Chiral Alcohols and Amines

Many enantiopure alcohols and some amines have been used to prepare P-stereogenic compounds in optically pure form. The most relevant examples are given in this section. 

The racemic phosphide anion solutions were prepared by selective cleavage of one of the o-substituted phenyl rings by sodium/potassium alloy. These solutions were reacted with 102 and furnished a near-statistical mixture of (/)- and ( )-103, indicating no carbon-to-phosphorus chiral induction. The optically pure ligands could only be obtained, after considerable effort, by coordination to molybdenum moieties, separation and decomplexation. 

Series of w(phosphines) with a tra ,s-l,2-disubstuted pyrrolidine backbone were 

Diphosphines 106 were obtained by attack of phosphides to bi5(mesilate) 104, ° by cleavage of phenyl groups in 105 and alkylation of the obtained Aw(phosphide) ° ° or by other methods.Usually a mixture of the three possible diastereomers of 106 was formed although they could be often separated after complexation to palladium.  

In this synthesis two cleavages of the phenyl-phosphorus bond by lithium afforded, after hydrolysis, the Aw(secondary) phosphine borane 109, which underwent cyclisation with dichloromethane upon deprotonation giving the 

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Among the most active catalysts for the asymmetric transfer hydrogenation of prochiral ketones and imines to chiral alcohols and amines are arene-ruthenium(II) amino-alcohol (or primary/ secondary 1,2-diamine)-based systems, with an inorganic base as co-catalyst, developed by Noyori139-141 and further explored by others (Scheme 27).142-145... 

Catalytic sol-gel lipase immobilizates were rapidly commercialized (by Fluka) after their invention in 1995 because of their remarkably stable activity in esterification reactions (and also in the kinetic resolution of chiral alcohols and amines) along with unique stability (residual activity of 70% even after 20 reaction cycles is common). The original procedure for the encapsulation produced by the fluoride-catalysed hydrolysis of mixtures of RSi(OCH3)3 and Si(OCH3)4 has been improved... 

From unsymmetrical propargyl alcohol and propargyl amine derivatives as coupling partners of diynes, the corresponding axially chiral alcohols and amines were obtained in almost perfect diastereo- and enantioselectivities (Scheme 11.13). 

Iridium complexes are known to be generally less active in hydrosilylation reactions when compared to rhodium derivatives, although iridium-based catalysts with bonded chiral carbene ligands have been used successfully in the synthesis of chiral alcohols and amines via hydrosilylation/protodesilylation of ketones [46-52] and imines [53-55], The iridium-catalyzed reaction of acetophenone derivatives with organosubstituted silanes often gives two products (Equation 14.3) ... 

Scheme 6.5 A Kinetic resolution of chiral esters or amides in water B kinetic resolution of chiral alcohols and amines in organic solvents.

An excellent example of the successful combination of chemo- and biocatalysis in a two-step cascade process is provided by the dynamic kinetic resolutions (DKR) of chiral alcohols and amines. We first suggested [6], in 1993, that (de)-hydrogenation catalysts should be capable of catalyzing the racemization of chiral alcohols and amines via a dehydrogenation/hydrogenation mechanism as shown in Fig. 9.1. 

Dinitrobenzoyl derivatives of chiral alcohols and amines, trbger base, benzoin, binaphthol, etc,... 

Electroreductive deprotection of tosylates and sulfonamides of chiral alcohols and amines, respectively, was achieved without racemization [394,395]. 

Literature on the hydrosilylation of ketones and imines is extensive. This chemistry provides a method for the reduction of these unsaturated substrates with reagents that are inexpensive and either liquids or solids, rather than gases (H ). As noted in the introduction, much of this literature focuses on the enantioselective hydrosilylation of ketones and imines to form non-racemic chiral alcohols and amines. In addition to the conveniaice of using a liquid reagent, the ability to vary the substituents on a silane allows for tuning of the stereoselectivity of the reductions. 

Part two (section 3) deals with the hydrosilylation of unsaturated carbon-heteroatom bond, mostly 0=0 and 0=N (but also C N, and C=S), as a catalytic method for the reduction of C=0 and C=N bonds—one of the most fundamental transformations in organic chemistry. Catalytic hydrosilylation of prochiral ketones and imines with substituted silanes and siloxanes that can provide (if followed by hydrolysis) convenient access to chiral alcohols and amines, respectively, discussed from the catalytic and synthetic point of view completes this part. 

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