Diastereospecific reduction

This study shows that by combining the diastereospecific reduction of acylaze-tidin-2-ones and the suitable functional group manipulations, it has been possible to synthesize the 3-spiro-epoxyazetidin-2-ones in a diastereospecific manner. 

Diastereospecific reduction of an enone. A key step in a synthesis of the lichen macrolide (+ )-aspicilin (4) is the reduction of the oxodienelactone 2 to the dienol 3 with Yamamoto s reagent (1) in 96% yield. Dihydroxylation of 3 with 0s04 and pyridine followed by H,S reduction gives the triol (4) in 40% yield. 

Diastereospecific reduction of ferrocenic alcohols by ionic hydrogenation. 

Nucleophilic additions to (cyclohexadienone)Fe(CO)3 complexes (218) occur in a dia-stereospecific fashion (Scheme 56)197. For example, the Reformatsky reaction of ketone (218a) affords a simple diasteromeric alcohol product19715. The reduction of (1-carbo-methoxycyclohexa-l,3-dien-5-one)Fe(CO)3 (218b) to give 219 has been utilized in the enantioselective synthesis of methyl shikimate. In a similar fashion, cycloadditions of (2-methoxy-5-methylenecyclohexa-l,3-diene)Fe(CO)3 (220) occur in a diastereospecific fashion198. 

This reaction, derived from the Kursanov Fames reaction, consists of the reduction of an alcohol by a hydride in an acidic medium. In the case of a-ferrocenic alcohols this reaction takes place, in general, with retention of configuration due to the fact that the iron atom stabilizes the carbocation formed. However, diastereospecific reactions are observed when the substituents at the carbon atom bearing the hydroxyl group are bulky. Figure 2.75 shows that there is retention of configuration for one of the diastereomers and inversion for the other. 

Five carbasugar phosphates (14)-(18) have been successfully synthesized in either D or L, a or p forms from D-quinic acid (13) (Scheme 4). This synthesis included a novel, highly diastereospecific Pd/C-catalyzed cyclopropanol ring opening, diastereoselective reduction, dihydroxylation, the Mitsunobu reaction, and/or the Myers reductive 1,3-rearrangement, which were employed to install the desired stereochemistry. 

The most useful alternative measure of diastereoselectivity is the diastereomer ratio (d.r.) which, in contrast to d.e., is expressed not as a percentage but as a ratio. To take a simple example, if reduction of (55) gives (56) and (57) in a ratio of 90 10, the d.e. is 80% and the d.r. 9 1. For reactions in which two new stereogenic units are formed the diastereoselectivity is best expressed as the diastereomer ratio (see below). We do not favour the quantity % d.s. used by some authors.1 1 The terms diastereoselective and diastereospecific are used in an analogous way to enantioselective and enantiospecific. Note that a diastereomerically pure compound refers only to a pure enantiomeric pair of stereoisomers and gives no information on the ratio of the enantiomers present (see below). 

The great advantage of the Crabtree catalyst is that it is able to coordinate to Lewis basic groups in the substrate, thus directing the reduction to a specific face of the double bond. The diastereospecificity achieved is generally very high (Table 23.1), and such directed reductions have proved synthetically useful (Figure 23.30). 

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