Diastereoselectivity hydroxyl-group directivity

Photocyclization of benzophenone with chiral allylic alcohols, 9 (R = Me, Et, Pri, and Bu1) is hydroxyl group-directed to give regioselectivity and t/zreo-diastereoselectivity in the formation of mainly 10 <00JA2958>. 

In entry 15 of Table 21.10, it is noted that even a remote hydroxyl group directed hydrogenation by the cationic [Rh(diphos-4)(nbd)]+ catalyst to afford a moderate diastereoselectivity (80 20) [23]. This is an interesting example of long-range 1,5-asymmetric induction. 

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 hydroxyl-group-directed hydrogenation was carried out in the presence of 4mol% of Crabtree s catalyst [Ir (PCy3)(Py)(COD)]PF6 in 1,2-dimethoxyethane (DME) at 0°C and led to the formation of desired product (1S,3R)-257 with high yield (94%) and diastereoselectivity dr=>50l ). 

An interesting variant involves the use of an allylic alcohol as the alkene component. In this process, re-oxidation of the catalyst is unnecessary since the cyclization occurs with /Uoxygen elimination of the incipient cr-Pd species to effect an SN2 type of ring closure. Both five- and six-membered oxacycles have been prepared in this fashion using enol, hemiacetal, and aliphatic alcohol nucleophiles.439,440 With a chiral allylic alcohol substrate, the initial 7r-complexation may be directed by the hydroxyl group,441 as demonstrated by the diastereoselective cyclization used in the synthesis of (—)-laulimalide (Equation (120)).442 Note that the oxypalladation takes place with syn-selectivity, in analogy with the cyclization of phenol nucleophiles (1vide supra). 

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]. 

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]. 

In the case of cyclopentenyl carbamate in which a directive group is present at the homoallyl position, the cationic rhodium [Rh(diphos-4)]+ or iridium [Ir(PCy3)(py)(nbd)]+ catalyst cannot interact with the carbamate carbonyl, and thus approaches the double bond from the less-hindered side. This affords a cis-product preferentially, whereas with the chiral rhodium-duphos catalyst, directivity of the carbamate unit is observed (Table 21.7, entry 7). The presence of a hydroxyl group at the allyl position induced hydroxy-directive hydrogenation, and higher diastereoselectivity was obtained (entry 8) [44]. 

Keck showed that protection of the (1-hydroxyl group in (5-hydroxy ketones as tert-butyldimethylsilyl and benzyl ethers shut off reduction and starting material was recovered. This underlines the importance of pre-coordination of Sm(II) to the free hydroxyl in the directed reduction.13 The mm -selective reduction does, however, tolerate methyl, MOM, MTM and MEM ethers, presumably as these small ether groups still allow coordination to Sm(II).14 Keck pointed out that care should be taken when working with different systems as selectivities can be very substrate dependent.13 Flowers has also shown that the diastereoselectivity of the reduction can be altered by changing the reaction conditions through the use of other solvents or reaction protocols.15,16... 

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. 

The diastereoselectivity was significantly diminished when the hydroxyl was replaced with an ether or by hydrogen. Based on this and DFT calculations, the authors propose a counterion-directed reaction where acetate both coordinates to the allyl cation hydrogen atom and the hydroxyl group as illustrated in 283. 

Modena and colleagues47 have developed use of some chiral, non-racemic terpene alcohols as directing groups for highly diastereoselective m-chloroperbenzoic oxidation of sulfides into sulfoxides. Specifically the isobornyl vinylic sulfides 8 undergo hydroxyl-directed oxidation to give a 9 1 ratio of diastereomeric sulfoxides (equation 11). 

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