Imines cyclic, hydrogenation

The cyclic imine was hydrogenated to form the dibenzotetraaza-14-crown-4 ligand. This cyclization reaction was carried out in the absence of a metal ion template. It is possible that internal hydrogen bonding in the starting tetraamine acts as a template to help in the cyclization process. 

The photoreduction of imines is not as well understood as that of carbonyl compounds. Padwa et a/. 9 have suggested that the low reactivity of imines towards hydrogen abstraction may be a result of twisting about the C=N bond, which leads to rapid radiationless decay of excited imine. Such a process cannot be the only factor involved, because the cyclic imine (31),70 where syn-anti isomerization is prohibited, only shows reactivity comparable with that of the acyclic imine iV-benzyl i denecyclohexylamine.69 It is also reported that the cyclic imines (33) and (34) undergo photoreduction in propan-2-ol to... 

Enantiocontrol of hydrogenation of geometry-fixed cyclic imines seems easier than that wifli flexible, acyclic imines. The chiral titanocene catalyst 34 exhibits excellent enantioselection in hydrogenation of various cyclic imines [346, 352]. For example, 2-phenyl-l-pyrroUne (R = C5H5, = CHj), a five-membered imine, is hydrogenated with an R catalyst to give (R)-2-... 

Scheme 8.5 Buchwald s example of asymmetric hydrogenation of cyclic imine.

Asymmetric hydrogenation of a cyclic enamide (Approach B) had very sparse literature precedents [7]. It should also be noted that preparation of these cyclic imines and enamides is not straightforward. The best method for the synthesis of cyclic imines involves C-acylation of the inexpensive N-vinylpyrrolidin-2-one followed by a relatively harsh treatment with refluxing 6M aqueous HC1, which accomplishes deprotection of the vinyl group, hydrolysis of the amide, and decarboxylation (Scheme 8.6) [8]. 

The asymmetric hydrogenation of acyclic imines with the ansa-titanocene catalyst 102 gives the chiral amines in up to 92% ee.684,685 This same system applied to cyclic imines produces the chiral amines with >97% ee values.684,685 The mechanism of these reductions has been studied 686... 

As illustrated in the hydrogenation of cyclic imines, the system is compatible with a wide range of functional groups, such as olefins, protected or unpro-... 

Table 6.5 Enantioselective hydrogenation of cyclic imines catalyzed by [(R,R,R)-(EBTHI)TiX2],...

In summary, the most popular hydrogen donors for the reduction of ketones, aldehydes and imines are alcohols and amines, while cyclic ethers or hydroaromatic compounds are the best choice for the reduction of alkenes and alkynes. 

Kinetic resolution results of ketone and imine derivatives are indicated in Table 21.19. In the kinetic resolution of cyclic ketones or keto esters, ruthenium atrop-isomeric diphosphine catalysts 25 induced high enantiomer-discriminating ability, and high enantiopurity is realized at near 50% conversion [116, 117]. In the case of a bicyclic keto ester, the presence of hydrogen chloride in methanol served to raise the enantiomer-discriminating ability of the Ru-binap catalyst (entry 1) [116]. 

Ru-diphosphine-diamine complexes developed originally by Noyori for the hydrogenation of aryl ketones are also suitable for the hydrogenation of imines. The best results are obtained for N-aryl imines where a Ru-duphos-diamine complex achieved up to 94% ee, albeit with relatively low activity and productivity (entry 3.7) (for data relating to cyclic imines, see Table 34.5). 

Cyclic imines do not have the problem of syn/anti isomerism and therefore, in principle, higher enantioselectivities can be expected (Fig. 34.8). Several cyclic model substrates 6 were hydrogenated using the Ti-ebthi catalyst, with ee-val-ues up to 99% (Table 34.5 entry 5.1), whereas enantioselectivities for acyclic imines were <90% [20, 21]. Unfortunately, these very selective catalysts operate at low SCRs and exhibit TOFs <3 h-1. In this respect, iridium-diphosphine catalysts, in the presence of various additives, seem more promising because they show higher activities. With several different ligands such as josiphos, bicp, bi-... 

Table 34.5 Selected results for the enantioselective hydrogenation of cyclic imines (for structures, see Fig. 34.8) Catalytic system, reaction conditions, enantioselectivity, productivity and activity.

Cyclic imines 8 and 9 are intermediates or models of biologically active compounds and can be reduced with ee-values of 88 to 96% using Ti-ebthi, Ir-bcpm or Ir-binap in the presence of additives (entries 5.7, 5.9), as well as with the transfer hydrogenation catalyst Ru-dpenTs (entries 5.8, 5.10-5.12). As pointed out earlier, Ru-diphosphine-diamine complexes are also effective for imines, and the best results for 7 and 8a were 88% and 79% ee, respectively [36]. Azirines 10 are unusual substrates which could be transfer-hydrogenated with a catalyst prepared in situ from [RuCl2(p-cymene)]2 and amino alcohol L12, with ee-values of 44 to 78% and respectable TOFs of up to 3000 (entry 5.13). 

The reduction of imines and iminium salts present a particular difficulty in that those which are N-substituted can exist in different geometrical isomers that are reduced at different rates and with different selectivities. One way to overcome this problem is to use cyclic imines that can exist only as cis isomers. Although these are good substrates, this is not a general solution. The cyclic amines produced by transfer hydrogenation, together with best reported enantiomeric excesses, are listed in Table 35.6. Primary amines are difficult to pre-... 

Particularly noteworthy is the discovery of a new type of the active catalyst 99,103,104 a crystalline, air-stable yellow-orange solid, which can serve as a highly enantioselective tool in the titanium-catalyzed hydrosilylation of imines. The reaction can be highly stereoselective for both acyclic and cyclic imines under a wide range of hydrogen pressures (Scheme 6-46). 

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