Stereochemistry of carbonyl reduction

The stereochemistry of carbonyl reduction follows the same principles we have previously learned. Reduction converts a planar sp hybridized carbonyl carbon to a tetrahedral sp hybridized carbon. What happens when a new stereogenic center is formed in this process With an achiral reagent like NaBH4 or LiAlH4, a racemic product is obtained. For example, NaBH4 in CH3OH solution reduces 2-butanone, an achiral ketone, to 2-butanol, an alcohol that contains a new stereogenic center. Both enantiomers of 2-butanol are formed in equal amounts. 

C=X bonds The stereochemistry of the reduction of carbonyl compounds has been intensely studied with regard to synthetic and mechanistic aspects. The reduction of 1,2-diphenyl-l-propanone at a Hg cathode in aqueous EtOH and pH 8 affords the erythro alcohol as the major diastereomer (erythro threo = 5 to 1.4 1) [332]. This selectivity is in accord with a protonation of the intermediate anion, formed in an ECE sequence, from the least hindered side (Fig. 61). 

Stereochemistry of hydride reduction Hydride converts a planar sp -hybridized carbonyl carbon to a tetrahedral p -hybridized carbon. Thus, hydride reduction of an achiral ketone with LiAlH4 or NaBH4 gives a racemic mixture of alcohol when a new stereocentre is formed. 

The stereochemistry of the reduction is easy to explain as the molecule is folded in such a way tat only the bottom face of the carbonyl group is open to nucleophilic attack. The oxyanion rroduced can immediately cyclize to form the lactone. Clearly, this is possible only if the group - up, but it is also possible only if the C02Me groups are on this side of the molecule. The ijcmation of the lactone does prove the stereochemistry of the cycloaddition. 

The next step from the biosynthetic pathway is a branch point of the tropane alkaloid pathway [1,2]. Tropinone 24 is the first intermediate with a tropane ring, and it is converted into intermediates that lead to hyoscyamine 1 or calystegines production depending on the stereochemistry of the reduction [37], Two stereospecific tropinone reductases (TR EC 1.1.1.236) - tropinone reductase I (TR-I) reduces the 3-carbonyl group of tropinone 24 to the 3a-hydroxy group of tropine 27 and tropinone reductase II (TR-II) to the 3p-hydroxy group of pseudotropine 25. TR-I leads to hyoscyamine 1 and scopolamine 6 formation via tropine 27, whereas pseudotropine 25 produced by TR-II is converted into calystegines and other nortropane alkaloids [1, 7, 36]. 

Scheme 5 details the asymmetric synthesis of dimethylhydrazone 14. The synthesis of this fragment commences with an Evans asymmetric aldol condensation between the boron enolate derived from 21 and trans-2-pentenal (20). Syn aldol adduct 29 is obtained in diastereomerically pure form through a process which defines both the relative and absolute stereochemistry of the newly generated stereogenic centers at carbons 29 and 30 (92 % yield). After reductive removal of the chiral auxiliary, selective silylation of the primary alcohol furnishes 30 in 71 % overall yield. The method employed to achieve the reduction of the C-28 carbonyl is interesting and worthy of comment. The reaction between tri-n-butylbor-... 

The stereochemistry of 338 and 339 in each case results from initial conjugate addition of MeO" at position 2 of the chromone ring. Ensuing attack of the formed enolate 342 upon PhI(OMe)2 occurs in an anti manner because of steric interaction. Sequential addition of MeO to the carbonyl group of 343 gives 344, and intramolecular reductive elimination of C6H5I then occurs with inversion of configuration, 344 345. The reaction is... 

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