Addition reactions dihydroxylation

The completion of the synthesis of the polyol glycoside subunit 7 requires construction of the fully substituted stereocenter at C-10 and a stereocontrolled dihydroxylation of the C3-C4 geminally-disub-stituted olefin (see Scheme 10). The action of methyllithium on Af-methoxy-Af-methylamide 50) furnishes a methyl ketone which is subsequently converted into intermediate 10 through oxidative removal of the /j-methoxybenzyl protecting group with DDQ. Intermediate 10 is produced in an overall yield of 83 % from 50) , and is a suitable substrate for an a-chelation-controlled carbonyl addition reaction.18 When intermediate 10 is exposed to three equivalents of... 

Tetrabutylammonium fluoride, 286 Titanium(IV) chloride-Diethylalumi-num chloride, 309 Vinylene carbonate, 342 Dihydroxylation (see Addition reactions to carbon-carbon multiple bonds) Dimerization (see Coupling reactions) Displacement reactions (see Substitution reactions)... 

Chiral Auxiliary for Asymmetric Induction. Numerous derivatives of (—)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter- and intramolecular Diels-Alder reactions, dihydroxylations, and intramolecular ene reactions of a,p-unsaturated 8-phenylmenthol esters. These reactions usually proceed in moderate to good yield with high diastereofacial selectivity. a-Keto esters of 8-phenylmenthol (see 8-Phenylmenthyl Pyruvate) have been used for asymmetric addition to the keto group, as well as for asymmetric [2 -F 2] photoadditions and nucleophilic alkylation. Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity. Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone and Diels-Alder cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations and enantiose-lective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%. ... 

Eyrisch, O, Sinerius, G, Fessner, W-D, Eacile enzymic de novo synthesis and NMR spectroscopic characterization of D-tagatose 1,6-bisphosphate, Carbohydr. Res., 238, 287-306, 1993. Henderson, I, Sharpless, KB, Wong, C-H, Synthesis of carbohydrates via tandem use of the osmium-catalyzed asymmetric dihydroxylation and enzyme-catalyzed aldol addition reactions, J. Am. Chem. Soc., 116, 558-561, 1994. 

The discussion about the possible formation of metalla-2-oxetanes in transition metal-mediated oxidation reactions began with the ground breaking work of Sharpless in the field of enantioselective dihydroxylation of olefins with osmium tetraoxide using cinchona alkaloids as ligands [6]. The transfer of the stereochemical information of the chiral ligand to the substrate was explained by Sharpless with a two-step mechanism for the addition reaction, which should occur rather than a concerted [3+2] addition as originally proposed [110] (Fig. 15). 

Alkenes are very susceptible to electrophilic addition reactions, which with appropriate sources of oxygen lead to epoxidation and 1,2-dihydroxylation products. 

Dihydroxylation is an important oxidative addition reaction of alkenes. 

By applying the same postglycosylation/deprotection reaction sequence on tetrasaccharide 94, the remaining cleistetroside-5 was prepared in three steps. In addition, the revised route was also used to prepare two previously unknown analogs, cleistetroside-9 and -10. This was accomplished in a range of one to three steps by modular application of the postglycosylation reactions (dihydroxylation, acylation, and chloro-acylation) (Scheme 1.17). 

Moving forward from 59, six steps were required to convert this compound to 60. Vicinal dihydroxylation of the olefin was followed by oxidative cleavage of the intermediate diol using lead tetraacetate. Reductive amina-tion of the resulting aldehyde with methylamine, followed by acylation of the intermediate secondary amine gave the desired carbamate. Swern oxidation of the secondary alcohol, followed by enol ether formation gave 60. Elimination of -toluenesulfinic acid from 60 provided 61. Oxidation of this dienol ether to dienone 62 was followed by release of the secondary amine, followed by a conjugate addition reaction to establish the critical C-N bond. The remainder of the synthesis followed known chemistry. The mixture of enones 63 was converted to codeinone (35), codeine (3) and then morphine (1). 

In addition to dihydroxylations, Donohoe and coworkers have also used aminohydroxylation of 1,5-dienes to synthesize tetrahydrofuran substrates [58]. As in the dihydroxylation/cyclization sequence, they either employed a one-pot or a two-pot protocol. An example of the one-pot reaction is illustrated in Scheme 52. Exposure of ( , )-diene 195 to aminohydroxylation conditions efficiently gave 2,5-cis-tetrahydrofuran 196. Based on the proposed mechanism for the reaction, it is not surprising that the reaction of ( ,Z)-diene 197 gave diastereomeric 2,5-c/s-tetrahydrofuran 198 in 90 % yield. The aminohydroxylation... 

This chapter introduces several stereospecific addition reactions. Some of them occur exclusively via a syn addition (such as hydrogenation or hydroboration-oxidation), while others occur exclusively via an anti addition (such as bromination or halohydrin formation). When drawing the products of a stereoscpecific addition reaction, be careful to avoid drawing a wedge or a dash on a location that is not a chirality center. For example, consider the following syn dihydroxylation. In such a case, it is tempting for students to draw the products as if they have two chirality centers, like this ... 

Another important reaction associated with the name of Sharpless is the so-called Sharpless dihydroxylation i.e. the asymmetric dihydroxylation of alkenes upon treatment with osmium tetroxide in the presence of a cinchona alkaloid, such as dihydroquinine, dihydroquinidine or derivatives thereof, as the chiral ligand. This reaction is of wide applicability for the enantioselective dihydroxylation of alkenes, since it does not require additional functional groups in the substrate molecule ... 

The iyn-preference of 105b and 105c is similar to those observed in the reduction of the related ketones, 34 and in the epoxidation and dihydroxylation of the related olefins 71 [104]. Although the trajectories of the attacking reagents are considered to be different in these reactions [83-87, 170, 171], all three types of reactions favor iyn-addition, which excludes a predominant role of divergent trajectories in these dibenzobicyclic systems. 

In addition, also nonheme iron catalysts containing BPMEN 1 and TPA 2 as ligands are known to activate hydrogen peroxide for the epoxidation of olefins (Scheme 1) [20-26]. More recently, especially Que and coworkers were able to improve the catalyst productivity to nearly quantitative conversion of the alkene by using an acetonitrile/acetic acid solution [27-29]. The carboxylic acid is required to increase the efficiency of the reaction and the epoxide/diol product ratio. The competitive dihydroxylation reaction suggested the participation of different active species in these oxidations (Scheme 2). 

Entry 10 was used in conjunction with dihydroxylation in the enantiospecific synthesis of polyols. Entry 11 illustrates the use of SnCl2 with a protected polypropionate. Entries 12 and 13 result in the formation of lactones, after MgBr2-catalyzed additions to heterocyclic aldehyde having ester substituents. The stereochemistry of both of these reactions is consistent with approach to a chelate involving the aldehyde oxygen and oxazoline oxygen. 

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