Dihydroxylation/oxidative cleavage

L-Hamamelose, which is used as a starting material for the synthesis of potential glycosidase inhibitors, was also synthesized via dihydroxylation/oxidative cleavage/reduction (eq 78). ... 

The next key step, the second dihydroxylation, was deferred until the lactone 82 had been formed from compound 80 (Scheme 20). This tactic would alleviate some of the steric hindrance around the C3-C4 double bond, and would create a cyclic molecule which was predicted to have a greater diastereofacial bias. The lactone can be made by first protecting the diol 80 as the acetonide 81 (88 % yield), followed by oxidative cleavage of the two PMB groups with DDQ (86% yield).43 Dihydroxylation of 82 with the standard Upjohn conditions17 furnishes, not unexpectedly, a quantitative yield of the triol 84 as a single diastereoisomer. The triol 84 is presumably fashioned from the initially formed triol 83 by a spontaneous translactonization (see Scheme 20), an event which proved to be a substantial piece of luck, as it simultaneously freed the C-8 hydroxyl from the lactone and protected the C-3 hydroxyl in the alcohol oxidation state. 

Oxidative cleavage of the olefin is accomplished by the method of ijemieux-Johnson.12 The process begins with dihydroxylation of the double bond using osmium tetroxide (see Chapter 3)T leading to a cis diol and osmium(VI) oxide. The added periodate has two functions first, it reoxidizes the osmium(VI) species to os-mium(VIII), but it also cleaves the glycol oxidatively to an aldehyde. This is the reason for utilizing several equivalents of periodate. The periodate is in turn reduced from the +VH to the +V oxidation state. 

The alkylation products are synthetically useful because simple subsequent transformations furnishes precursors of important natural products as illustrated in Scheme 8E.23. Simple oxidative cleavage of allylic phthalimide 45 generates protected (5)-2-aminopimelic acid, whose dipeptide derivatives have shown antibiotic activity. The esterification via deracemization protocol is not limited to the use of bulky pivalic acid. The alkylation with sterically less hindered propionic acid also occurs with high enantioselectivity to give allylic ester 116, which has been utilized as an intermediate towards the antitumor agent phyllanthocin and the insect sex excitant periplanone. Dihydroxylation of the enantiopure allylic sulfone gives diol 117 with complete diastereoselectivity. Upon further transformation, the structurally versatile y-hydroxy-a,(f-un-saturated sulfone 118 is readily obtained enantiomerically pure. 

Os04-mediated dihydroxylation of 59 followed by an oxidative cleavage of the formed diol with NaI04 gave the aldehyde, which was decarbonylated with RhCl(PPh3)3 to yield 8-methyl derivative 60 (06OBC1587). Wacker oxidation of 59 provided 8-(2-oxopropyl) derivative 61. 

The cis-vic-Dihydroxylation of Alkenes No Oxidative Cleavage, but an Important Prelude... 

Alkenes can he dihydroxylated cw-selectively by reaction with a stoichiometric amount of N-methylmorpholine-jV-oxide (NMO), a catalytic amount of a suitable Os(VIII) reagent, and some water. From a preparative point of view, this reaction is closely related to oxidative cleavages, and for this reason it is introduced now (Figure 17.19). 

A Diels-Alder approach to varenicline was recently published by Dr. Reddy s Laboratories. Entry to a key bicyclic intermediate is achieved by an iodide-catalyzed Diels-Alder reaction of tetrabromo dimethyl pyrazine (47) with excess norbomadiene. Dihydroxylation of 48, oxidative cleavage, and reductive amination prepares N-p-methoxybenzyl varenicline (50), which is deprotected under transfer hydrogenation conditions to give varenicline (1) in 10% yield for the sequence.47 This approach continues the theme of building the piperidine of 1 through olefin oxidative cleavage and reductive amination, but by doing so late in the sequence however, the approach... 

Mechanism 8-10 Acid-Catalyzed Opening of Epoxides 362 8-14 Syn Dihydroxylation of Alkenes 364 8-15 Oxidative Cleavage of Alkenes 366 8-16 Polymerization of Alkenes 369 8-17 Olefin Metathesis 373... 

Oxidative cleavage of the double bond in 168 (Scheme 33, Section 14.10.6.3) by ozonolysis was unsuccessful, while its dihydroxylation and treatment of resulting diol with lead(iv) acetate gave diketone 169 <1999T7471>. Ozonolysis of isopropyl 1,3,4,5,6,7-hexahydro-l-methylisobenzofuran-l-carboxylate 131 (Scheme 23, Section 14.10.5.6.3) proceeded smoothly and led to the corresponding oxonine carboxylate 132 <20020L3059>. 

The oxidative cleavage of norbornylene was achieved using the two-step procedure consisting of the Sharpless dihydroxylation and NaI04 oxidation of the resulting diols and is discussed (1). 

Various substrates such as allyl alcohols, a,y3-unsaturated carbonyl compounds, and enol ethers undergo oxidative cleavage to afford the corresponding carbonyl compounds (Eqs. 3.35-3.37) [69-71], cis-Dihydroxylation occurs selectively, when the... 

As an oxometal component, osmium tetroxide is the most reliable reagent on the laboratory scale to produce c/s-diols. Ruthenium tetroxide in the presence of NaI04 effects oxidative cleavage of olefins [4], but has been successfully employed for so-called lightning dihydroxylation reactions using a two-phase medium [6]. 

Dihydroxylation of the terminal alkene of 90, followed by oxidative cleavage to the aldehyde allowed the authors to isolate compound 86 in an enantiomerically pure form. However, the low yielding (24%) bromoetherification step led the authors to search for a more efficient method. 

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