Alkenes diastereoselective hydroxylation

Diastereoselective hydroxylation has also been observed at an alkenic center in an acyclic system that is guided by a sulfoxide group that is more remote than the homoallylic position. Alkenes (18 equation... 

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). 

To connect the C2 and C3 atoms of the 1-hydroxyethylene moiety, Wuts et al.[341 and Poss and Reid 35 used the Wadsworth-Emmons reaction between a (3-amino-a-hydroxy-aldehyde and a phosphonate (two-carbon fragment) to give the desired isostere after reduction of the alkene. In the synthesis reported by Poss and Reid (Scheme 17) the stereochemistry of the hydroxyl group at C4 is established by a highly diastereoselective aldol addition to furan. A slight modification was employed by Chakravarty et all36 and Plata et al.[37 where 4-amino-3-oxo phosphonates were reacted with an aldehyde or ketone form of the two-carbon fragment. 

In a recent re-examination of the thermolysis of benzocyclobutenes for the in situ generation of o-quinodimethanes, the resultant IMDA diastereoselectivity was highly dependent on the nature of the hydroxyl protective group.90 The intramolecular 4 + 2-cycloaddition of o-quinodimethanes (83), derived from ene-bis(sulfinylallenes) (82), with electron-deficient and electron-rich alkenes produced the corresponding polycyclic aromatic compounds (84) (Scheme 22).91 The enantioselective Diels-Alder... 

The hydroxyl group at the allylic position has a significant effect on the syn/anti methyl stereoselectivity [67,68] and the diastereoselectivity [63,64] of the photo-oxygenation ene reaction (see Sec. II.B). To assess the effect of the hydroxyl at the more remote homoallylic position, the reaction of O with the geminal dimethyl trisubstituted homoallylic alcohols (85, 86, 89) and the cis dis-ubstituted 90 was examined in nonpolar solvents [116], The regioselectivity trend was compared with that of the structurally similar trisubstituted alkenes (87, 88, 91) [105], The results are summarized in Table 12. 

In the analysis of multiple stereochemical influences, if is useful fo classify the stereoselectivity as substrate (reactant) controlled or reagent controlled. For example, in the dihydroxylation of the chiral alkene 5, the product is determined primarily by the choice of hydroxylation catalyst, although there is some improvement in the diastereoselectivity with one pair. This is a case of reagent-controlled sfereoselecfion. 

Complexes of the type [Ir(bzn)(cod)(L)](C104) (bzn = benzonitrile L = tricyclohexylphosphine, neomenthyldiphenylphosphine) catalyze the homogeneous hydrogenation of tetrasubstituted prochiral amido alkenes R R C=CR N. Under very mild conditions, the catalysis occurs for N = NHCOR, R = COjMe R = R = Me, R" = Me, Ph R = Me, R- = Ph, R = Me, Ph R = Ph, R = Me, R = Ph. [Ir(cod)(PCy3)(py)](PFg) serves as a catalyst in the hydroxyl-directed hydrogenation of cyclic and acyclic alkenic alcohols, wherein the reaction shows diastereoselectivity dependent on catalyst substrate stoichiometry. Park el have noted that the iridium(I)... 

A similar strategy utilizing 8-keto esters provided very high diastereoselectivities in the ketyl-alkene coupling process. In these examples, chelation control about the developing hydroxyl and carboxylate stereocenters was the source of the high diastere-oselectivity achieved (eq 23) ... 

Ketone-Alkene Coupling Reactions. Ketyl radicals derived fromreduction of ketones or aldehydes with Sml2 may be coupled both inter- and intramolecularly to a variety of alkenic species. Excellent diastereoselectivities are achieved with intramolecular coupling of the ketyl radical with Q ,/3-unsaturated esters. In the following example, ketone-alkene cyclization took place in a stereocontrolled manner established by chelation of the resulting Sm(III) species with the hydroxyl group incorporated in the substrate (eq 22). ... 

If an alkene has a hydroxyl (or other functional group capable of donating a proton in a hydrogen bonding interaction) in the allylic position, that group can affect the stereochemistry of the epoxide product. For example, reaction of cyclic allylic alcohols produces a 10 1 ratio of product with the epoxide cis to the alcohol fimction (equation 9.55) relative to the trans product. This diastereoselectivity has been attributed to hydrc en bonding in the transition structure for the epoxidation (Figure... 

Anchoring the allyl sulfoxide at an exocyclic carbon, with the alkene situated within a stereochemically defined ring, provides the opportunity for diastereoselective installation of a hydroxyl group on the ring, along with an exocyclic olefin that serves as a handle for further elaboration. Ohfune and Shinada applied this Mislow-Evans-based strategy effectively in... 

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