Aryl ketimines

Iridium-Catalyzed Asymmetric Hydrogenation of Olefins with Chiral N,P and C,N Ligands 71 Table 18 Asymmetric hydrogenation of acetophenone based A-aryl ketimines... 

Essentially, aU studies have used acetophenone-based iV-aryl ketimines as substrates or derivatives thereof. Some of the iV-aryl groups are easily deprotected to yield branched a-aryl primary amines, which can be further functionalized. 

The Br0nsted acid catalyzed enantioselective reduction of several methyl-aryl ketimines affords the corresponding amines in good yields and enantioselectivities (Table 4.1). The mild reaction conditions and generally good chemoselectivity of this transfer hydrogenation render this transformation an attractive and metal-free approach to optically active amines. 

Alkyl aryl ketimines were reduced with up to 99% ee (Scheme 8) [24]. The high enantioselectivity was not affected by the E Z ratio of the imines. For example, a 1.8 1 E Z mixture of the N-propylimine of 4 -methoxy-3-methyIbuty-rophenone was converted to the desired product in 97% optical yield. Hydrosilylation of the N-propylimine of cyclohexyl methyl ketone with a substrate to Ti molar ratio of 2,000 1 was completed to give the product in 98% ee [24]. N-Benzylimine of 2-octanone, a simple aliphatic ketimine, was reduced with 69% optical yield. The reduction of W-benzyl-l-indanimine gave the corresponding amine in 92% ee (Scheme 9) [24]. 

In general, differently substituted alkyl and aryl ketimines, including a-imino esters, can be reduced in good to excellent yields (Table 1). 

Many of the alkyl aryl ketimines have been isolated for further study. 

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. 

The same group [50] developed a remarkable enantioselective synthesis of chiral indenylamines 179 via domino Rh(I)-catalyzed C-H activation/cyclization of aryl ketimines 177 and internal alkynes 170 (a formal [3+2] cycloaddition) (Scheme 3.46). A major challenge of this transformation was the requirement of a catalyst that could accommodate the many different steps in the reaction sequence and show selectivity for instance, imine-directed ortho C-H activation/... 

The possibilities for the formation of carbon—carbon bonds involving aromatic compounds have been enormously enhanced by the use of transition metal catalysts, and this area has been the subject of several reviews. Some of these concentrate on the applications of specific metals, and there have been surveys of the use of compounds of silver, copper and nickel,mthenium, and palladium in catalysis. The metalation of carbon-hydrogen bonds, preceding functionalization, may be aided by carboxylate ions, and this subject has also been reviewed. There is evidence here for concerted base-assisted deprotonation as shown in (10). In the carboxylate-assisted reaction of aryl ketimines with alkyl halides, a ruthenium-bonded intermediate (11) has been proposed, which subsequently adds the alkyl halide. " ... 

PMHS). One example of these reactions is shown in Equation 16.38d. These reactions have also been extended to highly enantioselective hydrosilylations of N-phosphoryl aryl ketimines (Equation 16.38e). ... 

Formation of aromatic nitriles by basic hydrolysis of trichloromethyl aryl ketimines. Acidic hydrolysis yields ketones ... 

Sun and co-workers developed a novel Lewis basic organocatalyst 86 (Scheme 31), easily synthesized from commercially available L-pipecolinic acid. The catalyst 86 promoted the reduction of IV-aryl ketimines 85 with HSiCl3 2 in high yield and... 

Further cyclopropyl aryl ketimine rearrangements have been noted, and bicyclo[3,l,0]hex-3-enones undergo rearrangement via keten intermediates. ... 

Diaryl ketimines are more stable than alkyl aryl ketimines which in turn are more stable than the purely aliphatic ketimines since conjugation increases the thermodynamic stability of the azomethine linkage Benzophenone imine (3), with a melting point of 48°c is quite stable . Although the monoimine of j>-benzoquinone is very unstable, the diimine (4) is sufficiently stable to be studied spectroscopically . V... 

In addition, the asymmetric reduction of A7-aryl ketimines with tri-chlorosilane could be achieved on polymer-supported organocatalysts by Kocovsky et alP Indeed, 7V-methylvaline-derived formamide anchored to a polymeric support, used at a catalyst loading of 15 mol %, allowed good enantioselectivities of up to 82% ee combined with good yields to be obtained for the formed chiral amines (Scheme 8.3). This novel methodology simplified the recovery of the catalyst, which could be reused at least five times without any loss of the activity. The best results were obtained with the catalysts directly attached to the polymer or via a suitable spacer. A strong influence of the solvents on the catalytic performance was observed with chloroform giving the... 

The involvement of A7-aryl ketimines as substrates undoubtedly limits their applications since the aryl group on the nitrogen atom of the resulting amine in... 

Scheme 8.3 Reductions of 7V-aryl ketimines catalysed by polymer-supported organocatalyst.

Rhodium(I) catalyses adynamic kinetic asymmetric [3+2] annulation of aryl ketimines with racemic allenes, with good /Z-selectivity and up to 98% ee cw-Homoenolate equivalents have been generated from cts-enals using NHC catalysis they react with a,/0-unsaturated imines to form chiral cyclic ketone products. Their reactivities and stereoselectivities contrast with the better known trans-emls. 

Recently, Yamakawa and Yoshikai attempted to extend this chemistry to aryl aldimines. Limited success was achieved under the reaction conditions previously reported for aryl ketimines. However, careful screening and re-optimization of the reaction conditions eventually led to the desired addition products 28-33 in modest yields when tris(3-methylphenyl)phosphane (P(3-CH3QH4)3) and l-PrMgBr were used instead of P(3-C1C6H4)3 and t-BuCH2MgBr. 

The authors also demonstrated that a similar catalytic system could be used to promote the addition of aryl ketimines to aliphatic olefins at elevated temperatures with good success to produce the desired products 116-119 after acid-catalyzed hydrolysis. 

Chen T, Chen X, Wei J, Lin D, Xie Y, Zeng W (2016) Copper-eatalyzed cascade cycloamination of a-C p -H bond of N-aryl ketimines with azides aceess to quinoxalines. Org Lett 18(9) 02078-02081... 

To test this possibility, Ba ckvaU studied the reduction of the A -aryl ketimine 19 in which the imine and intramolecular amine trap are linked by a saturated cyclohexane ring. Reduction of 19 by 2 occurred at 80°C to give exclusively 20, in which the newly reduced amine was coordinated to ruthenium (Scheme 17) [25]. Upon warming to 8°C, 20 rearranged to 21. NMR experiments were also carried out where the imine nitrogen part of 19 was marked with At —80°C, only 20 could be observed in the NMR. Backvall concluded that these experiments support the inner-sphere mechanism. 

In 2008, Jones et cd. disclosed a stoichiometric Rh(III)-mediated reaction of JV-benzylidenemethylamine with dimethyl acetylenedicarboxylate to give the corresponding isoquinolinium salt [52a]. Inspired by this work, in 2012 we developed a Rh(III)-catalyzed one-pot synthesis of isoquinolinium salts 104 from benzaldehydes, primary amines, and internal alkynes by C-H activation and annulation [52b]. This was the first report for the synthesis of isoquinohnium salts by catalytic C-H activation. It is noteworthy that the current procedure was successfully apphed to the total synthesis of isoquinolinone alkaloid oxy-chelerythrine 105 (Eq. (5.99)). In 2013, our group and Huang independently found that various isoquinohnium salts could be synthesized from aryl ketimines, 2-phenyl pyridines, and alkynes under similar reaction conditions, as shown in Eqs. (5.100)-(5.102) [52c-e]. 

In 2001, Ellman and coworkers demonstrated the annulation of aryl ketimines with substituted olefins tethered to the meta position to provide the... 

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