts Ir-25 and maintains the stability of the catalysts under hydrogen atmosphere. 

Not for general application is the reaction of enamines with tetramethylthiuram disulfide/ triethylamine/hydrogen sulfide since the enamines of aliphatic aldehydes do not react at all and the ketimines of acyclic dialkylketones give only moderate yields (10-35%), whereas the enamines of cyclic or of aryl substituted ketones give the corresponding l,3-dithiole-2-thiones in fair to good yields (35-90%) <75JPR123>. 

Acyclic dialkylamines are not very reactive as nucleophiles in the oxidative alkylamination, however they are very prone to oxidation and, therefore, they are capable for unexpected behavior. Presumably, transformation 33 41 starts from oxidation of dialkylamme into imine 42, that is in equilibrium with enamine 43 (Scheme 28). The latter, as bifunctional C,W-nucleophile, attacks C-4 atom of the pyridazine ring to form cr -adduct 44, which then undergoes oxidative aromatiza-tion. Subsequent intramolecular oxidative amination of the intermediate 45 yields pyrrole derivative 41. The participation of imines in this process has been confirmed experimentally. In the presence of AgPy2Mn04, pyrimidopyridazine 33 reacts with authentic aldimines and ketimines 42 to give pyrroles 41. Transformation 33 41 represents not only a rare example of the tandem processes but... 

The P-chirogenic organocatalysts 294 and 295 were found to promote the enantioselective aza-Morita-Bayhs-Hillman reaction of ketimines derived from acyclic a-keto esters. In the P-chirogenic organocatalyzed aza-Morita-Baylis-Hillman reactions, a,a-disubstituted a-amino acid derivatives 296 were obtained in high yields and with high enantioselectivities (up to 97% cc) (Scheme 98) [195]. 

The first models for asymmetric induction in [2 + 2] cycloadditions are ketimines derived from precursors such as (25), which react with both cyclic and acyclic alkenes to give adducts with high enantiomeric excesses. Full details have been reported on the regio- and stereo-specificity of the addition of dichloroketene to 1-substituted cyclohexenes. Methyl (phenylthiomethyl)-ketene (26) provides a further example of a ketene which, after cycloaddition to cyclopentadiene, undergoes facile opening of the cyclobutane that is thus formed to provide vicinally substituted cyclopentene derivatives. ... 

A facile and effective enantioselective addition of terminal 1,3-diynes to acyclic a-Cp3 ketimine esters has been developed using zinc/BINOL complexes. The reaction works well with a variety of aromatic-, aliphatic-, and silyl-substituted diynes, providing the desired products in up to 97% enantiomeric excess. 

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