Chiral compound stereoselective synthesis reduction products

In addition to stereoselective metalation, other methods have been applied for the synthesis of enantiomerically pure planar chiral compounds. Many racemic planar chiral amines and acids can be resolved by both classical and chromatographic techniques (see Sect. 4.3.1.1 for references on resolution procedures). Some enzymes have the remarkable ability to differentiate planar chiral compounds. For example, horse liver alcohol dehydrogenase (HLADH) catalyzes the oxidation of achiral ferrocene-1,2-dimethanol by NAD to (S)-2-hydroxymethyl-ferrocenealdehyde with 86% ee (Fig. 4-2la) and the reduction of ferrocene-1,2-dialdehyde by NADH to (I )-2-hydroxymethyl-ferrocenealdehyde with 94% ee (Fig. 4-2lb) [14]. Fermenting baker s yeast also reduces ferrocene-1,2-dialdehyde to (I )-2-hydroxymethyl-ferro-cenealdehyde [17]. HLADH has been used for a kinetic resolution of 2-methyl-ferrocenemethanol, giving 64% ee in the product, (S)-2-methyl-ferrocenealdehyde... 

Compound 310 has been used in a stereoselective synthesis of (iS)-4,5-dihydro-4-methyl-2(3//)turanone (315) (Scheme 42), an important chiral building block. After reduction of the ester, protection of the primary alcohol, removal of the EE group, and tosylation of the secondary alcohol, reaction with di- er butyl malonate gives 313 with 97% inversion of configuration [107]. Hydrolysis, debenzylation, lactonization, and decarboxylation furnishes the product 315 (93% ee). 

The chiral pool refers to readily available optically active natural products, some of which are commercially used in quantities of 10 -10 tonnes per year [5], Among them, the most inexpensive compounds are a-amino acids, like monosodium L-glutamate, or carbohydrates, like dextrose or sorbitol. The success of the second method depends on the availability of particular catalysts. One rather special example, how efficient stereoselective synthesis can work, is the syn-selective aldol reaction followed by a stereoselective alkene hydroboration and ketone reduction (Figure 1.8) which were used by Paterson et aJ. [26] to synthesize intermediates for the antibiotic oleandomycin. According to Paterson et al., four new stereocenters are formed in only two synthetic steps [9]. For the purpose of separating racemic mixtures... 

To date, two total syntheses of myriaporone 4 are known. This chapter is based on the total synthesis of myriaporone 4 published by Taylor et al. in 2004. The synthesis of a chiral precursor, which has also been employed for the total synthesis of related compounds, was published by the same group in 1998. The linear total synthesis starts with an enantiomerically pure molecule from the chiral pool that delivers the stereogenic center at C-12 of the final product, employs Evans aldol reactions as key steps for stereoselective chain elongations and additionally includes reduction/oxidation steps as well as protecting group chemistry. 

This cyclization has been used in an efficient synthesis of chokol A 11.219, an anti-fungal compound (Scheme 11.74). The acetal 11.216, in which the tartrate moiety functions as an economical chiral auxiliary, cyclized using palladium acetate to give an 8.5 1 mixture of stereoisomers. Aeidic hydrolysis removed the acetal to give a ketone 11.217, which could be taken through to the natural product 11.219 by selective reduction of the electron-poor alkene, stereoselective addition of a methyl group, allylic oxidation and desilylation. 

Chiral (3-hydroxy esters are versatile synthons in organic synthesis specifically in the preparation of natural products [68-70]. The asymmetrical reduction of carbonyl compounds using baker s yeast has been demonstrated and reviewed [5,71,72]. In the stereoselective reduction of P-keto ester of 4-chloro- and 4-bromo-3-oxobutanoic acid, specifically 4-chloro-3-oxobutanoic acid methyl ester, Sih and Chen [73] demonstrated that the stereoselectivity of yeast-catalyzed reductions may be altered by manipulating the size of ester group using y-chloroacetoacetate as substrate. They also indicated that the e.e. of the alcohol produced depended on the concentration of the substrate used. Nakamura et al. [74] demonstrated the reduction of p-keto ester with baker s yeast and controlled... 

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