Reductions of Imines and Ketones

Complexation of [Cp IrCl2]2 with iV-heterocyclic carbenes has led to complexes such as 25, developed by Peris and coworkers [107, 108], and 133, developed by Crabtree and coworkers [12]. Complex 24 is activated by the addition of silver triflate and is effective for the iV-alkylation of amines with alcohols and for the iV-alkylation of anilines with primary amines. Complex 25 has also been shown to couple benzyl alcohol 15 with a range of alcohols, including ethanol 134, to give ether products such as ether 135 (Scheme 31). Complex 133 was an active hydrogen transfer catalyst for the reduction of ketones and imines, using 2-propanol as the hydrogen source. It was also an effective catalyst for the iV-alkylation of amines... 

Next, a few examples of asymmetric reductions with trichlorosilane are presented. An asymmetric reduction of ketones and imines was reported by Matsumura and coworkers by using trichlorosilane as reductant and A-formyl pyrrolidine derivative 36 as ligand (Scheme 28) [101, 102]. 

Oxazaborolidines have been found to be a unique catalyst for asymmetric borane reduction of ketones and imines [35,36]. Coordination of BH3 to the nitrogen atom of 24 serves to activate BH3 as a hydride donor and to increase the Lewis acidity of the boron atom (Eq. 9). The Lewis acidity of the boron atom in the oxazaborolidine plays an important role in the reduction. Several types of polymer-supported oxazaborolidine have been reported and are considered to be polymer-supported boron-based Lewis acids. 

Various sodium aminoaluminohydrides have been proposed for selective reduction of esters and aromatic nitriles to the corresponding aldehydes [CK3, CK5, CJl, YA2J. Chiral alkoxy- and aminoaluminohydrides have been used in asymmetric reductions of ketones and imines, and these will be described in the corresponding chapters (Sections 3.2.3 and 3.3.1). 

This new generation of iron precatalysts was tested for the reduction of ketones and imines, in both ATH and, most recently, ADH. In both cases, no induction period... 

The CATHy catalysts, like their ruthenium analogues are also active in the reduction of ketones and imines using the formate system [5], Wills has published on the reduction of ketones [9], and Baker on the reduction of imines [6], The development of this process for large-scale use has proven more complex and this will be described elsewhere in this chapter. 

Many experiments have been described for the PT reduction of ketones and imines with NaBH4 as reagent. The catalysts were ammonium salts of Cinchona alkaloids and ephedrine and even chiral crown ethers. Only medium enantiose-lectivities could be achieved. 

Table 1 Zn-Catalyzed Reduction of Ketones and Imines with PMHS in Media-nof...

In 1999 [22] and 2001 [23], Matsumura and co-workers reported the first examples of stereoselective hydrosilylation with HSiCla and (5)-proline derivatives as effective activators. These works can be considered as milestones for the asymmetric reduction of ketones and imines using HSiCla as reducing agent and paved the road to the synthesis of other related systems. Since then, considerable efforts have been devoted to the development of efficient catalysts for the reduction of carbon-nitrogen double bonds, and remarkable progress has been made. 

Transfer hydrogenation is particularly good for the reduction of ketones and imines that with H2 are somewhat more difficult to reduce than C=C bonds. 

Transfer hydrogenation is particularly good for the reduction of ketones and imines that are somewhat more difficult to reduce with H2 than are C=C bonds. Backvall has shown how RuCl2(PPh3)3 is effective at 80°C with added base as catalyst promoter. The role of the base is no doubt to form the isopropoxide ion, which presumably coordinates to Ru and by elimination forms a hydride and acetone. 

Used in conjuction with [Cp RhCl2]2 using HC02Na in water reduction of ketones and imines described, isoquinoline 93% e.e., p-carboiine 93% e.e. 

Another example was reported of the reduction of ketones and imines with a novel water-soluble chiral diamine 12 as the ligand in neat water (Fig. 18) [81]. Cyclic imines were reduced in high e.e. 

Synthetic highlights A variety of pathways have been taken in the synthetic approach to sertraline. These include stereoselective reduction of ketones and imines under kinetic and thermodynamic control, using diastereoselective or enan-tioselective catalysts and reagents, desymmetrization of oxabenzonorbomadiene followed by the Suzuki coupling of arylboronic acids and vinyl halides and Pd-Catayzed (Tsuji-Trost) coupling of arylboronic acids and allylic esters. For the production of sertraline, the simulated moving bed (SMB), a cost-effective technology, has been introduced. 

Stereoselective Reduction of Ketones and Imines Under Kinetic and Thermodynamic Control... 

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