Catalytic system aldimine

In general, an aldimine is among the least reactive carbonyl compounds and is by far less reactive than an aldehyde [31-33]. Nevertheless, the Et2Zn-Ni catalytic system is successfully extended to the homoallylation of aldimine. Aldimine prepared in situ from an aldehyde and a primary aromatic amine undergoes the homoallylation smoothly under the essentially identical con-... 

Interestingly, fundamentally different stereoinduction mechanisms have been proposed for the activation of a number of related imine substrates, studies that resulted in the development of simple and highly effective new catalytic systems (27) for the addition of silyl ketene acetals to Al-Boc-protected aldimines (Mannich reaction) (Scheme 11.12c). ... 

Whiting et al. [20] found the catalytic system for an aza Diels-Alder reaction by the use of a combinatorial approach to catalyst selection. When methyl glyoxylate-derived aldimine 25 was reacted with Danishefsky s diene 24 in the presence of the chiral magnesium catalyst (10 mol %), prepared in-situ from chiral diphenylethylenediamine 23, Mgl2, and 2,6-lutidine, the Diels-Alder product 26 was obtained in 64 % yield with 97 % ee (Sch. 9). 

To avoid secondary reductive steps, low concentrations of the active low-valent metal are advantageous, i.e. the use of catalytic one-electron reduction cycles [31]. Low-valent vanadium species are efficient catalysts for pinacolization. After the primary electron transfer, the oxidized vanadium catalyst can be reduced by Zn(0) or by aluminum [32], TrialkyIsilanes have to be added to decomplex the oxidized vanadium catalyst from the pinacol [33]. The same catalytic system can also be used for the synthesis of 1,2-diamines via coupling of aldimines [34]. Alternatively, a titanium (Il)-samarium system gives the 1,2-diamines with moderate D,L-selectivity [35]. 

Hu et al. developed a system that involved cooperative catalysis by a chiral phosphoric acid and an achiral rhodium complex (Scheme 3.37) [81]. They applied the binary catalytic system to a three component coupling reaction among a diazoesters, primary alcohols, and aldimines. The steric bulkiness of the primary alcohol had a significant effect on both diastereo and enantioselectivities. The sterically demanding 9 anthracenemethanol was the best component to give p amino a alkoxy esters with excellent stereoselectivities under the combined and cooperative catalysis by phosphoric acid ll and the rhodium complex. 

In 2007, Feng et al. reported an efficient self-assembled catalytic system for the addition of trimethylsilyl cyanide to imines. The combined use of cinchonine (27), achiral 3,3 -(2-naphthyl)-2,2 -biphenol (28), and titanium tetra-isopropoxide gave an efficient catalyst for aldimines and ketimines (Scheme 7.19). Cinchonine induces a chiral environment around the titanium atom by fixing a stable chiral configuration to the biphenol ligand, and also activates hydrogen cyanide, generated in situ. In addition to trimethylsilyl cyanide, safer ethyl cyanoformate can be used with similar results. 

Additionally, the protocol proved not only applicable to aryl-substituted organo-metallics, but also enabled the use of an alkenyl boronic acid. Further, aldimine 11 was regioselectively arylated with this catalytic system, yielding-after subsequent hydrolysis-aldehyde 12 (Scheme 9.6) [17]. 

Lim and coworkers [102] examined the reaction of aldimines and ketimines with aikenes in the presence of [Rh(coe)2Cl]2/PCy3 (Scheme 19.71). Acidic hydrolysis of the produced imine provided the corresponding arylketone, ultimately rendering the overall transformation analogous to the Murai reaction. With this active catalytic system, the mono- and/or the dialkylated products were obtained in moderate to... 

Following the pioneering discovery by Oi and Inoue on the diarylation of imines [43], improved diarylation of imines was reached in NMP using a Ru(II)/KOAc/ PPhs catalytic system for aldimines and Ru(ll)/2 KOAc without PPhs but for longer time for ketimines. The diarylated imines could be reduced into bulky amines by catalytic hydrosilylation with the same Ru(ll) catalyst. Thus the overall reaction could be performed in two steps via sequential Ru(ll) catalysed C-H bond functionalization/hydrosilylation [(Eq. 19)] [84]. 

More importantly it was found that the ketimines could be more easily diarylated in water in basic medium (K2CO3) than in NMP using the Ru(II)/2KOAc/l PPh3 catalytic system [(Eq. 20a)] [85]. As ketones do not direct ortho C-H bond activation followed by arylation, this arylation of aldimines and ketimes can be used for the access to diarylated aldehydes and ketones that are thus obtained by acidification of their aqueous solution. Oxazoline can also efficiently direct ortho-arylation of aryl groups [(Eq. 20b)] [85]. 

The Cp2VCl2/R3SiCl/Zn catalytic system can be also applicable to the reductive coupling of aldimine (Scheme 2.24) [72], mew-Diamine 33 is obtained as a major product. The diastereoselectivity depends on the substituents on both the nitrogen and silane atoms. The allyl or benzyl group on the nitrogen atom is advantageous for me so selection. 

The potential substrates for the Strecker reaction fall into two categories ald-imines (derived from aldehydes, for which cyanide addition results in formation of a tertiary stereocenter) and ketoimines (derived from ketones, for which addition results in a quaternary stereocenter). As in the case of carbonyl cyanation, significant differences are observed between the substrate subclasses. To date, while a few catalyst systems have been found to display broad substrate scope with respect to aldimine substrates, successful Strecker reactions of ketoimines have been reported in only two cases. As is the case for all asymmetric catalytic methodologies, the breadth of the substrate scope constitutes a crucial criterion for the application of the Strecker reaction to a previously unexplored substrate. 

The enantioselective allylation of aldimines 8 with the tetraallylsilane-TBAF-MeOH system with use of the chiral bis-7i-allylpalladium catalyst 20a under catalytic, non-Lewis acidic, essentially neutral, and very mild reaction conditions has been achieved (Eq. 11) [9]. The reaction of imines 8 with 1.2 equivalents of tetraallylsilane 25d in the presence of 5 mol% of the chiral bis-Ti-allylpalladium catalyst 20a, 25 mol% of TBAF, and 1 equivalent of methanol in THF-hexane (1 2) cosolvent furnished the corresponding homoallylamines 9 in high yields and good to excellent enantioselectivities. 

The elegant process, developed by Merck chemists [20], involved a catalytic amount of aromatic aldehyde. This facilitates racemization of the wrong enantiomer (3f )-6, in solution at ambient temperature, via an aldimine intermediate, which possesses a significantly more acidic C(3)-H (pA a 12) than the parent amine (p a 20). Due to the significantly lower solubility of its (-i-)-camphor-lO-sulphonic acid (CSA) salt, the desired enantiomer, (3S)-6, continuously crystallizes from the system in equilibrium. This efficient one-pot resolution-racemization process has been used on a multi-kilo scale, affording (3S)-6 for production of various biologically active compounds. 

Despite the considerable synthetic potential of this reaction, only two NHC-containing catalysts have been reported to date. The in situ generated complex from the reaction between [RhCl(COD)]2 and the NHC-silver ligand transfer reagent 20 was found to be active in the arylation of an At-phosphi-noyl aldimine with phenylboronic acid but unfortunately only one catalytic test was performed [eqn (8.9)]. In a more systematic study, Suzuki and Sato screened various azolium salts, among which the system [RhCl(COD)]2/ lAd-HCl proved to be the most active catalyst for the arylation of a series of A -sulfonyl and A -phosphinoyl arylimines. ... 

The ring nitrogen of pyridoxal phosphate exerts a strong electron-withdrawing effect on the aldimine, and this leads to weakening of all three bonds about the a-carbon of the substrate. In nonenzymic model systems, all the possible pyridoxal-catalyzed reactions are observed a-decarboxylation, amino-transfer, racemization, and side chain elimination and replacement reactions. By contrast, enzymes show specificity for the reaction pathway followed which bond is cleaved will depend on the orientation of the Schiff base relative to reactive groups of the catalytic site. 

Asymmetric phase-transfer catalytic addition of cyanide to C=N, C=0, and C=C bonds has been recently explored, which has been demonstrated to be an efficient method toward the synthesis of a series of substituted chiral nitriles. In this context, Maraoka and coworkers disclosed an enantioselective Strecker reaction of aldimines by using aqueous KCN [140]. In this system, the chiral quaternary ammonium salts (R)-36e bearing a tetranaphthyl backbone were found to be remarkably efficient catalysts (Scheme 12.25). Subsequently, this phase-transfer-catalyzed asymmetric Strecker reaction was further elaborated by use of a-amidosulfones as precursor of N-arylsulfonyl imines. Interestingly, the reaction could be conducted with a slight excess of potassium cyanide [141] or acetone cyanohydrin [40] as cyanide source, and good to high enantioselectivities were observed. In contrast, the asymmetric phase-transfer-catalytic cyanation of aldehydes led to the cyanation products with only moderate enantioselectivity [142]. 

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