Substrate-Directive Diastereoselective Hydrogenation

Most reports on diastereoselective oxidation of sulfides are substrate-directed. Diastereoselectivity has been achieved by either steric- or neighboring-group participation.21 Incipient hydrogen bonding between the substrate hydroxyl group and the incoming percarboxylic acid has been evoked to explain the high diastereoselectivity observed in the oxidation of 10-exo-hydroxy-bornyl- derivatives 7 and 9 (Scheme 1). The oxidation of 9 with m-CPBA in MeOH occurs without stereoselectivity. 

Diastereoselective Hydrogenation since -OH directs the H2, there is a possibility for control of stereochemistry - sensitive to H2 pressure catalyst cone, substrate cone, solvent. 

Other functional groups which have a heteroatom rather than a hydroxyl group capable of directing the hydrogenation include alkoxyl, alkoxycarbonyl, carboxylate, amide, carbamate, and sulfoxide. The alkoxy unit efficiently coordinates to cationic iridium or rhodium complexes, and high diastereoselectivity is induced in the reactions of cyclic substrates (Table 21.3, entries 11-13) [25, 28]. An acetal affords much lower selectivity than the corresponding unsaturated ketone (Table 21.3, entries 14 and 15) [25]. 

The difficulty of this task became obvious in an attempt to achieve a diastereoselective hydroformylation of a simple methallylic alcohol system. It was expected that in analogy to the known substrate-directed rhodium-catalyzed hydrogenation reaction, substrate direction via the hydroxyl substituent would control diastereoselectivity in the course of the hydro-formylation reaction [9], However, a completely stereorandom hydroformylation product formation was observed (1—>3) [10, 11]. 

In these reactions, the major diastereomer is formed by the addition of hydrogen syn to the hydroxyl group in the substrate. The cationic iridium catalyst [Ir(PCy3)(py)(nbd)]+ is very effective in hydroxy-directive hydrogenation of cyclic alcohols to afford high diastereoselectivity, even in the case of bishomoallyl alcohols (Table 21.4, entries 10-13) [5, 34, 35]. An intermediary dihydride species is not observed in the case of rhodium complexes, but iridium dihydride species are observed and the interaction of the hydroxyl unit of an unsaturated alcohol with iridium is detected spectrometrically through the presence of diastereotopic hydrides using NMR spectroscopy [21]. 

As described hitherto, diastereoselectivity is controlled by the stereogenic center present in the starting material (intramolecular chiral induction). If these chiral substrates are hydrogenated with a chiral catalyst, which exerts chiral induction intermolecularly, then the hydrogenation stereoselectivity will be controlled both by the substrate (substrate-controlled) and by the chiral catalyst (catalyst-controlled). On occasion, this will amplify the stereoselectivity, or suppress the selectivity, and is termed double stereo-differentiation or double asymmetric induction [68]. If the directions of substrate-control and catalyst-control are the same this is a matched pair, but if the directions of the two types of control are opposite then it is a mismatched pair. 

In the epoxidation of acyclic allylic alcohols (Scheme 6), the diastereoselectivity depends significantly on the substitution pattern of the substrate. The control of the threo selectivity is subject to the hydroxyl-group directivity, in which conformational preference on account of the steric interactions and the hydrogen bonding between the dioxirane oxygen atoms and the hydroxy functionality of the allylic substrate steer the favored 7r-facial... 

The diastereoselectivity dropped drastically in presence of protic methanol and totally disappeared for the corresponding silyl ethers. These data are in agreement with the presence of a hydroxy directing effect in the Patemo-Bilchi reaction. Threo stereoisomer can be favored through the formation of an hydrogen bond between triplet excited benzophenone and the substrate in the exciplex, while the formation of the erythro stereoisomer would be less favored due to allylic strain (Scheme 3.41). 

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